Objectives Oxidative stress induces hypertrophic gene expression and collagen deposition that mediates cardiac hypertrophy and myocardial fibrosis. Vascular peroxidase 1 (VPO1) is a new heme-containing peroxidase, which can utilise hydrogen peroxide (H2O2) generated from co-expressed NADPH oxidase (NOX) to produce hypochlorous acid (HOCl) and catalyse peroxidative reactions. Our previous studies had found that NOX/VPO1 pathway-mediated oxidative stress plays an important role in myocardial ischaemia-reperfusion injury. This study was aim to investigate whether VPO1 mediate angiontensin II induced cardiac hypertrophy in H9c2 cells and to explore the underlying mechanism.
Methods Cultured H9c2 cells were treated with angiotensin II, cell hypertrophy were measured by cellular surface size, brain natriuretic peptide (BNP) and atrial natriuretic factor (ANF) gene expression. The effects of NADPH oxidase inhibitor, diphenyleneiodonium (DPI), hydrogen peroxide scavenger, catalase, VPO1 inhibitor 4-aminobenzoic acid hydrazide (ABAH) on cell hypertrophy, VPO1 expression, H2O2 and HOCl production were measured. And the effect of ABAH on the mitogen-activated protein kinase pathway including p-38, p-JNK and p-ERK were determined.
Results Angiotensin II treatment significantly increased the cellular size and the gene expression of BNP, ANF while up-regulated the VPO1 expression and HOCl production. These effects were inhibited by pretreatment with DPI, catalase and ABAH. Moreover, pretreatment with ABAH abolished the angiotensin II-induced up-regulation of p-ERK activity, not p-38, p-JNK expression.
Conclusions These results indicated that VPO1 play a role in anngitotensin II induced cell hyperthrophy via NOX-H2O2-VPO1-HOCl-ERK1/2 pathway.
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