Publications by authors named "Yongnan Lyu"

10 Publications

  • Page 1 of 1

Elevated Plasma Angiopoietinlike Protein 5 (ANGPTL5) Is More Positively Associated with Glucose Metabolism Disorders in Patients with Metabolic Syndrome.

Med Sci Monit 2021 Jan 24;27:e929626. Epub 2021 Jan 24.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (mainland).

BACKGROUND Angiopoietinlike protein 5 (ANGPTL5) is an adipocytokine and has an important role in metabolic processes including lipid metabolism, obesity, and type 2 diabetes mellitus. On the basis of these roles, the present study aimed to investigate the level and role of plasma ANGPTL5 in metabolic syndrome (MS) patients. MATERIAL AND METHODS A total of 139 participants was enrolled in this study; 69 of them were diagnosed with MS. Plasma ANGPTL5 levels were measured by enzyme-linked immunosorbent assay. Sex, age, and other laboratory tests were compared statistically. Correlations between ANGPTL5 and biochemical parameters such as lipid levels and insulin resistance were all evaluated statistically. RESULTS In patients with MS, plasma ANGPTL5 levels were higher than in those without MS (P<0.05). Moreover, after adjusting for the glucose profiles, positive correlations were found between plasma ANGPTL5 levels and body mass index (BMI), waist circumference, and waist-hip ratio (WHR); a weak negative correlation was found between ANGPTL5 concentration and high-density lipoprotein cholesterol. After controlling the lipid profiles, positive correlations were found between ANGPTL5 concentration and BMI, WHR, fasting plasma glucose, fasting insulin, glycated hemoglobin, and homeostatic model assessment (HOMA) of insulin resistance; a negative correlation was found between plasma ANGPTL5 concentration and HOMA of ß-cell function. The area under the curve was approximately 0.912 in receiver operating characteristic curve analysis. CONCLUSIONS The findings in the present study showed that plasma ANGPTL5 was more positively correlated with glucose metabolism disorders than with lipid metabolism disorders in patients with MS, which suggested that ANGPTL5 might serve as a potential and useful clinical predictor of MS.
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http://dx.doi.org/10.12659/MSM.929626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841967PMC
January 2021

GDF15 as a biomarker of ageing.

Exp Gerontol 2021 Apr 6;146:111228. Epub 2021 Jan 6.

Department of Clinical Laboratory, Wuhan University, Renmin Hospital, Wuhan 430060, Hubei Province, China. Electronic address:

The ageing process is accompanied by the gradual development of chronic systemic inflammation (inflamm-ageing). Growth differentiation factor 15 (GDF15) is associated with inflammation and known to be a stress-induced factor. The present study aimed to explore the association of GDF15 with ageing. In this cross-sectional study, serum GDF15, hematological parameters, and biomedical parameters were determined in 120 healthy individuals (23-83 years old, males). Three telomere related parameters, including telomere length, telomerase activity, and the expression of human telomerase reverse transcriptase (hTERT) mRNA were also quantified. Our results showed that the older group has a higher levels of GDF15 and lower expression of hTERT mRNA, and PBMC telomerase activity (p < 0.001). In individuals with high GDF15 levels, they were older, and presented with the lower level of hTERT mRNA and T/S ratio (p < 0.01). Spearman correlation analysis shows that GDF15 positively correlated with age (r = 0.664, p < 0.001), and negatively correlated with telomere length (r = -0.434, p < 0.001), telomerase activity (r = -0.231, p = 0.012), and hTERT mRNA (r = -0.206, p = 0.024). Furthermore, in multivariate regression analysis, GDF15 levels showed a statistically significant linear and negative relationship with PBMC telomerase activity (β-coefficient = -0.583, 95% CI -1.044 to -0.122, p = 0.014), telomere length (β-coefficient = -0.200, 95% CI -0.305 to -0.094, p < 0.001), and hTERT mRNA (β-coefficient = -0.207, 95% CI -0.312 to -0.102, p < 0.001) after adjusting for confounders. These results support that circulating GDF15 is the potential biomarker of ageing that may influence the risk and progression of multiple ageing conditions.
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http://dx.doi.org/10.1016/j.exger.2021.111228DOI Listing
April 2021

Potential associations of circulating growth differentiation factor-15 with sex hormones in male patients with coronary artery disease.

Biomed Pharmacother 2019 Jun 22;114:108792. Epub 2019 Mar 22.

