Publications by authors named "Caimei Zhang"

12 Publications

  • Page 1 of 1

Evaluation of the relationship among dental fear, scaling and root planing and periodontal status using periodontitis stages: A retrospective study.

J Dent Sci 2022 Jan 21;17(1):293-299. Epub 2021 Apr 21.

Department of Periodontology, Stomatological Hospital, Southern Medical University, Guangzhou, China.

Background/purpose: Patients with periodontal disease have higher dental fear levels, which may have negative effects on their clinical outcome during scaling and root planing (SRP). The present study used the new classification of periodontitis and validated questionnaires to assess the relationship among dental fear, SRP pain and periodontal status.

Materials And Methods: A total of 120 periodontitis patients were enrolled and staging according to the new classification of periodontitis. SRP was performed, and the visual analog scale (VAS) to assess pain was used with every patient after treatment. Questionnaires, including Corah's Dental Anxiety Scale (DAS), Dental Fear Survey (DFS), and short-form Dental Anxiety Inventory (S-DAI) were implemented from the first attendance and subsequent visits after 6 months. The patients were grouped by DAS scores. The statistical analysis was performed using T-test, chi-square, Pearson and Spearman correlative analysis.

Results: Compared to pre-SRP treatment, the dental fear level on DFS was decreased in the posttreatment period for all periodontitis stages. There were no statistically significant differences in S-DAI and DAS between pretreatment and posttreatment periods in stage I and II; meanwhile, there were statistically differences in stage III and IV. The correlation among periodontitis stages, VAS and dental fear level was significant. The proportion of high periodontitis stages was increased in high dental fear group.

Conclusion: SRP can reduce dental fear levels in all periodontitis stages, especially in stage III and IV. Correlations exist among periodontal status, dental fear and SRP pain. High dental fear is associated with poor periodontal status.
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http://dx.doi.org/10.1016/j.jds.2021.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8739248PMC
January 2022

α-Catenin-dependent cytoskeletal tension controls Yap activity in the heart.

Development 2018 03 8;145(5). Epub 2018 Mar 8.

Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA

Shortly after birth, muscle cells of the mammalian heart lose their ability to divide. At the same time, the N-cadherin/catenin cell adhesion complex accumulates at the cell termini, creating a specialized type of cell-cell contact called the intercalated disc (ICD). To investigate the relationship between ICD maturation and proliferation, αE-catenin () and αT-catenin () genes were deleted to generate cardiac-specific α-catenin double knockout (DKO) mice. DKO mice exhibited aberrant N-cadherin expression, mislocalized actomyosin activity and increased cardiomyocyte proliferation that was dependent on Yap activity. To assess effects on tension, cardiomyocytes were cultured on deformable polyacrylamide hydrogels of varying stiffness. When grown on a stiff substrate, DKO cardiomyocytes exhibited increased cell spreading, nuclear Yap and proliferation. A low dose of either a myosin or RhoA inhibitor was sufficient to block Yap accumulation in the nucleus. Finally, activation of RhoA was sufficient to increase nuclear Yap in wild-type cardiomyocytes. These data demonstrate that α-catenins regulate ICD maturation and actomyosin contractility, which, in turn, control Yap subcellular localization, thus providing an explanation for the loss of proliferative capacity in the newborn mammalian heart.
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http://dx.doi.org/10.1242/dev.149823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868989PMC
March 2018

MG53 is dispensable for T-tubule maturation but critical for maintaining T-tubule integrity following cardiac stress.

J Mol Cell Cardiol 2017 11 16;112:123-130. Epub 2017 Aug 16.

Division of Cardiovascular Medicine, Department of Internal Medicine, Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Department of Veterans Affairs Medical Center, Iowa City, IA 52242, USA. Electronic address:

