apelin-13-peptide and Aortic-Aneurysm--Thoracic

Apelin has been proved to be a critical mediator of vascular function and homeostasis. Here, we investigated roles of Apelin in aortic remodeling and fibrosis in rats with transverse aortic constriction (TAC). Male Sprague-Dawley rats were subjected to TAC and then randomized to daily deliver Apelin-13 (50μg/kg) or angiotensin type 1 receptor (AT1) blocker Irbesartan (50mg/kg) for 4 weeks. Pressure overload resulted in myocardial hypertrophy, systolic dysfunction, aortic remodeling and adventitial fibrosis with reduced levels of Apelin in ascending aortas of rat after TAC compared with sham-operated group. These changes were associated with marked increases in levels of miRNA-122, TGFβ1, CTGF, NFAT5, LGR4, and β-catenin. More importantly, Apelin and Irbesartan treatment strikingly prevented TAC-mediated aortic remodeling and adventitial fibrosis in pressure overloaded rats by blocking AT1 receptor and miRNA-122 levels and repressing activation of the CTGF-NFAT5 and LGR4-β-catenin signaling. In cultured primary rat adventitial fibroblasts, exposure to angiotensin II (100nmolL

Topics: Adventitia; Animals; Aorta; Aortic Aneurysm, Thoracic; beta Catenin; Cardiomegaly; Cells, Cultured; Fibrosis; Intercellular Signaling Peptides and Proteins; Male; MicroRNAs; Myocardium; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled; Transcription Factors; Vascular Remodeling; Ventricular Remodeling; Wnt Signaling Pathway