Dept of Clinical Laboratory, Wuhan Univ, Renmin Hospital, Wuhan 430060, Hubei Province, PR China. Electronic address:

This study aimed to explore the association between growth differentiation factor-15 (GDF-15), a stress-induced factor, and sex hormones in male patients with coronary artery disease (CAD). In this study, we recruited 253 male patients with CAD and 205 male controls. Patients were divided into three groups in accordance with GDF-15 tertiles. Serum levels of GDF-15, testosterone, estradiol and other biochemical variables were measured. Serum levels of GDF-15 were significantly increased and serum testosterone and testosterone/estradiol ratio (T/E2 ratio) were significantly decreased in CAD patients compared with controls. Patients with high GDF-15 levels had lower testosterone (203.97, 95% CI 154.67-328.30 vs. 303.98, 95% CI 246.93-345.66; P = 0.001) and T/E2 ratio (8.82, 95% CI 5.77-11.41 vs. 11.07, 95% CI 7.91-14.32; P = 0.013). Correlation analyses showed that serum GDF-15 levels inversely correlated with testosterone levels (r = -0.339) and T/E2 ratio (r = -0.365) (both P < 0.001). In multivariate regression analyses, the association between GDF-15 and T/E2 ratio was maintained (B=-0.442, 95% CI -99.568 to -6.991, P = 0.015). Furthermore, in vitro studies showed a synergistic effect of testosterone and estradiol on GDF-15 secretion, and demonstrated that testosterone association with estradiol decreased GDF-15 secretion through androgen receptor/estrogen receptor-mediated pathways. Together, these results suggest that upregulation of GDF-15 in the presence of low and imbalanced sex hormone levels may contribute to CAD. Thus, restoring the balance of testosterone and estradiol may inhibit the effects of GDF-15 and serve as a promising therapeutic strategy for the treatment of CAD.
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http://dx.doi.org/10.1016/j.biopha.2019.108792DOI Listing
June 2019

Potential relation between soluble growth differentiation factor-15 and testosterone deficiency in male patients with coronary artery disease.

Cardiovasc Diabetol 2019 02 28;18(1):21. Epub 2019 Feb 28.

Dept of Clinical Laboratory, Wuhan Univ, Renmin Hospital, Jiefang Road 238, Wuhan, 430060, Hubei, China.

Background: There is a mutual interaction between inflammation and endocrine disorders in the development of coronary artery disease (CAD). Growth differentiation factor-15 (GDF-15) is associated with CAD, and the effects of testosterone on CAD as reported in literature have been considered as anti-atherosclerotic. The present study aimed to examine the possible association between serum GDF-15 and testosterone in male CAD patients.

Methods: GDF-15 and testosterone concentrations were determined in blood samples of 426 male patients with CAD and 220 male controls. Serum concentrations of hs-CRP, and other baseline characteristics were also measured.

Results: Serum levels of GDF-15 were higher in CAD patients when compared to controls, and testosterone concentrations were lower (p < 0.001). Patients with low testosterone levels had higher concentrations of GDF-15 (p < 0.001). In stratified analyses, inverse relations between GDF-15 levels and testosterone were noted for almost all strata, stratified by categories of hs-CRP, leukocytes, neutrophils, neutrophil to lymphocyte ratio, glucose, HDL-c, and LDL-c, and whether had hypertension, diabetes, and underwent percutaneous coronary intervention (PCI). Furthermore, in the linear regression models with bootstrap resampling with 1000 replications, high GDF-15 levels were independently associated with testosterone deficiency in male patients with CAD.

Conclusions: In male patients with CAD, high GDF-15 levels were associated with testosterone deficiency. These results support that upregulation of GDF-15 in the presence of low testosterone levels during CAD progression is a potential mechanism by which GDF-15 affects CAD.
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http://dx.doi.org/10.1186/s12933-019-0823-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394066PMC
February 2019

Six-month evaluation of novel bioabsorbable scaffolds composed of poly-L-lactic acid and amorphous calcium phosphate nanoparticles in porcine coronary arteries.

