Exposure of cardiomyocytes to angiotensin II induces over-activation of monoamine oxidase type A: Implications in heart failure

Several evidences indicate that increased cardiac mitochondrial monoamine oxiclase type A (MAO-A) activity associates with a failing phenotype. Till now, the mechanism underlying such relation is largely unknown. We explored the hypothesis that exposure of cardiomyocytes to AT-Il caused activation of MAO-A and also of catalase and aldehyde clehydrogenase activities, enzymes involved in degrading MAO 's end products. Left ventricular cardiomyocytes were isolated from normoglycemic (N) and streptozotocin-injected (50 mg/kg) rats (D) treated or not treated with losartan (20 mg/kg/day in drinking water; DLos and NLos, respectively), a type 1 receptor (ATO antagonist, for 3 weeks. In each group of cells, MAO, catalase and aldehyde dehydrogenase activities were measured radiochemically and spectrophotometrically. The same enzymes were also measured in HL-1 immortalized cardiomyocytes not exposed and exposed to AT (100 riM for 18 h) in the absence and in the presence of irbesartan (1 15M), an ATi antagonist. MAO -A catalase and aldehyde clehydrogenase activities were found significantly higher in D, than in N cells. MAO -A positively correlated with catalase activity in D cells. MAO -A and aldehyde clehydrogenase but not catalase over activation, were prevented in D, cells. Similarly, MAO -A activity, but not catalase and aldehyde dehyclrogenase increased significantly in HL-1 cells acutely exposed to AT II and this increase was prevented when irbesartan, an ATI antagonist was present. Over activation of card iomyocyte MAO -A activity is among acute (18 h) and short-term (2 weeks of diabetes) cardiac effects of AT II and a novel target of ATI antagonists, first line treatments of diabetic carcliomyopathy. (C) 2013 Elsevier B.V. All rights reserved