The cardiac transverse (T)-tubule membrane system is the safeguard for cardiac function and undergoes dramatic remodeling in response to cardiac stress. However, the mechanism by which cardiomyocytes repair damaged T-tubule network remains unclear. In the present study, we tested the hypothesis that MG53, a muscle-specific membrane repair protein, antagonizes T-tubule damage to protect against maladaptive remodeling and thereby loss of excitation-contraction coupling and cardiac function. Using MG53-knockout (MG53-KO) mice, we first established that deficiency of MG53 had no impact on maturation of the T-tubule network in developing hearts. Additionally, MG53 ablation did not influence T-tubule integrity in unstressed adult hearts as late as 10months of age. Following left ventricular pressure overload-induced cardiac stress, MG53 protein levels were increased by approximately three-fold in wild-type mice, indicating that pathological stress induces a significant upregulation of MG53. MG53-deficient mice had worsened T-tubule disruption and pronounced dysregulation of Ca handling properties, including decreased Ca transient amplitude and prolonged time to peak and decay. Moreover, MG53 deficiency exacerbated cardiac hypertrophy and dysfunction and decreased survival following cardiac stress. Our data suggest MG53 is not required for T-tubule development and maintenance in normal physiology. However, MG53 is essential to preserve T-tubule integrity and thereby Ca handling properties and cardiac function under pathological cardiac stress.
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http://dx.doi.org/10.1016/j.yjmcc.2017.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682927PMC
November 2017

Berbamine postconditioning protects the heart from ischemia/reperfusion injury through modulation of autophagy.

Cell Death Dis 2017 02 2;8(2):e2577. Epub 2017 Feb 2.

Key Laboratory of Stem Cell Biology and Laboratory of Molecular Cardiology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine & Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Pretreatment of berbamine protects the heart from ischemia/reperfusion (I/R) injury. However it is unknown whether it has cardioprotection when given at the onset of reperfusion (postconditioning (PoC)), a protocol with more clinical impact. Autophagy is upregulated in I/R myocardium and exacerbates cardiomyocyte death during reperfusion. However, it is unknown whether the autophagy during reperfusion is regulated by berbamine. Here we investigated whether berbamine PoC (BMPoC) protects the heart through regulation of autophagy by analyzing the effects of BMPoC on infarct size and/or cell death, functional recovery and autophagy in perfused rat hearts and isolated cardiomyocytes subjected to I/R. Berbamine from 10 to 100 nM given during the first 5 min of reperfusion concentration-dependently improved post-ischemic myocardial function and attenuated cell death. Similar protections were observed in cardiomyocytes subjected to simulated I/R. Meanwhile, BMPoC prevented I/R-induced impairment of autophagosome processing in cardiomyocytes, characterized by increased LC3-II level and GFP-LC3 puncta, and decreased p62 degradation. Besides, lysosomal inhibitor chloroquine did not induce additional increase of LC3-II and P62 abundance after I/R but it reversed the effects of BMPoC in those parameters in cardiomyocytes, suggesting that I/R-impaired autophagic flux is restored by BMPoC. Moreover, I/R injury was accompanied by enhanced expression of Beclin 1, which was significantly inhibited by BMPoC. In vitro and in vivo adenovirus-mediated knockdown of Beclin 1 in myocardium and cardiomyocytes restored I/R-impaired autophagosome processing, associated with an improvement of post-ischemic recovery of myocardial contractile function and a reduction of cell death, but it did not have additive effects to BMPoC. Conversely, overexpression of Beclin 1 abolished the cardioprotection of BMPoC as did by overexpression of an essential autophagy gene Atg5. Furthermore, BMPoC-mediated cardioprotection was abolished by a specific Akt1/2 inhibitor A6730. Our results demonstrate that BMPoC confers cardioprotection by modulating autophagy during reperfusion through the activation of PI3K/Akt signaling pathway.
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http://dx.doi.org/10.1038/cddis.2017.7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386498PMC
February 2017

Cholesterol is required for maintaining T-tubule integrity and intercellular connections at intercalated discs in cardiomyocytes.

J Mol Cell Cardiol 2016 08 30;97:204-12. Epub 2016 May 30.

Division of Cardiovascular Medicine, Department of Internal Medicine, François M. Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Department of Veterans Affairs Medical Center, Iowa City, IA 52242, USA. Electronic address:

Backgrounds: Low serum cholesterol levels are associated with cardiac arrhythmias and poor prognosis in patients with chronic heart failure. However, the underlying mechanisms by which decreases in cholesterol content lead to cardiac dysfunction remain unclear. Multiple studies have implicated damage to cardiac transverse (T)-tubules as a key mediator of excitation-contraction (E-C) coupling dysfunction and heart failure. Since the T-tubule membrane system is enriched in cholesterol, we hypothesized that depletion of membrane cholesterol promotes T-tubule remodeling and E-C coupling dysfunction.

