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Eplerenone attenuated cardiac steatosis, apoptosis and diastolic dysfunction in experimental type-II diabetes.

Título : Eplerenone attenuated cardiac steatosis, apoptosis and diastolic dysfunction in experimental type-II diabetes.
Autor : Ramírez, Elisa
Klett-Mingo, Mercedes
Ares-Carrasco, Sara
Picatoste, Belén
Ferrarini, Alessia
Rupérez Pascualena, Francisco Javier
Caro-Vadillo, Alicia
Barbas Arribas, Coral.
Egido, Jesús
Tuñón, José
Lorenzo, Óscar
Materias: Metabolitos.Diabetic cardiomyopathy.Eplerenone.Steatosis.Apoptosis.
Resumen : Background: Cardiac steatosis and apoptosis are key processes in diabetic cardiomyopathy, but the underlying mechanisms have not been elucidated, leading to a lack of effective therapy. The mineralocorticoid receptor blocker, eplerenone, has demonstrated anti-fibrotic actions in the diabetic heart. However, its effects on the fatty-acid accumulation and apoptotic responses have not been revealed. Methods: Non-hypertensive Zucker Diabetic Fatty (ZDF) rats received eplerenone (25 mg/kg) or vehicle. Zucker Lean (ZL) rats were used as control (n = 10, each group). After 16 weeks, cardiac structure and function was examined, and plasma and hearts were isolated for biochemical and histological approaches. Cultured cardiomyocytes were used for in vitro assays to determine the direct effects of eplerenone on high fatty acid and high glucose exposed cells. Results: In contrast to ZL, ZDF rats exhibited hyperglycemia, hyperlipidemia, insulin-resistance, cardiac steatosis and diastolic dysfunction. The ZDF myocardium also showed increased mitochondrial oxidation and apoptosis. Importantly, eplerenone mitigated these events without altering hyperglycemia. In cultured cardiomyocytes, high-concentrations of palmitate stimulated the fatty-acid uptake (in detriment of glucose assimilation), accumulation of lipid metabolites, mitochondrial dysfunction, and apoptosis. Interestingly, fatty-acid uptake, ceramides formation and apoptosis were also significantly ameliorated by eplerenone. Conclusions: By blocking mineralocorticoid receptors, eplerenone may attenuate cardiac steatosis and apoptosis, and subsequent remodelling and diastolic dysfunction in obese/type-II diabetic rats.
Descripción : En: Cardiovascular Diabetology. ESSN. 1475-2840. 2013, 12:172, doi:10.1186/1475-2840-12-172
URI : http://hdl.handle.net/10637/7662
Derechos: http://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
Fecha de publicación : 16-sep-2013
Centro : Universidad San Pablo-CEU
Aparece en las colecciones: Facultad de Farmacia





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