title: Exposure of cardiomyocytes to angiotensin II induces over-activation of monoamine oxidase type A: implications in heart failure.
abstract: Several evidences indicate that increased cardiac mitochondrial monoamine oxidase 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-II caused activation of MAO-A and also of catalase and aldehyde dehydrogenase 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 (AT1) 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-II (100 nM for 18 h) in the absence and in the presence of irbesartan (1 μM), an AT1 antagonist. MAO-A catalase and aldehyde dehydrogenase 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 dehydrogenase but not catalase over-activation, were prevented in DLos cells. Similarly, MAO-A activity, but not catalase and aldehyde dehydrogenase increased significantly in HL-1 cells acutely exposed to AT-II and this increase was prevented when irbesartan, an AT1 antagonist was present. Over-activation of cardiomyocyte 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 AT1 antagonists, first line treatments of diabetic cardiomyopathy.
authors.affiliation: Department of Pharmacology, University of Florence, Italy.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Manni
authors.forename: Marina
authors.initials: M
authors.lastname: Zazzeri
authors.forename: Claudia
authors.initials: C
authors.lastname: Musilli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bigagli
authors.forename: Maura
authors.initials: M
authors.lastname: Lodovici
authors.forename: Laura
authors.initials: L
authors.lastname: Raimondi
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006333:Heart Failure / Q000150:complications / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D006943:Hyperglycemia / Q000150:complications; D000077405:Irbesartan; D019808:Losartan / Q000494:pharmacology; D008995:Monoamine Oxidase / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology*; D051381:Rats; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D001713:Biphenyl Compounds; D013777:Tetrazoles; D000804:Angiotensin II; D002374:Catalase; D000444:Aldehyde Dehydrogenase; D008995:Monoamine Oxidase; D000077405:Irbesartan; D019808:Losartan
keywords: Angiotensin type 1 receptor antagonist; Angiotensin-II; Diabetic cardiomyopathy; Heart failure; Monoamine oxidase