Publications by authors named "Jianmin Xiao"

29 Publications

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Highly sensitive T-Tdual-mode MRI probe based on ultra-small gadolinium oxide-decorated iron oxide nanocrystals.

Biomed Mater 2021 Mar 16. Epub 2021 Mar 16.

Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, CHINA.

Single-mode magnetic resonance imaging (MRI) contrast agents (CAs) in clinical settings are easily disturbed by calcification, bleeding, and adipose signals, which result in inaccurate diagnoses. In this study, we developed a highly efficient T-Tdual-mode MRI CA using an ultra-small gadolinium oxide-decorated magnetic iron oxide nanocrystal (GMIO). The gadolinium element could effectively alter the magnetic properties of the GMIO from soft-ferromagnetism to superparamagnetism. In addition, when the Gd/Fe ratio was 15 % (designated as GMIO-2), the GMIO-2 possessed the best superparamagnetism and highest magnetism. Subsequently, Tand Tvalues of GMIO-2 were measured through a series of turbo spin-echo images and then multi-spin echo (MSE) sequence, respectively. Based on this, Tand Trelaxivities of GMIO-2 were calculated and were the highest (r: 1.306 m Msand r: 234.5 m Ms) when compared to other groups. The cytotoxicity of GMIO-2 was negligible under a wide range of dosages, thus exhibiting excellent cell biocompatibility. Moreover, GMIO-2 could quickly diffuse into cells, leading to its effective accumulation. The systemic delivery of GMIO-2 resulted in an excellent T-Tdual-mode MRI contrast effect in kidneys, which is expected to improve the diagnosis of kidney lesions. Therefore, this work provides a promising candidate for the development of a T-Tdual-mode MRI CA.
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http://dx.doi.org/10.1088/1748-605X/abef54DOI Listing
March 2021

Long-Term Arterial Remodeling After Bioresorbable Scaffold Implantation 4-Year Follow-up of Quantitative Coronary Angiography, Histology and Optical Coherence Tomography.

Cardiovasc Eng Technol 2020 Dec 27;11(6):636-645. Epub 2020 Oct 27.

Department of Cardiology, The Dongguan Affiliated Hospital of Jinan University, Binhaiwan Central Hospital of Dongguan, Dongguan, China.

Purpose: Our previous studies have confirmed the safety and efficacy of the novel fully bioresorbable PLLA scaffold (PowerScaffold®) at 12 months implantation. In the present study, the scaffold absorption and coronary vessel remodeling at 4 years were evaluated.

Methods: After PowerScaffold® were implanted into 13 coronary arteries of 6 miniature pigs, quantitative coronary angiography (QCA) was performed at 15 days and 4 years follow-up to measure the mean lumen diameter (MLD), late lumen loss (LLL), and % stenosis of the coronary arteries. Optical coherence tomography (OCT) was performed to obtain the strut footprints at 4 years before euthanization for histological analysis. In addition, 2 PowerScaffold® were implanted into 2 miniature pigs for 2 years as supplementary data. All stented arteries were dissected and stained with HE, Masson, EVG, and Alcian blue to observe struts, cells, fibrinoid, elastin, and proteoglycans, respectively.

Results: There were no significant differences in MLD, LLL and % stenosis in stented coronary arteries between 15 days and 4 years by QCA. At 4 years, most strut sites were indiscernible and replaced by extracellular matrix and connective tissue by histology. Both strut/vessel wall interaction and strut coverage were shown 100% by OCT.

Conclusion: At 4 years, the scaffold struts were completely embedded into vessel wall and mostly replaced by regenerated tissue. There was no sign of in-stent stenosis in all stented arteries.
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http://dx.doi.org/10.1007/s13239-020-00495-7DOI Listing
December 2020

Oxygen Vacancy Defect-Induced Activity Enhancement of Gd Doping Magnetic Nanocluster for Oxygen Supplying Cancer Theranostics.

ACS Appl Mater Interfaces 2020 Aug 7;12(33):36917-36927. Epub 2020 Aug 7.

School of Pharmacy, the Key Laboratory of Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine of China, Binzhou Medical University, Yantai 264003, P. R. China.

This work finds that FeO nanoclusters can rearrange by Gd doping and then self-assemble to a hollow magnetic nanocluster (HMNC), providing larger magnetic moments to obtain an excellent MRI capability and increasing the number of oxygen vacancies in HMNC. The hollow structure makes platinum(IV) prodrugs effectively load into HMNC. Second, plenty of oxygen vacancy defects can capture oxygen molecules, enhance the catalytic activity of HMNC, and then promote intracellular ROS generation. On the basis of this, a targeting iRGD-labeled HMNC nanosystem (iHMNCPt-O) is developed through loading oxygen molecules and platinum(IV) prodrugs for chemo- and chemodynamic therapy of cancer. This nanosystem shows an excellent response ability to weak acid and GSH, which can cause a series of cascade reactions in a cell. These cascade reactions are dramatically enhanced at the intracellular ROS level, cause mitochondria and DNA damage, and then induce cancer cell death. Besides, systemic delivery of iHMNCPt-O significantly enhanced the MRI contrast signal of tumors and improved the quality of MR images, accurately diagnosing tumors. Therefore, this work provides a novel method for accelerating the Fenton-like reaction and enhancing the MRI capability and fabricates a promising "all-in-one" system to overwhelm the problems of cancer theranostic.
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http://dx.doi.org/10.1021/acsami.0c09952DOI Listing
August 2020

Effect of Cr on the Mineral Structure and Composition of Cement Clinker and Its Solidification Behavior.

Materials (Basel) 2020 Mar 26;13(7). Epub 2020 Mar 26.

College of Materials Science and Engineering, Xi'an University of Architecture and Technology, Xi'an 710055, China.

