C1QTNF6 blocking peptide

C1q/tumor necrosis factor-related protein-6 (CTRP6) is a newly identified adiponectin paralog with modulation effects on metabolism and inflammation. However, the cardiovascular function of CTRP6 remains unknown. This study aimed to determine its role in cardiac fibrosis and explore the possible mechanism. Myocardial infarction (MI) was induced by left anterior descending coronary artery ligation in rats. CTRP6 was mainly expressed in the cytoplasm of adult rat cardiomyocytes and significantly decreased in the border and infarct zones post-MI. Adenovirus-mediated CTRP6 delivery improved cardiac function, attenuated cardiac hypertrophy, alleviated cardiac fibrosis, and inhibited myofibroblast differentiation as well as the expression of collagen I, collagen III, and connective tissue growth factor post-MI. In cultured adult rat cardiac fibroblasts (CFs), exogenous or cardiomyocyte-secreted CTRP6 inhibited, whereas knockdown of CTRP6 facilitated transforming growth factor-beta 1 (TGF-beta 1)-induced expression of alpha-smooth muscle actin, smooth muscle 22 alpha, and profibrotic molecules. CTRP6 had no effect on CFs proliferation but attenuated CFs migration induced by TGF-beta 1. CTRP6 increased the phosphorylation of AMP-activated protein kinase (AMPK) and Akt in CFs and post-MI hearts. Pretreatment with adenine 9-beta-D-arabinofuranoside (AraA), an AMPK inhibitor, or LY294002, a phosphatidylinositol-3-kinase (PI3 K) inhibitor, abolished the protective effect of CTRP6 on TGF-beta 1-induced profibrotic response. Furthermore, CTRP6 had no effect on TGF-beta 1-induced Smad3 phosphorylation and nuclear translocation, whereas significantly decreased TGF-beta 1-induced RhoA activation and myocardin-related transcription factor-A (MRTF-A) nuclear translocation, and these effects were blocked by AMPK or Akt inhibition. In conclusion, CTRP6 attenuates cardiac fibrosis via inhibiting myofibroblast differentiation. AMPK and Akt activation are responsible for the CTRP6-mediated anti-fibrotic effect by targeting RhoA/MRTF-A pathway.

AimsC1q/tumor necrosis factor-related protein-6 (CTRP6) is a novel adipokine and has emerged as an important mediator for lipid and glucose metabolism. However, to date, the relationship between CTRP6 and T2DM in humans has not been demonstrated. Our objective is to investigate the association of circulating CTRP6 with T2DM in a cross-sectional study.Methods118 patients with newly diagnosed T2DM, 98 subjects with impaired glucose tolerant (IGT) and 132 healthy subjects were recruited for this study. OGTT were performed in 48 healthy individuals to investigate the association of CTRP6 with glucose, insulin and other adipokines. Circulating CTRP6, TNF- and Adipoq were measured by ELISA.ResultsIGT and T2DM individuals had higher serum CTRP6 levels than healthy controls (406.2136.6 and 539.1169.7 vs. 354.3 +/- 117.2ng/mL; both P<0.01), whereas serum CTRP6 concentrations were further increased in T2DM patients compared with IGT individuals (P<0.01). Serum CTRP6 levels were found to be related positively to BMI, WHR, FAT%, TC, TG, HbA1c, FBG, 2h-OGTT, fasting insulin (FIns), 2h-Ins, HOMA-IR and TNF-, and negatively with HDL-C and Adipoq in all individuals (P<0.05 or P<0.01). Multivariate logistic regression analysis demonstrated that CTRP6 was correlated with both IGT and T2DM. After an oral glucose challenge, serum CTRP6 concentrations exhibited a similar change with blood glucose, insulin, TNF- and Adipoq.ConclusionsCTRP6 may be a metabolism- and nutrition-related adipokine and may be related to insulin resistance and T2DM.Trial registrations Clinical Trial Registration Number: ChiCTR-OCC-11001422. Registration name: Plasma cytokines and endothelial function in type 2 diabetes