Associations between Endothelin-1 and Adiponectin in Chronic Heart Failure

Abstract

Objectives: Endothelin-1 (ET-1) induces cardiac hypertrophy, whereas adiponectin may elicit protective effects in the vasculature and myocardium. We therefore evaluated the relationship between plasma ET-1 and adiponectin levels in heart failure (HF) patients, and the association between adiponectin expression and ET-1-induced hypertrophy of human cardiomyocytes (HCM) in vitro. Methods: One hundred seventeen patients with chronic HF were enrolled into this study. A group of 7 patients with end-stage HF undergoing heart transplantation was included in the histopathological study. Baseline clinical evaluations and laboratory measurements were performed. HCM cultures were studied to investigate the effect of ET-1 on cell size and adiponectin expression. Results: Plasma ET-1, adiponectin, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) increased with the severity of HF. Higher New York Heart Association functional class, plasma ET-1, adiponectin, and NT-proBNP levels were significant predictors of adverse outcomes in these patients. The myocardial expression of adiponectin was significantly higher in the recipient hearts of patients undergoing emergency or urgent heart transplantation. In cell culture, ET-1 significantly increased cell size and adiponectin expression in HCM. Conclusions: Adiponectin was significantly elevated in HF and was significantly associated with ET-1. The study provides a basis for further investigation of ET-1 and adiponectin modulation as a therapeutic strategy for ventricular remodeling in HF.

Loss of Mouse P2Y4 Nucleotide Receptor Protects against Myocardial Infarction through Endothelin-1 Downregulation

“…We have focused on this particular target gene because, as described below, we identified in parallel an inflammatory defect in P2Y 4 -null mice. It is known that ET-1 is involved in cardiac inflammation, heart failure, and ventricular remodeling (26). Therefore, we evaluated ET-1 serum level in P2Y 4 +/+ and P2Y 4 2/2 mice during infarction ( Fig.…”

Enhancement of beta-catenin in cardiomyocytes suppresses survival protein expression but promotes apoptosis and fibrosis

“…Certain humoral factors secreted by mechanically stressed cardiomyocytes activate a vast network of intra-and intercellular transduction signals that lead to cardiac dysfunctions [1][2][3][4][5]. Although such abnormalities can be compensated by cardiac hypertrophy, which is a fundamental process of adaptation to an increased workload due to hemodynamic overload [10][11][12], loss of contractile tissue, cardiomyocyte apoptosis and mesenchymal fibrosis will eventually occur [13].…”

“…These factors are able to alter myocardial ultrastructure and determine cardiac fibroblast hypertrophy and/or apoptosis, mesenchymal fibrotic, inflammatory processes and can alter cardiac gene expression [1][2][3][4][5]. This series of events is the basis of myocardial remodeling [6], which is a complex phenomenon of ultrastructural cardiac rearrangement.…”

Nitric oxide/cyclic GMP pathway mediates the endothelin-1-upregulation of adiponectin expression in rat cardiomyocytes

“…Recently, Yin et al (14) suggested that plasma ET-1 and APN increased with the severity of heart failure. APN protein is upregulated in cardiac tissue and is correlated with increased serum concentrations of ET-1, the incubation of HCM with ET-1 significantly increased the protein expression of APN in a time-and dose-dependent manner.…”