In order to reveal the solidification behavior of Cr in the cement clinker mineral phase, Si magic-angle spinning nuclear magnetic resonance, X-ray diffraction, and scanning electron microscopy with energy-dispersive X-ray spectroscopy techniques were used to analyze the morphology and composition of the cement clinker mineral phase doped with Cr. The results showed that the addition of Cr did not change the chemical environment of Si in the clinker mineral phase, and it was still an isolated silicon-oxygen tetrahedron. Cr affected the orientation of the silicon-oxygen tetrahedron and the coordination number of calcium, leading to the formation of defects in the crystal structure of the clinker mineral phase, by replacing Ca into the mineral phase lattice to form a new mineral phase CaCr(SiO). Cr acted as a stabilizer for the formation of β-CS in the clinker calcination. As the amount of Cr increased, the relative content of CS decreased and the relative content of CS increased. Further, Cr easily dissolved in CS, while it was not found in CS. This study is conducive to further research on the mechanism of heavy metal solidification in cement clinker. Furthermore, it is important to evaluate the environmental risk of heavy metals in the process of sludge disposal through cement kiln and promote the utilization of sludge resources and the sustainable development of the cement industry.
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http://dx.doi.org/10.3390/ma13071529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177747PMC
March 2020

Promoting desert biocrust formation using aquatic cyanobacteria with the aid of MOF-based nanocomposite.

Sci Total Environ 2020 Mar 20;708:134824. Epub 2019 Nov 20.

College of Environmental Science and Engineering, Donghua University, Shanghai 201620, People's Republic of China. Electronic address:

Desertification and eutrophication are two global environmental problems human beings face. Inoculating cyanobacteria to form biocrusts is considered an effective technology to inhibit desertification. The main limitation of biocrust formation is the lack of propagules and nutrients in deserts. A possible low cost source of propagules and nutrients is eutrophic water containing aquatic cyanobacteria (AC), nitrogen and phosphorus. In this study, we fabricated a network-structured nanocomposite (designated as MC) using a metal-organic framework (MOF) and carboxymethyl cellulose (CMC). MC, with a large specific surface area and numerous surface groups, had a high retention capacity for water and nutrients and good biosafety. The combination of AC-containing water (ACW) and MC could provide a suitable microenvironment in the soil, promote the growth of desert cyanobacteria (DC), formation of biocrusts and inhibition of desertification. This study provides a novel approach to simultaneously relieve desertification and eutrophication.
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http://dx.doi.org/10.1016/j.scitotenv.2019.134824DOI Listing
March 2020

Long-term clinical safety and efficacy of drug-coated balloon in the treatment of in-stent restenosis: A meta-analysis and systematic review.

Catheter Cardiovasc Interv 2020 08 12;96(2):E129-E141. Epub 2019 Nov 12.

Department of Cardiology, The Dongguan Affiliated Hospital (Dongguan 5th People's Hospital), Jinan University School of Medicine, Dongguan, China.

Objectives: The aim of this study was to evaluate the long-term clinical safety and efficacy of drug-coated balloon (DCB) in the treatment of in-stent restenosis (ISR).

Background: There is a long-term safety issue in peripheral arterial disease patients treated with paclitaxel-coated balloon, this has also raised concerns on DCB in coronary intervention.

Methods: Nine randomized controlled trials (RCTs) and nine observational studies (OSs) were included with a total of 3,782 patients (1,827 in the DCB group, 1,955 in the drug-eluting stent [DES] group) being analyzed. The primary outcome measure-major adverse cardiovascular events (MACEs), target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI), cardiac death (CD), stent thrombosis (ST), all-cause death (AD), and coronary angiography outcomes included late lumen loss (LLL), minimum luminal diameter (MLD), diameter stenosis (DS) were analyzed.

Results: DCB treatment significantly reduced the LLL (MD: -0.13; [CI -0.23 to -0.03], p = .01). No difference was found for MLD (MD: -0.1; [CI -0.24 to 0.04], p = .17) and DS% (RR = 0.98 [CI 0.80-1.20], p = .86). There was no significant difference in TLR, TVR, MI, CD, ST, AD, and the overall incidence of MACEs between the two groups up to 3 years follow-up. Subgroup analysis for different type of ISR and DES showed no significant difference in the incidence of endpoints, and there is no difference when considering RCTs or OSs only.

Conclusions: The safety and efficacy of the DCB and DES in the treatment of ISR is comparable at up to 3 years follow-up.
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http://dx.doi.org/10.1002/ccd.28572DOI Listing
August 2020

Inflammation and dysfunction in human aortic endothelial cells associated with poly-l-lactic acid degradation in vitro are alleviated by curcumin.

J Biomed Mater Res A 2019 12 9;107(12):2756-2763. Epub 2019 Sep 9.

Central Laboratory, The Dongguan Affiliated Hospital of Medical College of Jinan University, The Fifth People's Hospital of Dongguan, Dongguan, China.

Poly-l-lactic acid (PLLA) is widely used in clinic, for example, as biodegradable coronary artery stents. However, inflammatory responses in endothelial cells associated with PLLA degradation are relatively undefined. We previously reported inflammation in human aortic endothelial cells (HAEC) in vitro and in vivo. Here, we further assessed inflammatory injury, including cell migration, cell function, and inflammatory cytokines expressed in HAEC treated with PLLA and curcumin by CCK-8, wound healing assay, ELISA, and Western blot. Significant inhibition of cell migration, remarkable dysfunction, and inflammatory responses were found in HAEC treated with PLLA degradation extract, and these effects were alleviated by Cur treatment. These findings indicated that cautious evaluation of biodegradable polymers should be performed, and Cur represents a promising anti-inflammatory agent for alleviating endothelial dysfunction and inflammation caused by PLLA degradation. In addition, Cur should be further studied experimentally in in vivo experiments on animal models as a potential therapeutic to reduce thrombosis of biodegradable polymer stents.
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http://dx.doi.org/10.1002/jbm.a.36778DOI Listing
December 2019

A pH-responsive platform combining chemodynamic therapy with limotherapy for simultaneous bioimaging and synergistic cancer therapy.

Biomaterials 2019 09 5;216:119254. Epub 2019 Jun 5.

Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, PR China. Electronic address:

Chemodynamic therapy (CDT) was widely exploited for cancer therapy and expected to replace traditional anticancer drug therapies. Generally, CDT needs to combine with extra therapeutic methods for obtaining the optimal therapeutic efficacy of cancer. Herein, a multifunctional theranostic platform combing CDT with limotherapy was developed via nanoselenium (nano-Se)-coated manganese carbonate-deposited iron oxide nanoparticle (MCDION-Se). MCDION-Se could release abundant of Mn ions that catalyzed HO into hydroxyl radicals (·OH) via a Fenton-like reaction, effectively inducing the apoptosis of cancer cells. Besides, nano-Se coated onto MCDION-Se also dramatically activated superoxide dismutase (SOD) and promoted the generation of superoxide anion radicals (SOARs) in tumor tissue. Subsequently, a high content of HO was produced via SOD catalysis of SOARs, further enhancing CDT efficiency. Meanwhile, the nano-Se and Mn ions inhibited the generation of adenosine triphosphate (ATP), thus starving cancer cells. In addition, in vitro and in vivo experiments showed that MCDION-Se could effectively enhance the contrast of tumor tissue and improve the quality of magnetic resonance imaging (MRI). Overall, this work provided a nanoplatform that combined CDT with limotherapy for cancer therapy and simultaneously utilized MRI for monitoring the treatment of tumors.
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http://dx.doi.org/10.1016/j.biomaterials.2019.119254DOI Listing
September 2019

Effect of inflammation on endothelial cells induced by poly-L-lactic acid degradation in vitro and in vivo.

J Biomater Sci Polym Ed 2018 10 8;29(15):1909-1919. Epub 2018 Oct 8.

a Central Laboratory, The Dongguan Affiliated Hospital of Medical College of Jinan University , The Fifth People's Hospital of Dongguan , Dongguan , China.

As a promising candidate, biodegradable Poly-L-lactic Acid (PLLA) has been extensively used in coronary artery stents. In our previous reports, PLLA stents implanted in porcine coronary arteries showed safety without stent thrombosis. However, inflammatory responses were observed, which needed further study. In this study, human aortic endothelial cells (HAEC) were treated with different volume percentages of extract of pre-degraded PLLA (extract of PLLA) in vitro, and the cell growth curve and morphological changes were examined. The expression of inflammatory cytokines such as NF-κB, VEGF and VCAM-1 were also observed by ELISA. In addition, PLLA stent was implanted in porcine coronary artery to examine morphological changes, functional marker eNOS and inflammatory responses. The extract of PLLA caused significant growth inhibition and release of NF-κB, VEGF and VCAM-1 in HAEC with volume percentage-dependence. Although re-endothelialization and expression of eNOS was observed, expression of NF-κB and lymphocytes surrounding PLLA were also found after PLLA stents were implanted in the artery. This study demonstrated the effects of inflammation on endothelial cells induced by PLLA degradation in vitro and showed the inflammation in vivo, suggesting that anti-inflammatory strategy is necessary for PLLA stent implantation in the artery.
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http://dx.doi.org/10.1080/09205063.2018.1517858DOI Listing
October 2018

Fabricating High-Performance T-Weighted Contrast Agents via Adjusting Composition and Size of Nanomagnetic Iron Oxide.

ACS Appl Mater Interfaces 2018 Feb 13;10(8):7003-7011. Epub 2018 Feb 13.

Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences , Hefei 230031, People's Republic of China.

Magnetic relaxation switch demonstrated that the aggregated nanomagnetic iron oxide (NMIO) nanocrystal possessed a lower T value and better relaxivity compared with monodispersed NMIO nanocrystal. However, we found that NMIO nanoclusters (NMIONCs) showed a different magnetic resonance (MR) imaging property in comparison with NMIO nanocrystals. Herein, three types of NMIONCs were used to explore the effects of size and compositions on the variations of magnetism and MR contrast ability. It was found that the transverse relaxation rate (r) of NMIONCs depended on the contact area between particles and water molecules. The smaller size and higher solubility could carry out higher contact area between NMIONCs and water molecules. Therefore, the monodispersed NMIONC showed a better T contrast ability in comparison with the aggregated NMIONC. In addition, for NMIONCs with the same composition, the magnetism and contrast ability gradually increased with the particle size decreasing. In vivo, NMIONCs that possessed the best solubility and the smallest size showed the most effective MR contrast effect for the liver region of mice. As a result, the size and composition of NMIONCs played important roles for enhancing contrast behavior. This study provides a new idea to develop high-performance T contrast agents by modulating the size and composition of particles.
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http://dx.doi.org/10.1021/acsami.8b00428DOI Listing
February 2018

Functional Analyses of a Novel CITED2 Nonsynonymous Mutation in Chinese Tibetan Patients with Congenital Heart Disease.

Pediatr Cardiol 2017 Aug 8;38(6):1226-1231. Epub 2017 Jul 8.

Qinghai High Altitude Medical Research Institute, No.7, Zhuanchang Road, West District, Xining, 810012, China.

CITED2 gene is an important cardiac transcription factor that plays a fundamental role in the formation and development of embryonic cardiovascular. Previous studies have showed that knock-out of CITED2 in mice might result in various cardiac malformations. However, the mechanisms of CITED2 mutation on congenital heart disease (CHD) in Chinese Tibetan population are still poorly understood. In the present study, 187 unrelated Tibetan patients with CHD and 200 unrelated Tibetan healthy controls were screened for variants in the CITED2 gene; we subsequently identified one potential disease-causing mutation p.G143A in a 6-year-old girl with PDA and functional analyses of the mutation were carried out. Our study showed that the novel mutation of CITED2 significantly enhanced the expression activity of vascular endothelial growth factor (VEGF) under the role of co-receptor hypoxia inducible factor 1-aipha (HIF-1A), which is closely related with embryonic cardiac development. As a result, CITED2 gene mutation may play a significant role in the development of pediatric congenital heart disease.
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http://dx.doi.org/10.1007/s00246-017-1649-yDOI Listing
August 2017

[ARTICLE WITHDRAWN] Dexmedetomidine Inhibits Osteosarcoma Cell Proliferation and Migration, and Promotes Apoptosis by Regulating miR-520a-3p.

Oncol Res 2018 04 23;26(3):495-502. Epub 2017 Jun 23.

Department of Anesthesiology, Ningjin People's Hospital, Ningjin, Shandong, P.R. China.

THIS ARTICLE WAS WITHDRAWN BY THE PUBLISHERS IN NOVEMBER 2020.
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http://dx.doi.org/10.3727/096504017X14982578608217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844699PMC
April 2018

12-Month Coronary Angiography, Intravascular Ultrasound and Histology Evaluation of a Novel Fully Bioabsorbable Poly-L-Lactic Acid/Amorphous Calcium Phosphate Scaffolds in Porcine Coronary Arteries.

J Biomed Nanotechnol 2016 Apr;12(4):743-52

Our previous studies have confirmed the superior biocompatibility of the poly-L-lactic acid/amorphous calcium phosphate (PLLA/ACP) scaffolds (PowerScaffold) compared to PLLA scaffolds and their similar 6-month radial strength compared with TAXUS stents. In order to conduct further dynamic observations on the performance of the PowerScaffold after 12-month implantation compared with the TAXUS stents. Twenty PowerScaffold and 20 TAXUS were implanted in porcine coronary arteries. At 12-month follow-up, Quantitative Coronary Angiography showed that the stent reference vessel diameter (3.19 ± 0.25 mm vs. 2.75 ± 0.22 mm, p < 0.05), the mean lumen diameter (3.07 ± 0.22 mm vs. 2.70 ± 0.17 mm, p < 0.05) and the late lumen gain (0.45 ± 0.07 mm vs. 0.06 ± 0.06 mm, p < 0.01) were all significantly greater with the PowerScaffold than the TAXUS. As well, Intravascular Ultrasound showed the stent reference vessel area (7.74 ± 0.48 mm2 vs. 6.96 ± 0.51 mm2, p < 0.05), the mean stent area (7.49 ± 0.46 mm2 vs. 6.53 ± 0.47 mm2, p < 0.05) and the mean lumen area (7.22 ± 0.50 mm2 vs. 6.00 ± 0.48 mm2, p < 0.01) were all significantly greater with the PowerScaffold than the TAXUS. The luminal patency rate of the PowerScaffold significantly increased from 72.45 ± 6.84% at 1 month to 93.54 ± 8.15% at 12 months (p < 0.01) while the TAXUS stents were associated with a non-significant decreasing trend (89.44 ± 8.44% vs. 86.53 ± 8.22%). Pathology indicated the average thickness of the struts degraded by 14.25 ± 3.04 μm at 1 month, 23.39 ± 2.45 μm at 6 months and 35.54 ± 2.20 μm at 12 months. Immunohistochemical examination showed that the expression of inflammatory factors NF-κB gradually decreased from 1-month to 12-month (36.79 ± 4.78 vs. 5.79 ± 2.85, P < 0.01). As the late lumen gain of arteries implanted with the PowerScaffold increases over time with the growth of vessels, it effectively reverse the late vascular negative remodeling observed with the TAXUS stents, providing a better option for lumen restoration treatment in clinical practice.
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http://dx.doi.org/10.1166/jbn.2016.2241DOI Listing
April 2016

Congenital Heart Disease in Local and Migrant Elementary Schoolchildren in Dongguan, China.

Am J Cardiol 2016 Feb 18;117(3):461-4. Epub 2015 Nov 18.

Department of Cardiology, the Dongguan Affiliated Hospital of Medical College of Jinan University, the Fifth People's Hospital of Dongguan (also called Taiping People's Hospital of Dongguan), Guangdong, China.

The aim of this study was to determine the prevalence and treated status of congenital heart disease (CHD) in elementary schoolchildren and facilitate the long-term planning of health care, resource allocation, and development of targeted primary prevention strategies. From November 2011 to November 2012, 540,574 schoolchildren from 449 elementary schools were screened for CHD by trained doctors in Dongguan City. The schoolchildren who were suspected to have CHD were referred to a pediatric cardiologist and/or an echocardiographist for complete evaluation. Of them, 214,634 (39.7%) were local children and 325,940 (60.3%) were migrant children. The total prevalence of CHD was 2.14‰, and there was a significant difference (p <0.05) of the CHD prevalence between local (1.97‰) and migrant children (2.26‰). The treatment rates of CHD in local children and in migrant children were 63.51% and 47.21%, respectively (p <0.01). The commonest CHD was ventricular septal defect (43.13%), followed by atrial septal defect (25.84%) and patent ductus arteriosus (12.79%). With respect to gender, CHD was equally distributed between men and women. In conclusion, social, economic, and environmental risk factors that affect health of migrant children with CHD call for more attention from health policy makers and researchers in contemporary China. Efforts should be made to increase public health investment, establish health care manage system for children from migrant families, and increase the parents' awareness of preventing the CHD.
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http://dx.doi.org/10.1016/j.amjcard.2015.10.061DOI Listing
February 2016

6-Month Follow-Up of a Novel Biodegradable Drug-Eluting Stent Composed of Poly-L-Lactic Acid and Amorphous Calcium Phosphate Nanoparticles in Porcine Coronary Artery.

J Biomed Nanotechnol 2015 Oct;11(10):1819-25

Rationale: We reported previously, in porcine coronary arteries, that the novel biodegradable PowerStent Absorb paclitaxel-eluting stent had improved and sustained structural strength and functional performance at one month post-implantation.

Objective: To report the stent performance at 6-month follow-up.

Methods And Results: Six PowerStent Absorb and six TAXUS stents were randomly implanted in the left anterior descending and right coronary arteries of six Tibet miniature pigs. Quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) images were obtained at the time of implantation (T0) and at 6 months (T6). Two animals were sacrificed at T6 for histopathological evaluation. At T6, QCA showed that the mean luminal vascular diameter (mLD) between the PowerStent and the TAXUS stents were similar (2.36 ± 0.38 vs. 2.61 ± 0.31, respectively). Based on the IVUS analysis, the mLD and the mean lumen cross-sectional area (mCSA) in the PowerStent-treated arteries were similar between T0 and T6 (mLD: 2.74 ± 0.13 vs. 2.70 ± 0.20 and mCSA: 6.81 ± 0.62 mm2 vs. 6.68 ± 0.94 mm2). Histopathology showed that the PowerStent stents were well apposed to the vessel wall with no recoil, strut fracture and thrombus formation. The stents were fully covered with a layer of endothelial cells.

Conclusions: At six-month post-implantation, the PowerStent Absorb stents maintained their structural strength and functional performance. The development of restenosis was controlled, no stent thrombosis was observed and the stents were fully re-endothelialized. These results suggest the PowerStent Absorb stent is safe and effective for up to 6 months when implanted in porcine coronary arteries.
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http://dx.doi.org/10.1166/jbn.2015.2102DOI Listing
October 2015

ATG16L1 phosphorylation is oppositely regulated by CSNK2/casein kinase 2 and PPP1/protein phosphatase 1 which determines the fate of cardiomyocytes during hypoxia/reoxygenation.

Autophagy 2015 ;11(8):1308-25

a Department of Cardiology ; Affiliated Baoan Hospital of Southern Medical University ; Shenzhen , China.

Recent studies have shown that the phosphorylation and dephosphorylation of ULK1 and ATG13 are related to autophagy activity. Although ATG16L1 is absolutely required for autophagy induction by affecting the formation of autophagosomes, the post-translational modification of ATG16L1 remains elusive. Here, we explored the regulatory mechanism and role of ATG16L1 phosphorylation for autophagy induction in cardiomyocytes. We showed that ATG16L1 was a phosphoprotein, because phosphorylation of ATG16L1 was detected in rat cardiomyocytes during hypoxia/reoxygenation (H/R). We not only demonstrated that CSNK2 (casein kinase 2) phosphorylated ATG16L1, but also identified the highly conserved Ser139 as the critical phosphorylation residue for CSNK2. We further established that ATG16L1 associated with the ATG12-ATG5 complex in a Ser139 phosphorylation-dependent manner. In agreement with this finding, CSNK2 inhibitor disrupted the ATG12-ATG5-ATG16L1 complex. Importantly, phosphorylation of ATG16L1 on Ser139 was responsible for H/R-induced autophagy in cardiomyocytes, which protects cardiomyocytes from apoptosis. Conversely, we determined that wild-type PPP1 (protein phosphatase 1), but not the inactive mutant, associated with ATG16L1 and antagonized CSNK2-mediated phosphorylation of ATG16L1. Interestingly, one RVxF consensus site for PPP1 binding in the C-terminal tail of ATG16L1 was identified; mutation of this site disrupted its association with ATG16L1. Notably, CSNK2 also associated with PPP1, but ATG16L1 depletion impaired the interaction between CSNK2 and PPP1. Collectively, these data identify ATG16L1 as a bona fide physiological CSNK2 and PPP1 substrate, which reveals a novel molecular link from CSNK2 to activation of the autophagy-specific ATG12-ATG5-ATG16L1 complex and autophagy induction.
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http://dx.doi.org/10.1080/15548627.2015.1060386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590681PMC
June 2016

Prevalence and clinical significance of cardiac murmurs in schoolchildren.

Arch Dis Child 2015 Nov 12;100(11):1028-31. Epub 2015 Jun 12.

Department of Cardiology, The Dongguan Affiliated Hospital of Medical College of Jinan University, the Fifth People's Hospital of Dongguan (also called Taiping People's Hospital of Dongguan), Dongguan, Guangdong, China.

Objective: To determine the prevalence and clinical significance of heart murmurs detected during heart disease screening among apparently healthy schoolchildren.

Design: Cross-sectional study.

Setting: 32 elementary schools in Dongguan City of China.

Patients: 81,213 schoolchildren aged 5-13 years from different elementary schools.

Main Outcome Measures: The prevalence and clinical significance of heart murmurs among schoolchildren.

Results: Murmurs were detected in 2193 schoolchildren (2.7%), of whom 215 had a structural heart disease (SHD). Of patients who had SHD, 198 children had congenital heart disease (CHD), 12 had mitral valve prolapse and 5 had rheumatic heart disease. In patients who had CHD, the most common diagnosis was a ventricular septal defect. With respect to sex, SHDs were equally distributed between males and females. Of the schoolchildren who had a murmur, 1797 (81.9%) had a murmur with the loudness of grade 1 or 2 and 396 (18.1%) had a murmur with the loudness of grades 3-6. The prevalence of SHD fell significantly with increasing age.

Conclusions: The study suggested that apparently healthy schoolchildren with grade ≤2 cardiac murmurs are least likely to have underlying SHD, especially in those aged ≥10 years. However, echocardiography should be performed in younger schoolchildren with cardiac murmur grade ≥3.
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http://dx.doi.org/10.1136/archdischild-2014-307819DOI Listing
November 2015

Role of Cys³⁶⁰² in the function and regulation of the cardiac ryanodine receptor.

Biochem J 2015 Apr;467(1):177-90

*The Libin Cardiovascular Institute of Alberta, Department of Physiology and Pharmacology and Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada.

The cardiac Ca²⁺ release channel [ryanodine receptor type 2 (RyR2)] is modulated by thiol reactive agents, but the molecular basis of RyR2 modulation by thiol reagents is poorly understood. Cys³⁶³⁵ in the skeletal muscle RyR1 is one of the most hyper-reactive thiols and is important for the redox and calmodulin (CaM) regulation of the RyR1 channel. However, little is known about the role of the corresponding cysteine residue in RyR2 (Cys³⁶⁰²) in the function and regulation of the RyR2 channel. In the present study, we assessed the impact of mutating Cys³⁶⁰² (C³⁶⁰²A) on store overload-induced Ca²⁺ release (SOICR) and the regulation of RyR2 by thiol reagents and CaM. We found that the C³⁶⁰²A mutation suppressed SOICR by raising the activation threshold and delayed the termination of Ca²⁺ release by reducing the termination threshold. As a result, C³⁶⁰²A markedly increased the fractional Ca²⁺ release. Furthermore, the C³⁶⁰²A mutation diminished the inhibitory effect of N-ethylmaleimide on Ca²⁺ release, but it had no effect on the stimulatory action of 4,4'-dithiodipyridine (DTDP) on Ca²⁺ release. In addition, Cys³⁶⁰² mutations (C³⁶⁰²A or C³⁶⁰²R) did not abolish the effect of CaM on Ca²⁺-release termination. Therefore, RyR2-Cys³⁶⁰² is a major site mediating the action of thiol alkylating agent N-ethylmaleimide, but not the action of the oxidant DTDP. Our data also indicate that residue Cys³⁶⁰² plays an important role in the activation and termination of Ca²⁺ release, but it is not essential for CaM regulation of RyR2.
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http://dx.doi.org/10.1042/BJ20141263DOI Listing
April 2015

A novel variation of GDF3 in Chinese Han children with a broad phenotypic spectrum of non-syndromic CHDs.

Cardiol Young 2015 Oct 5;25(7):1263-7. Epub 2014 Nov 5.

3Center for Genetics,National Research Institute for Family Planning,Beijing,China.