Methods And Results: We first examined the impact of membrane cholesterol depletion on T-tubule architecture by treating isolated C57BL/6 murine cardiomyocytes with methyl-β-cyclodextrin (MβCD). T-tubule structural integrity was progressively decreased by MβCD in a concentration- and time-dependent manner. Membrane cholesterol depletion also promoted a severe decrease in the amplitude of Ca(2+) transients and an increase in Ca(2+) release dyssynchrony as well as a significant increase in the frequency of spontaneous Ca(2+) sparks. Reintroduction of cholesterol restored T-tubule integrity and partially restored Ca(2+) handling properties in acutely-treated myocytes and slowed T-tubule deterioration in response to chronic MβCD exposure. Studies were extended to determine the impact of membrane cholesterol depletion on T-tubule structure in intact hearts. In addition to T-tubule remodeling, Langendorff perfusion of MβCD resulted in rapid and severe disruption of the intercellular connections between cardiomyocytes, in particular at intercalated disc regions in intact hearts.

Conclusions: These data provide the first evidence that cholesterol plays a critical role in maintaining cardiac T-tubule structure as well as the integrity of intercalated discs.
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http://dx.doi.org/10.1016/j.yjmcc.2016.05.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002380PMC
August 2016

Molecular Determinants of Calpain-dependent Cleavage of Junctophilin-2 Protein in Cardiomyocytes.

J Biol Chem 2015 Jul 10;290(29):17946-17955. Epub 2015 Jun 10.

Division of Cardiovascular Medicine, Department of Internal Medicine and François M. Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242. Electronic address:

Junctophilin-2 (JP2), a membrane-binding protein that provides a structural bridge between the plasmalemma and sarcoplasmic reticulum, is essential for precise Ca(2+)-induced Ca(2+) release during excitation-contraction coupling in cardiomyocytes. In animal and human failing hearts, expression of JP2 is decreased markedly, but the molecular mechanisms underlying JP2 down-regulation remain incompletely defined. In mouse hearts, ischemia/reperfusion injury resulted in acute JP2 down-regulation, which was attenuated by pretreatment with the calpain inhibitor MDL-28170 or by transgenic overexpression of calpastatin, an endogenous calpain inhibitor. Using a combination of computational analysis to predict calpain cleavage sites and in vitro calpain proteolysis reactions, we identified four putative calpain cleavage sites within JP2 with three N-terminal and one C-terminal cleavage sites. Mutagenesis defined the C-terminal region of JP2 as the predominant calpain cleavage site. Exogenous expression of putative JP2 cleavage fragments was not sufficient to rescue Ca(2+) handling in JP2-deficient cardiomyocytes, indicating that cleaved JP2 is non-functional for normal Ca(2+)-induced Ca(2+) release. These data provide new molecular insights into the posttranslational regulatory mechanisms of JP2 in cardiac diseases.
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http://dx.doi.org/10.1074/jbc.M115.652396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505042PMC
July 2015

In situ single photon confocal imaging of cardiomyocyte T-tubule system from Langendorff-perfused hearts.

Front Physiol 2015 6;6:134. Epub 2015 May 6.

Division of Cardiovascular Medicine, Department of Internal Medicine, Francois M. Abboud Cardiovascular Research Center, Carver College of Medicine, University of Iowa Iowa City, IA, USA.

Transverse tubules (T-tubules) are orderly invaginations of the sarcolemma in mammalian cardiomyocytes. The integrity of T-tubule architecture is critical for cardiac excitation-contraction coupling function. T-tubule remodeling is recognized as a key player in cardiac dysfunction. Early studies on T-tubule structure were based on electron microscopy, which uncovered important information about the T-tubule architecture. The advent of fluorescent membrane probes allowed the application of confocal microscopy to investigations of T-tubule structure. Studies have now been extended beyond single cardiomyocytes to examine the T-tubule network in intact hearts through in situ confocal imaging of Langendorff-perfused hearts. This technique has allowed visualization of T-tubule organization in their natural habitat, avoiding the damage induced by isolation of cardiomyocytes. Additionally, it is possible to obtain T-tubule images in different subepicardial regions in a single intact heart. We review how this state-of-the-art imaging technique has provided important mechanistic insights into maturation of T-tubules in developing hearts and defined the role of T-tubule remodeling in development and progression of heart failure.
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http://dx.doi.org/10.3389/fphys.2015.00134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422017PMC
May 2015

Repression of the Central Splicing Regulator RBFox2 Is Functionally Linked to Pressure Overload-Induced Heart Failure.

