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Impaired left ventricular relaxation in type 2 diabetic rats is related to myocardial accumulation of N(epsilon)-(carboxymethyl) lysine.
Schäfer, Stefan; Huber, Jochen; Wihler, Cornelia; Rütten, Hartmut; Busch, Andreas E; Linz, Wolfgang.
Afiliación
  • Schäfer S; Therapeutic Department Cardiovascular Diseases, Aventis Pharma Deutschland GmbH, Building H 821, D-65926, Frankfurt am Main, Germany. stefan.schaefer@aventis.com
Eur J Heart Fail ; 8(1): 2-6, 2006 Jan.
Article en En | MEDLINE | ID: mdl-16085456
Myocardial dysfunction in the absence of myocardial ischemia is frequent in patients with diabetes mellitus but the underlying pathomechanism is unclear. We investigated whether accumulation of advanced glycation end products (AGEs) in the diabetic myocardium is related to its functional abnormalities. In 11 male homozygous Zucker diabetic fatty rats (ZDF/Gmi-fa/fa) aged 37 weeks (OBESE) and 11 non-obese, non-diabetic littermates (LEAN), we measured left ventricular function (pressure-volume catheter) and levels of N(epsilon)-(carboxymethyl) lysine (CML), a prototypical AGE, in serum and the left ventricle (competitive enzyme linked immuno-assay). Overt diabetes mellitus (HbA1c > 9%) was present in all OBESE animals but not in LEAN. Systolic left ventricular function was not different between the groups, but the markers of left ventricular relaxation, dP/dt(min) and the relaxation constant tau, were impaired in OBESE. In parallel, CML levels were increased in serum (273 +/- 15 vs. 197 +/- 10 ng/ml, p<0.05) and in the left ventricle (18.4 +/- 1.1 vs. 12.5 +/- 2.0 ng/mg protein, p < 0.05) in OBESE compared to LEAN. There was a linear correlation between tau and the left ventricular CML levels (r = 0.65; p < 0.05). We conclude that type 2 diabetes is associated with predominant left ventricular diastolic dysfunction. Myocardial accumulation of advanced glycation end products may contribute to relaxation abnormalities in type 2 diabetes.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Disfunción Ventricular Izquierda / Diabetes Mellitus Tipo 2 / Lisina / Miocardio Límite: Animals Idioma: En Revista: Eur J Heart Fail Asunto de la revista: CARDIOLOGIA Año: 2006 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Disfunción Ventricular Izquierda / Diabetes Mellitus Tipo 2 / Lisina / Miocardio Límite: Animals Idioma: En Revista: Eur J Heart Fail Asunto de la revista: CARDIOLOGIA Año: 2006 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido