Study Of 20-Hydroxyeicosatetraenoic Acid In AngiotensinⅡ-induced Cardiomyocyte Apoptosis

Cardiomyocyte apoptosis has been documented in involve in a variety of cardiac stresses including ischemia-reperfusion injury, heart failure and diabetic cardiomyopathy. It is known that both AngiotensinII (AngII) and 20-HETE, catalyzed by CYP450-ωhydroxylase, could induce apoptosis in cardiomyocyte however, the relationship between 20-HETE and Ang II in cardiomyocytes apoptosis process is unclear. Here we show that cardiomyocytes apoptosis induced by AngII was decreased significantly after co-treated with the inhibitor of CYP450-ωhydroxylase(HET0016), which blocked the synthesis of 20-HETE. This conclusion is supported by the following observations: 1)That apoptosis induced in cardiomyocytes by AngII can be significantly reduced by 20-HETE synthase inhibitor HET0016 2) the mitochondrial membrane potential increased by AngII was significantly decreased by HET0016 in cardiomyocytes 3) Co-treatments with HET0016 and AngII significantly inhibited AngII-induced increased of the activity of caspase-3 and HET0016 reduced AngII induced increases in nuclear condensation amount 4) AngII can increase CYP4A1 and 4A3 mRNA expression in cardiomyocytes. CYP4Aprotein levels were significant increased by AngII. These results demonstrate that 20-HETE mediates AngII-induced apoptosis in cardiomyocytes via mitochondria-dependent pathways. These observations provide a new insight into interaction of 20-HETE and angiotensinII in cardiac diseases.