Cell Rep 2015 Mar 5;10(9):1521-1533. Epub 2015 Mar 5.

Department of Cellular and Molecular Medicine University of California, San Diego, La Jolla, CA 92093-0651, USA; Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093-0651, USA. Electronic address:

Heart failure is characterized by the transition from an initial compensatory response to decompensation, which can be partially mimicked by transverse aortic constriction (TAC) in rodent models. Numerous signaling molecules have been shown to be part of the compensatory program, but relatively little is known about the transition to decompensation that leads to heart failure. Here, we show that TAC potently decreases the RBFox2 protein in the mouse heart, and cardiac ablation of this critical splicing regulator generates many phenotypes resembling those associated with decompensation in the failing heart. Global analysis reveals that RBFox2 regulates splicing of many genes implicated in heart function and disease. A subset of these genes undergoes developmental regulation during postnatal heart remodeling, which is reversed in TAC-treated and RBFox2 knockout mice. These findings suggest that RBFox2 may be a critical stress sensor during pressure overload-induced heart failure.
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http://dx.doi.org/10.1016/j.celrep.2015.02.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559494PMC
March 2015

Overexpression of junctophilin-2 does not enhance baseline function but attenuates heart failure development after cardiac stress.

Proc Natl Acad Sci U S A 2014 Aug 4;111(33):12240-5. Epub 2014 Aug 4.

Division of Cardiovascular Medicine, Department of Internal Medicine, and Francois M. Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242;

Heart failure is accompanied by a loss of the orderly disposition of transverse (T)-tubules and a decrease of their associations with the junctional sarcoplasmic reticulum (jSR). Junctophilin-2 (JP2) is a structural protein responsible for jSR/T-tubule docking. Animal models of cardiac stresses demonstrate that down-regulation of JP2 contributes to T-tubule disorganization, loss of excitation-contraction coupling, and heart failure development. Our objective was to determine whether JP2 overexpression attenuates stress-induced T-tubule disorganization and protects against heart failure progression. We therefore generated transgenic mice with cardiac-specific JP2 overexpression (JP2-OE). Baseline cardiac function and Ca(2+) handling properties were similar between JP2-OE and control mice. However, JP2-OE mice displayed a significant increase in the junctional coupling area between T-tubules and the SR and an elevated expression of the Na(+)/Ca(2+) exchanger, although other excitation-contraction coupling protein levels were not significantly changed. Despite similar cardiac function at baseline, overexpression of JP2 provided significantly protective benefits after pressure overload. This was accompanied by a decreased percentage of surviving mice that developed heart failure, as well as preservation of T-tubule network integrity in both the left and right ventricles. Taken together, these data suggest that strategies to maintain JP2 levels can prevent the progression from hypertrophy to heart failure.
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http://dx.doi.org/10.1073/pnas.1412729111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143026PMC
August 2014

Microtubule-mediated defects in junctophilin-2 trafficking contribute to myocyte transverse-tubule remodeling and Ca2+ handling dysfunction in heart failure.

Circulation 2014 Apr 11;129(17):1742-50. Epub 2014 Feb 11.

Division of Cardiovascular Medicine, Department of Internal Medicine (C.Z., B.C., A.G., Y.Z., S.G., W.K., R.M.W., F.L.J., M.E.A., L.-S.S.) and Department of Molecular Physiology and Biophysics (M.E.A.), University of Iowa Carver College of Medicine, Iowa City, IA; Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China (Y.Z., J.H.); Division of Cardiovascular Surgery, Mayo Clinic, Rochester, MN (J.D.M.); Department of Pharmacology, College of Basic Medicine, Anhui Medical University, Hefei, China (S.G.); Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA (C.Y., L.F.S.); Department of Veterans Affairs Medical Center, Iowa City, IA (K.Z.); and Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX (X.H.T.W.).

Background: Cardiac dysfunction in failing hearts of human patients and animal models is associated with both microtubule densification and transverse-tubule (T-tubule) remodeling. Our objective was to investigate whether microtubule densification contributes to T-tubule remodeling and excitation-contraction coupling dysfunction in heart disease.