Background: The GDF3 gene plays a fundamental role in embryonic morphogenesis. Recent studies have indicated that GDF3 plays a previously unrecognised role in cardiovascular system development. Non-syndromic CHDs might be a clinically isolated manifestation of GDF3 mutations. The purpose of the present study was to identify potential pathological mutations in the GDF3 gene in Chinese children with non-syndromic CHDs, and to gain insight into the aetiology of non-syndromic CHDs.

Methods: A total of 200 non-syndromic CHDs patients and 202 normal control patients were sampled. There were two exons of the human GDF3 gene amplified using polymerase chain reaction. The polymerase chain reaction products were purified and directly sequenced.

Results: One missense mutation (c.C635T, p.Ser212 Leu, phenotype: isolated muscular ventricular septal defect) was found that has not been reported previously.

Conclusions: To the best of our knowledge, this is the first study to investigate the role of the GDF3 gene in non-syndromic CHDs. Our results expand the spectrum of mutations associated with CHDs and first suggest the potentially disease-related GDF3 gene variant in the pathogenesis of CHDs.
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http://dx.doi.org/10.1017/S1047951114002170DOI Listing
October 2015

Novel biodegradable drug-eluting stent composed of poly-L-lactic acid and amorphous calcium phosphate nanoparticles demonstrates improved structural and functional performance for coronary artery disease.

J Biomed Nanotechnol 2014 Jul;10(7):1194-204

Bioabsorbable drug-eluting stents (BDES) offer multiple advantages over a permanent bare metal stent (BMS) for coronary artery disease (CAD). However, current BDES remains two major issues: inferior radial strength and biocompatibility. PowerStent Absorb BDES, fabricated by co-formulating amorphous calcium phosphate (ACP) nanoparticles with poly-L-lactic acid (PLLA/ACP, 98/2, w/w) and 2% Paclitaxel (PAX, w/w) was designed to address these issues. Two cohorts of 6 miniature pigs were each implanted with PLLA/PAX (control, 2% PAX, w/w) or PowerStent Absorb BDES. After 1 month in-vivo study, histological analyses showed significantly reduced restenosis in the PowerStent Absorb BDES cohort relative to the control cohort (44.49 +/- 410.49% vs. 64.47 +/- 16.2%, p < 0.05). Stent recoil (21.57 +/- 5.36% vs. 33.81 +/- 11.49, P < 0.05) and inflammation (3.01 +/- 0.62 vs. 4.07 +/- 0.86, P < 0.01) were also obviously decreased. From in-vitro studies, PLLA/ACP/PAX stent tube maintained significantly greater radial strength than control group during 6 months in-vitro degradation (PLLA/ACP/PAX vs. PLLA/PAX: before hydrolysis: 82.4 +/- 1.9 N vs.74.8 +/- 3.8 N; 6 weeks: 73.9 +/- 1.8 N vs. 68.0 +/- 5.3 N; 3 months: 73.5 +/- 3.4 N vs.67.2 +/- 3.8 N; 6 months: 56.3 +/- 8.1 N vs. 57.5 +/- 4.9 N). Moreover, ACP facilitated the hydrolytic degradation of PLLA compared with control one (62.6% vs. 49.8%), meanwhile, it also increased the crystallinity of PLLA (58.4% vs. 50.7%) at 6 months. From SEM observations, ACP created nanometer pores that enlarge gradually to a micrometer scale as degradation proceeds. The changes of the porosity may result in greatly promoting re-endothelialization.
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http://dx.doi.org/10.1166/jbn.2014.1868DOI Listing
July 2014

Carvedilol analogue inhibits triggered activities evoked by both early and delayed afterdepolarizations.

Heart Rhythm 2013 Jan 14;10(1):101-7. Epub 2012 Sep 14.

Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Background: Carvedilol and its analogues suppress delayed afterdepolarizations (DADs) and catecholaminergic polymorphic ventricular tachycardias by direct action on the cardiac ryanodine receptor type 2 (RyR2).

Objective: To test a hypothesis that carvedilol analogue may also prevent triggered activities (TAs) through the suppression of early afterdepolarizations (EADs).

Methods: Intracellular Ca(2+) and membrane voltage were simultaneously recorded by using optical mapping technique in Langendorff-perfused mouse and rabbit hearts to study the effect of carvedilol analogue VK-II-36, which does not have significant beta-blocking effects.

Results: Spontaneous intracellular Ca(2+) elevations (SCaEs) during diastole were induced by rapid ventricular pacing and isoproterenol infusion in intact rabbit ventricles. Systolic and diastolic SCaEs were simultaneously noted in Langendorff-perfused RyR2 R4496(+/-) mouse hearts after creating atrioventricular block. VK-II-36 effectively suppressed SCaEs and eliminated TAs observed in both mouse and rabbit ventricles. We tested the effect of VK-II-36 on EADs by using a rabbit model of acquired long QT syndrome, in which phase 2 and phase 3 EADs were observed in association with systolic SCaEs. VK-II-36 abolished the systolic SCaEs and phase 2 EADs, and greatly decreased the dispersion of repolarization and the amplitude of phase 3 EADs. VK-II-36 completely prevented EAD-mediated TAs in all ventricles studied.

Conclusions: A carvedilol analogue, VK-II-36, inhibits ventricular tachyarrhythmias in intact mouse and rabbit ventricles by the suppression of SCaEs, independent of beta-blocking activity. The RyR2 may be a potential target for treating focal ventricular arrhythmias triggered by either EADs or DADs.
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http://dx.doi.org/10.1016/j.hrthm.2012.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3534812PMC
January 2013

Effect of oxidative stress on ventricular arrhythmia in rabbits with adriamycin-induced cardiomyopathy.

J Huazhong Univ Sci Technolog Med Sci 2012 Jun 9;32(3):334-339. Epub 2012 Jun 9.

Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

The purpose of the present study was to examine the effects of oxidative stress on ventricular arrhythmias in rabbits with adriamycin-induced cardiomyopathy and the relationship between oxidative stress and ventricular arrhythmia. Forty Japanese white rabbits were randomly divided into four groups (n=10 in each): control group, metoprolol (a selective β1 receptor blocker) group, carvedilol (a nonselective β blocker/α-1 blocker) group and adriamycin group. Models of adriamycin-induced cardiomyopathy were established by intravenously injecting adriamycin hydrochloride (1 mg/kg) to rabbits via the auri-edge vein twice a week for 8 weeks in the adriamycin, metoprolol and carvedilol groups. Rabbits in the control group were given equal volume of saline through the auri-edge vein. Rabbits in the metoprolol and carvedilol groups were then intragastrically administrated metoprolol (5 mg/kg/d) and carvedilol (5 mg/kg/d) respectively for 2 months, while those in the adriamycin and control groups were treated with equal volume of saline in the same manner as in the metroprolol and carvedilol groups. Left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were measured by echocardiography. Plasma levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), malondialdehyde (MAD) and superoxide dismutase (SOD) were detected. The left ventricular wedge preparations were perfused with Tyrode's solution. The transmural electrocardiogram, transmural action potentials from epicardium (Epi) and endocardium (Endo), transmural repolarization dispersion (TDR) were recorded, and the incidences of triggered activity and ventricular arrhythmias were obtained at rapid cycle lengths. The results showed that TDR and the serum MDA and NT-proBNP levels were increased, and LVEF and the serum SOD level decreased in the adriamycin group compared with the control group. The incidences of triggered activity and ventricular arrhythmia were significantly higher in the adriamycin group than those in the control group (P<0.05). In the carvedilol group as compared with the adriamycin group, the serum SOD level and the LVEF were substantially increased; the TDR, and the serum MDA and NT-proBNP levels were significantly decreased; the incidences of triggered activity and ventricular arrhythmia were obviously reduced (P<0.05). There were no significant differences in the levels of MDA and SOD, LVEF, TDR and the incidences of triggered activity and ventricular arrhythmia between the adriamycin group and the metoprolol group. It was concluded that carvedilol may inhibit triggered activity and ventricular arrhythmias in rabbit with adriamycin-induced cardiomyopathy, which is related to the decrease in oxygen free radials.
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http://dx.doi.org/10.1007/s11596-012-0058-yDOI Listing
June 2012

Carvedilol and its new analogs suppress arrhythmogenic store overload-induced Ca2+ release.

Nat Med 2011 Jul 10;17(8):1003-9. Epub 2011 Jul 10.

Libin Cardiovascular Institute of Alberta, Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.

Carvedilol is one of the most effective beta blockers for preventing ventricular tachyarrhythmias in heart failure, but the mechanisms underlying its favorable antiarrhythmic benefits remain unclear. Spontaneous Ca(2+) waves, also called store overload-induced Ca(2+) release (SOICR), evoke ventricular tachyarrhythmias in individuals with heart failure. Here we show that carvedilol is the only beta blocker tested that effectively suppresses SOICR by directly reducing the open duration of the cardiac ryanodine receptor (RyR2). This unique anti-SOICR activity of carvedilol, combined with its beta-blocking activity, probably contributes to its favorable antiarrhythmic effect. To enable optimal titration of carvedilol's actions as a beta blocker and as a suppressor of SOICR separately, we developed a new SOICR-inhibiting, minimally beta-blocking carvedilol analog, VK-II-86. VK-II-86 prevented stress-induced ventricular tachyarrhythmias in RyR2-mutant mice and did so more effectively when combined with either of the selective beta blockers metoprolol or bisoprolol. Combining SOICR inhibition with optimal beta blockade has the potential to provide antiarrhythmic therapy that can be tailored to individual patients.
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http://dx.doi.org/10.1038/nm.2406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268079PMC
July 2011

Effects of hydrocortisone sodium succinate on voltage-gated sodium current in trigeminal ganglion neurons of rat.

Neurol Res 2011 Apr;33(3):295-9

Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objective: The effects of hydrocortisone sodium succinate on voltage-gated sodium current (I(Na)) were investigated by using the patch-clamp technique in trigeminal ganglion (TG) neurons of rat.

Methods: I(Na) was recorded by whole-cell patch-clamp techniques after different concentrations of hydrocortisone sodium succinate were perfused in TG neurons of rat.

Results: The results showed that hydrocortisone sodium succinate could inhibit I(Na) in concentration-dependent manner. Hydrocortisone sodium succinate 0.1, 0.3, 1, 3 μmol/l reduced I(Na) by 19.4±4.3, 26.7±3.9, 38.1±6.1, 69.6±5.4% respectively. The IC(50) was 1.58 μmol/l. This inhibitory effect occurred quickly (within 1 minute). However, hydrocortisone sodium succinate had no significant effect on the activation and inactivation courses of I(Na).

Conclusion: It is suggested that the rapid inhibition of I(Na) in TG neurons by hydrocortisone sodium succinate is probably related to non-genomic effect. This inhibition might participate in the relaxation of pain in some emergency states.
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http://dx.doi.org/10.1179/016164110X12714125204515DOI Listing
April 2011

Reduced threshold for luminal Ca2+ activation of RyR1 underlies a causal mechanism of porcine malignant hyperthermia.

J Biol Chem 2008 Jul 27;283(30):20813-20. Epub 2008 May 27.

Libin Cardiovascular Institutes of Alberta, Department of Physiology, University of Calgary, Calgary, Alberta, Canada.

Naturally occurring mutations in the skeletal muscle Ca(2+) release channel/ryanodine receptor RyR1 are linked to malignant hyperthermia (MH), a life-threatening complication of general anesthesia. Although it has long been recognized that MH results from uncontrolled or spontaneous Ca(2+) release from the sarcoplasmic reticulum, how MH RyR1 mutations render the sarcoplasmic reticulum susceptible to volatile anesthetic-induced spontaneous Ca(2+) release is unclear. Here we investigated the impact of the porcine MH mutation, R615C, the human equivalent of which also causes MH, on the intrinsic properties of the RyR1 channel and the propensity for spontaneous Ca(2+) release during store Ca(2+) overload, a process we refer to as store overload-induced Ca(2+) release (SOICR). Single channel analyses revealed that the R615C mutation markedly enhanced the luminal Ca(2+) activation of RyR1. Moreover, HEK293 cells expressing the R615C mutant displayed a reduced threshold for SOICR compared with cells expressing wild type RyR1. Furthermore, the MH-triggering agent, halothane, potentiated the response of RyR1 to luminal Ca(2+) and SOICR. Conversely, dantrolene, an effective treatment for MH, suppressed SOICR in HEK293 cells expressing the R615C mutant, but not in cells expressing an RyR2 mutant. These data suggest that the R615C mutation confers MH susceptibility by reducing the threshold for luminal Ca(2+) activation and SOICR, whereas volatile anesthetics trigger MH by further reducing the threshold, and dantrolene suppresses MH by increasing the SOICR threshold. Together, our data support a view in which altered luminal Ca(2+) regulation of RyR1 represents a primary causal mechanism of MH.
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http://dx.doi.org/10.1074/jbc.M801944200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2475718PMC
July 2008

Removal of FKBP12.6 does not alter the conductance and activation of the cardiac ryanodine receptor or the susceptibility to stress-induced ventricular arrhythmias.