J Biomater Appl 2018 08;33(2):227-233

1 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Objective Using coronary angiography and intravascular ultrasound methods to evaluate the performance of the novel fully bioabsorbable scaffold (NFBS) composed of poly-L-lactic acid/amorphous calcium phosphate (PLLA/ACP) at six-month follow-up by comparing with PLLA scaffolds Methods Twelve PLLA/ACP scaffolds and 12 PLLA scaffolds were implanted into the coronary arteries of 12 miniature pigs. Quantitative coronary angiography (QCA) was used to measure the reference vessel diameter (RVD), mean lumen diameter (MLD) and late lumen loss (LLL). According to IVUS images, we calculated the strut malapposition rate (SMR) at post implantation, strut overlap rate (SOR), reference vessel area (RVA), mean stent area (MSA), mean lumen area (MLA) and luminal patency rate (LPR) at six-month follow-up. The radial strength of the scaffold was evaluated using a catheter tensile testing machine. Results QCA results indicated that, at six month, MLD of PLLA/ACP scaffolds was greater than those of PLLA scaffolds (2.47 ± 0.22 mm vs. 2.08 ± 0.25 mm, P < 0.05); LLL of PLLA/ACP scaffolds was less than those of PLLA scaffolds (0.42 ± 0.20 mm vs. 0.75 ± 0.22 mm, P < 0.05). IVUS results showed the SMR and SOR were all significantly less with the PLLA/ACP scaffolds than the PLLA scaffolds (5.84% ± 3.56% vs. 17.72% ± 4.86%, P < 0.05) (6.17% ± 4.63% vs. 17.65% ± 4.29%, P < 0.05). MSA, MLA and LPR of the PLLA/ACP scaffolds were all greater than those of PLLA scaffolds (6.35 ± 0.45 mm vs. 5.35 ± 0.51 mm, P < 0.05) (4.76 ± 0.46 mm vs. 3.77 ± 0.46 mm, P < 0.05) (78.01% ± 12.29% vs. 61.69% ± 9.76%, P < 0.05). Radial strength of PLLA/ACP scaffold at six month was greater than that of PLLA scaffold (76.33 ± 3.14 N vs. 67.67 ± 3.63 N). Conclusion The NFBS had less stent recoil, better lumen patency rate and greater radial strength than PLLA scaffolds. The results suggest the NFBS scaffolds can maintain the structural strength and functional performance, which are effective for up to six months when implanted in porcine coronary arteries.
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http://dx.doi.org/10.1177/0885328218790332DOI Listing
August 2018

The pathogenic gene screening in a Chinese familial dilated cardiomyopathy pedigree from Hubei.

Gene 2018 Feb 3;642:159-162. Epub 2017 Nov 3.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China. Electronic address:

Dilated cardiomyopathy arises from mutations in many genes. TTN, the gene encoding the sarcomere protein titin, has been insufficiently analyzed for cardiomyopathy mutations because of its enormous size. In this study, we report a Chinese family with two members affected by TTN. Blood samples were collected from all family members. Genomic DNA was isolated from blood, and all coding exons and adjacent intronic sequences of the TTN gene were examined for mutation analysis using polymerase chain reaction (PCR)-based sequencing. The proband (III3) and his sister (III2) carry a TTN c.100126A>G (p.Thr33376Ala) missense mutation. The proband currently exhibits decreased cardiac function accompanied by malignant arrhythmia, and his sister has no obvious clinical symptoms and no abnormal ultrasound findings. The study found that there is a missense mutation in the TTN gene, c.100126A>G (p.Thr33376Ala), in a family whose members suffer from familial dilated cardiomyopathy in Hubei province. TTN is closely related to dilated cardiomyopathy and is an important causative gene of familial dilated cardiomyopathy.
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http://dx.doi.org/10.1016/j.gene.2017.11.001DOI Listing
February 2018

Renal Sympathetic Denervation in Rats Ameliorates Cardiac Dysfunction and Fibrosis Post-Myocardial Infarction Involving MicroRNAs.

Med Sci Monit 2016 Aug 4;22:2751-60. Epub 2016 Aug 4.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (mainland).

BACKGROUND The role of renal sympathetic denervation (RSD) in ameliorating post-myocardial infarction (MI) left ventricular (LV) fibrosis via microRNA-dependent regulation of connective tissue growth factor (CTGF) remains unknown. MATERIAL AND METHODS MI and RSD were induced in Sprague-Dawley rats by ligating the left coronary artery and denervating the bilateral renal nerves, respectively. Norepinephrine, renin, angiotensin II and aldosterone in plasma, collagen, microRNA21, microRNA 101a, microRNA 133a and CTGF in heart tissue, as well as cardiac function were evaluated six weeks post-MI. RESULTS In the RSD group, parameters of cardiac function were significantly improved as evidenced by increased LV ejection fraction (p<0.01), LV end-systolic diameter (p<0.01), end-diastolic diameter (p<0.05), LV systolic pressure (p<0.05), maximal rate of pressure rise and decline (dP/dtmax and dP/dtmin, p<0.05), and decreased LV end-diastolic pressure (p<0.05) when compared with MI rats. Further, reduced collagen deposition in peri-infarct myocardium was observed in RSD-treated rats along with higher microRNA101a and microRNA133a (p<0.05) and lower microRNA21 expression (p<0.01) than in MI rats. CTGF mRNA and protein levels were decreased in LV following RSD (p<0.01), accompanied by decreased expression of norepinephrine, renin, angiotensin II and aldosterone in plasma (p<0.05) compared with untreated MI rats. CONCLUSIONS The potential therapeutic effects of RSD on post-MI LV fibrosis may be partly mediated by inhibition of CTGF expression via upregulation of microRNA 101a and microRNA 133a and downregulation of microRNA21.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982530PMC
http://dx.doi.org/10.12659/msm.898105DOI Listing
August 2016

The roles of a novel inflammatory neopterin in subjects with coronary atherosclerotic heart disease.