Methods And Results: In a mouse model of pressure overload-induced cardiomyopathy by transaortic banding, colchicine, a microtubule depolymerizer, significantly ameliorated T-tubule remodeling and cardiac dysfunction. In cultured cardiomyocytes, microtubule depolymerization with nocodazole or colchicine profoundly attenuated T-tubule impairment, whereas microtubule polymerization/stabilization with taxol accelerated T-tubule remodeling. In situ immunofluorescence of heart tissue sections demonstrated significant disorganization of junctophilin-2 (JP2), a protein that bridges the T-tubule and sarcoplasmic reticulum membranes, in transaortic banded hearts as well as in human failing hearts, whereas colchicine injection significantly preserved the distribution of JP2 in transaortic banded hearts. In isolated mouse cardiomyocytes, prolonged culture or treatment with taxol resulted in pronounced redistribution of JP2 from T-tubules to the peripheral plasma membrane, without changing total JP2 expression. Nocodazole treatment antagonized JP2 redistribution. Moreover, overexpression of a dominant-negative mutant of kinesin 1, a microtubule motor protein responsible for anterograde trafficking of proteins, protected against JP2 redistribution and T-tubule remodeling in culture. Finally, nocodazole treatment improved Ca(2+) handling in cultured myocytes by increasing the amplitude of Ca(2+) transients and reducing the frequency of Ca(2+) sparks.

Conclusion: Our data identify a mechanistic link between microtubule densification and T-tubule remodeling and reveal microtubule-mediated JP2 redistribution as a novel mechanism for T-tubule disruption, loss of excitation-contraction coupling, and heart failure.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.113.008452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006305PMC
April 2014

Critical roles of junctophilin-2 in T-tubule and excitation-contraction coupling maturation during postnatal development.

Cardiovasc Res 2013 Oct 16;100(1):54-62. Epub 2013 Jul 16.

Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver, College of Medicine, Iowa City, IA 52242, USA.

Aims: Emerging evidence indicates a critical role for junctophilin-2 (JP2) in T-tubule integrity and assembly of cardiac dyads in adult ventricular myocytes. In the postnatal stage, one of the critical features of myocyte maturation is development of the T-tubule system, though the mechanisms remain poorly understood. In this study, we aim to determine whether JP2 is required for normal cardiac T-tubule maturation.

Methods And Results: Using in situ confocal imaging of intact murine hearts, we found T-tubules were absent in both left- and right-ventricular myocytes at postnatal Day 8 and did not appear until Day 10. Quantification of T-tubule structural integrity using the T-tubule power (TT(power)) index revealed a progressive increase in TT(power) between postnatal Days 10 and 19. By postnatal Day 19, TT(power) was similar to that in adult murine cardiomyocytes, indicative of a nearly matured T-tubule network. JP2 levels increased dramatically during development, reaching levels observed in adult hearts by postnatal Day 14. Deficiency of JP2, using a mouse model in which a JP2-specific shRNA is expressed during embryonic development, severely impaired T-tubule maturation, with equivalent decreases in the left- and right-ventricular TT(power). We also detected a gradual increase in the density of transverse but not longitudinal tubules during development, and JP2 deficiency abolished the increase in the density of transverse elements. Alterations in T-tubules caused significant reduction in Ca(2+) transient amplitude and marked increase in Ca(2+) release dyssynchrony, Ca(2+) alternans, and spontaneous Ca(2+) waves, leading to contractile failure.

Conclusion: Our data identify a critical role for JP2 in T-tubule and excitation-contraction coupling maturation during development.
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http://dx.doi.org/10.1093/cvr/cvt180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778961PMC
October 2013

Emerging mechanisms of T-tubule remodelling in heart failure.

Cardiovasc Res 2013 May 7;98(2):204-15. Epub 2013 Feb 7.

Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

Cardiac excitation-contraction coupling occurs primarily at the sites of transverse (T)-tubule/sarcoplasmic reticulum junctions. The orderly T-tubule network guarantees the instantaneous excitation and synchronous activation of nearly all Ca(2+) release sites throughout the large ventricular myocyte. Because of the critical roles played by T-tubules and the array of channels and transporters localized to the T-tubule membrane network, T-tubule architecture has recently become an area of considerable research interest in the cardiovascular field. This review will focus on the current knowledge regarding normal T-tubule structure and function in the heart, T-tubule remodelling in the transition from compensated hypertrophy to heart failure, and the impact of T-tubule remodelling on myocyte Ca(2+) handling function. In the last section, we discuss the molecular mechanisms underlying T-tubule remodelling in heart disease.
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http://dx.doi.org/10.1093/cvr/cvt020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3697065PMC
May 2013
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