J Biol Chem 2007 Nov 5;282(48):34828-38. Epub 2007 Oct 5.

Libin Cardiovascular Institute of Alberta, Department of Physiology and Biophysics, University of Calgary, Calgary, AB, T2N 4N1, Canada.

The 12.6-kDa FK506-binding protein (FKBP12.6) is considered to be a key regulator of the cardiac ryanodine receptor (RyR2), but its precise role in RyR2 function is complex and controversial. In the present study we investigated the impact of FKBP12.6 removal on the properties of the RyR2 channel and the propensity for spontaneous Ca(2+) release and the occurrence of ventricular arrhythmias. Single channel recordings in lipid bilayers showed that FK506 treatment of recombinant RyR2 co-expressed with or without FKBP12.6 or native canine RyR2 did not induce long-lived subconductance states. [(3)H]Ryanodine binding studies revealed that coexpression with or without FKBP12.6 or treatment with or without FK506 did not alter the sensitivity of RyR2 to activation by Ca(2+) or caffeine. Furthermore, single cell Ca(2+) imaging analyses demonstrated that HEK293 cells co-expressing RyR2 and FKBP12.6 or expressing RyR2 alone displayed the same propensity for spontaneous Ca(2+) release or store overload-induced Ca(2+) release (SOICR). FK506 increased the amplitude and decreased the frequency of SOICR in HEK293 cells expressing RyR2 with or without FKBP12.6, indicating that the action of FK506 on SOICR is independent of FKBP12.6. As with recombinant RyR2, the conductance and ligand-gating properties of single RyR2 channels from FKBP12.6-null mice were indistinguishable from those of single wild type channels. Moreover, FKBP12.6-null mice did not exhibit enhanced susceptibility to stress-induced ventricular arrhythmias, in contrast to previous reports. Collectively, our results demonstrate that the loss of FKBP12.6 has no significant effect on the conduction and activation of RyR2 or the propensity for spontaneous Ca(2+) release and stress-induced ventricular arrhythmias.
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http://dx.doi.org/10.1074/jbc.M707423200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2760432PMC
November 2007

Effects of volsartan on transmural heterogeneous changes of transient outward potassium currents in hypertrophic cardiomyocytes in rabbits.

J Huazhong Univ Sci Technolog Med Sci 2004 ;24(5):437-40

Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

The transmural heterogeneous changes of transient outward potassium currents (Ito) in rabbit hypertrophic cardiaomyocytes and the effects of long-term prophylactic treatment with volsartan were investigated. Rabbits were divided into hypertrophy group (left ventricular hypertrophy induced by partial ligation of abdominal aorta), vol-treated group (volsartan was administrated after the ligation), and control group (sham operated). Myocytes were isolated by a two-step enzymatical method. The sub-endocardial (Endo) and sub-epicardium (Epi) tissues were separated from midmyocardium (Mid) with a razor. Whole-cell patch-clamp technique was used to record potassium currents. The results showed that membrane capacitance was larger in hypertrophic cells than those in control and vol-treated cells (P<0.01 vs control cells, n=30). The densities of Ito in hypertrophic cells were reduced by sub-epicardium (Epi) (27.8 +/- 2.9) %, midmyocardium (Mid) (41.0+/-4.7) %, and sub-endocardium (Endo) (20.3 +/- 3.4) % compared with those in control cells. The decrease of Ito density was more pronounced in Mid than in Epi and Endo (P<0.01 vs Epi or Endo). There were no significant differences in Ito densities between vol-treated group and control group in three layers separately. In conclusion, volsartan can inhibit the transmural heterogeneous changes of Ito in left ventricular hypertrophic cardiomyocytes in rabbit.
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http://dx.doi.org/10.1007/BF02831102DOI Listing
May 2006

Long-term effects of imidapril on calcium and potassium currents in rabbit left ventricular hypertrophic myocytes.

Chin Med J (Engl) 2003 Dec;116(12):1795-8

Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Objective: To investigate the long-term effects of imidapril (IMI) on action potential and calcium and potassium currents in rabbit left ventricular hypertrophic myocytes.

Methods: Rabbits were randomly divided into three groups: IMI-treated, hypertrophic and sham-operated control groups. Cardiac hypertrophy was induced in hypertrophy group by partial ligation of the abdominal aorta. In the IMI-treated group, the rabbits were administered IMI (1.5 mg x kg(-1) x d(-1)) for 8 weeks after surgery. In the sham-operated control group, the animals underwent an abdominal laparotomy without further procedure. Whole-cell patch clamp technique was used to record ionic currents.

Results: Membrane capacitance was larger in hypertrophic cells than in sham-operated cells or IMI-treated cells. Action potential duration was lengthened in hypertrophic cells and was remarkably shortened by IMI. The density of ICa, L was reduced from 12.8 +/- 0.7 pA/pF in the sham-operated cells, to 7.7 +/- 0.8 pA/pF in hypertrophic cells, while it resembled the control cells after IMI treatment (11.9 +/- 1.0 pA/pF). After IMI treatment, the density of I(Ks,tail) was enhanced from 2.5 +/- 0.1 pA/pF in hypertrophic cells to 4.7 +/- 0.6 pA/pF (n = 7, P < 0.01), which was similar to the sham-operated cells. The densities of Ito and IK1 were significantly increased in IMI-treated cells, from 3.8 +/- 0.4 pA/pF and 3.7 +/- 0.5 pA/pF in the hypertrophic cells to 6.4 +/- 0.8 pA/pF and 6.5 +/- 0.3 pA/pF, respectively, but the IKr densities were not different in the three groups.

Conclusion: IMI could reverse the increase in membrane capacitance in hypertrophic cells, shorten action potential duration, and increase the densities of ICa, L, IKs, Ito and IK1 in hypertrophic cells.
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December 2003