Asprosin contributes to vascular remodeling in hypertensive rats via superoxide signaling.

OBJECTIVE: Proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to vascular remodeling. Asprosin, a newly discovered protein hormone, is involved in metabolic diseases. Little is known about the roles of asprosin in cardiovascular diseases. This study focused on the role and mechanism of asprosin on VSMC proliferation and migration, and vascular remodeling in a rat model of hypertension. METHODS AND RESULTS: VSMCs were obtained from the aortic media of 8-week-old male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Asprosin was upregulated in the VSMCs of SHR. For in vitro studies, asprosin promoted VSMC proliferation and migration of WKY and SHR, and increased Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activity, NOX1/2/4 protein expressions and superoxide production. Knockdown of asprosin inhibited the proliferation, migration, NOX activity, NOX1/2 expressions and superoxide production in the VSMCs of SHR. The roles of asprosin in promoting VSMC proliferation and migration were not affected by hydrogen peroxide scavenger, but attenuated by superoxide scavenger, selective NOX1 or NOX2 inhibitor. Toll-like receptor 4 (TLR4) was upregulated in SHR, TLR4 knockdown inhibited asprosin overexpression-induced proliferation, migration and oxidative stress in VSMCs of WKY and SHR. Asprosin was upregulated in arteries of SHR, and knockdown of asprosin in vivo not only attenuated oxidative stress and vascular remodeling in aorta and mesentery artery, but also caused a subsequent persistent antihypertensive effect in SHR. CONCLUSIONS: Asprosin promotes VSMC proliferation and migration via NOX-mediated superoxide production. Inhibition of endogenous asprosin expression attenuates VSMC proliferation and migration, and vascular remodeling of SHR.

Periostin gene polymorphisms, protein levels and risk of incident coronary artery disease.

Vascular endothelial growth factor and its receptor the kinase domain receptor play critical roles in the pathogenesis of coronary artery disease. Periostin is an up-regulator of kinase domain receptor expression. The purpose of this study was to determine whether polymorphisms in periostin are associated with the risk of coronary artery disease. Two single nucleotide polymorphisms (SNP C-33G, SNP A-953T) within the promoter region were chosen for further analyses. A case-control study was carried out with patients of Han Chinese ethnicity, which consisted of 492 coronary artery disease cases and 498 controls. Genotyping was performed by means of PCR and restriction fragment length polymorphism (PCR-RFLP) and the plasma level of periostin was measured by enzyme-linked immunosorbent assay (ELISA). In our study, the TT genotype of SNP-A953T was present in the general Chinese population (3.5%), but not in the Han Chinese from Beijing Project (HAPMAP CHB). Plasma periostin concentrations were elevated significantly in patients with coronary artery disease (7.96±8.33 nmol/l) compared with those in healthy volunteers (3.93±1.71 nmol/l) (P=0.005). There was a significant correlation between the 953T genotype and the plasma level of periostin (r2=-0.490, P=0.039). The prevalence of the TT genotype in patients was associated with a slightly lower risk of coronary artery disease (OR=0.443, 95% CI=0.200-0.982), but was not significant after correction (OR=0.427, 95% CI=0.146-1.250). The periostin-33G allele frequency was not significantly different in cases versus controls. Our data suggest that plasma periostin level may serve as a biomarker for the risk of coronary artery disease, but the periostin polymorphisms SNPC-33G and SNPA-953T were not significantly associated with the risk of coronary artery disease in this Chinese population. Although a major effect of the SNPs in the periostin genes on coronary artery disease susceptibility was excluded, the effect of the A-953T SNP on susceptibility and protein expression needs further investigation.

Associations among periostin gene polymorphisms, clinical parameters and heart failure: a case-control study in 1104 Chinese individuals.

AIMS: To determine the associations among periostin gene polymorphisms, clinical parameters and heart failure in a Chinese population. METHODS: In total, 464 patients with heart failure and 640 control individuals were included in this study. rs3829365 and rs1028728 were genotyped through PCR and restriction fragment length polymorphism. Multivariate logistic regression was employed to analyze the independent strength of association among clinical parameters, genotypes and heart failure. RESULTS: rs3829365 was associated with heart failure (P = 0.043), whereas rs1028728 was not (P = 0.188). After adjusting for age, sex, hypertension, diabetes mellitus, smoking and hypertriglyceridemia in multivariate logistic regression, we found that CG or GG of rs3829365 [P = 0.015, odds ratio (OR) = 1.88] was an independent risk factor for heart failure and that CG or GG of rs3829365 (P = 0.039, OR = 0.94) and AT or TT of rs1028728 (P = 0.011, OR = 0.68) were significantly protective factors for heart failure in patients who smoked and in patients with hypertriglyceridemia, respectively. Moreover, heart failure in patients with CG or GG genotype of rs3829365 tended to be more severe than in those with CC genotype. CONCLUSION: These findings suggest that rs3829365 of the periostin gene may be helpful to determine the susceptibility to, and severity of, heart failure. The interactions between rs3829365 and smoking and between rs1028728 and hypertriglyceridemia warrant further investigations for underlying mechanisms.