W13.5 The role of different pathways in aortic vasodilatation in the low-dose endotoxin rat model for preeclampsia

Abstract

The new adipocytokine visfatin is closely associated with the cardiovascular diseases, and expression of visfatin is elevated in the heart failure patients. However, at the cellular level, little work has been done on visfatin expression in the cardiomyocyte hypertrophy. Here, the authors investigated the expression and mechanisms of visfatin in angiotensin II (Ang II)-induced cardiomyocyte hypertrophy in vitro by means of the cultured neonatal rat cardiomyocytes.After primary culture of 2- to 3-day-old Sprague–Dawley rat cardiomyocytes and cardiac fibroblasts, cardiomyocytes were pretreated with Ang II. Ang II type-1 receptor (AT1-R) antagonist telmisartan and Ang II type-2 receptor antagonist PD123319 were used to block effects of Ang II. These inhibitors used for the AT1-R pathway determination included SP600125, AG490 and U0126. Cell viability was examined using the 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The expression of visfatin was examined by means of reverse transcription-polymerase chain reaction and Western blot. The expression of brain natriuretic peptide was examined through western-blot analysis.Visfatin was found expressed in cardiomyocytes as well as cardiac fibroblasts, and there was no significant difference at the mRNA and protein levels of visfatin. Ang II treatment induced the increased expression of visfatin and brain natriuretic peptide in a dose- and time-dependent manner in cardiomyocytes, and pretreatment with AT1-R antagonist telmisartan completely blocked Ang II-induced visfatin expression increasement. The increased visfatin expression was also blocked by the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway inhibitor AG490.Visfatin expression was increased mainly through the AT1-R-JAK/STAT pathway in the process of Ang II-induced cardiomyocyte hypertrophy.