Int Immunopharmacol 2015 Feb 25;24(2):169-172. Epub 2014 Nov 25.

Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.

Coronary atherosclerotic heart disease (CHD) is currently regarded as a chronic inflammatory disease. The inflammatory cytokine neopterin (NP) is a new predictor of the stable type of atherosclerotic plaque, and this study focused on the relationship between neopterin, Gensini score and high-sensitivity C-reactive protein (Hs-CRP) to explore the important role of neopterin in patients with CHD. This study enrolled 176 patients into the control group and 266 patients into the experimental group. The Gensini score was used to assess the severity of the coronary lesions, enzyme-linked immunosorbent assays (ELISAs) were used to measure the serum NP level, and other indicators were assessed using a fully automatic biochemical analyzer. The data were analyzed using SPSS19.0 statistical software. The serum NP level was higher in the experimental group than in the control group (132.23±6.40ng/mL vs. 40.95±2.67ng/mL, P<0.001). Compared with the stable angina (SA) group, the serum NP level was significantly increased in the unstable angina (UA) group (135.99±12.45ng/mL) and the acute myocardial infarction (AMI) group (173.66±13.59ng/mL) (P<0.05). In addition, the serum NP level was positively correlated with the Gensini score (r=0.687, P<0.001) as well as with the level of Hs-CRP (r=0.190, P<0.001). The serum level of NP was significantly higher in patients with CHD and was positively correlated with the severity of CHD. Thus, NP may become a new indicator for the assessment of the inflammatory response in coronary atherosclerosis.
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http://dx.doi.org/10.1016/j.intimp.2014.11.013DOI Listing
February 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

Improved biocompatibility of poly(lactic-co-glycolic acid) orv and poly-L-lactic acid blended with nanoparticulate amorphous calcium phosphate in vascular stent applications.

J Biomed Nanotechnol 2014 Jun;10(6):900-10

Biodegradable polymers used as vascular stent coatings and stent platforms encounter a major challenge: biocompatibility in vivo, which plays an important role in in-stent restenosis (ISR). Co-formulating amorphous calcium phosphate (ACP) into poly(lactic-co-glycolic acid) (PLGA) or poly-L-lactic acid (PLLA) was investigated to address the issue. For stent coating applications, metal stents were coated with polyethylene-co-vinyl acetate/poly-n-butyl methacrylate (PEVA/PBMA), PLGA or PLGA/ACP composites, and implanted into rat aortas for one and three months. Comparing with both PEVA/PBMA and PLGA groups after one month, the results showed that stents coated with PLGA/ACP had significantly reduced restenosis (PLGA/ACP vs. PEVA/PBMA vs. PLGA: 21.24 +/- 2.59% vs. 27.54 +/- 1.19% vs. 32.12 +/- 3.93%, P < 0.05), reduced inflammation (1.25 +/- 0.35 vs. 1.77 +/- 0.38 vs. 2.30 +/- 0.21, P < 0.05) and increased speed of re-endothelialization (1.78 +/- 0.46 vs. 1.17 +/- 0.18 vs. 1.20 +/- 0.18, P < 0.05). After three months, the PLGA/ACP group still displayed lower inflammation score (1.33 +/- 0.33 vs. 2.27 +/- 0.55, P < 0.05) and higher endothelial scores (2.33 +/- 0.33 vs. 1.20 +/- 0.18, P < 0.05) as compared with the PEVA/PBMA group. Moreover, for stent platform applications, PLLA/ACP stent tube significantly reduced the inflammatory cells infiltration in the vessel walls of rabbit iliac arteries relative to their PLLA cohort (NF-kappaB-positive cells: 23.31 +/- 2.33/mm2 vs. 9.34 +/- 1.35/mm2, P < 0.05). No systemic biochemical or pathological evidence of toxicity was found in either PLGA/ACP or PLLA/ACP. The co-formulation of ACP into PLGA and PLLA resulted in improved biocompatibility without systemic toxicity.
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http://dx.doi.org/10.1166/jbn.2014.1856DOI Listing
June 2014