Effect of irbesartan on angiotensin II-induced adiponectin expression in human cardiomyocytes

Background: Excessive angiotensin II (AngII) can cause cardiac dysfunction and failure. Adiponectin is an abundant plasma protein secreted from adipocytes that elicits protective effects in the vasculature and myocardium. We therefore hypothesized that AngII may induce the expression of adiponectin in cultured human cardiomyocytes (HCM), and adiponectin expression could perhaps be modified by angiotensin type 1 receptor blocker (ARB) irbesartan. Methods: The HCM were stimulated either with or without AngII, and the inhibitory effects of irbesartan on adiponectin expression were tested. The levels of phosphorylated extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK) proteins induced by AngII, and the effects of specific inhibition on the ERK, p38, and JNK pathways on the AngII-induced adiponectin protein expression were also tested. Results: AngII dose-dependently induced adiponectin expression in HCM. Pretreatment with irbesartan significantly blocked the increase of adiponectin protein by the AngII. AngII significantly increased phosphorylation of ERK, p38, and JNK, while PD98059, SB205380, and SP600125 attenuated the phosphorylation of the 3 signaling pathways, respectively, and adiponectin expression induced by AngII. Conclusion: Our study revealed that AngII enhances adiponectin expression in cultured HCM, probably mediated through the ERK, p38, and JNK pathways. The use of ARB irbesartan can inhibit the AngII-induced adiponectin expression.