Heat shock protein 27 modification is increased in the human diabetic failing heart.

Chronic conditions like diabetes mellitus (DM) leading to altered metabolism might cause cardiac dysfunction. Hyperglycemia plays an important role in the pathogenesis of diabetic complications including accumulation of methylglyoxal (MG), a highly reactive alpha-dicarbonyl metabolite of glucose degradation pathways and increased generation of advanced glycation endproducts (AGEs). The aim of this investigation was to study the extent of the MG-modification argpyrimidine in human diabetic heart and in rat cardiomyoblasts grown under hyperglycemic conditions. Left ventricular myocardial samples from explanted hearts of patients with cardiomyopathy with (n=8) or without DM (n=8) as well as nonfailing donor organs (n=6), and rat cardiac myoblasts H9c2 treated with glucose were screened for the MG-modification argpyrimidine. The small heat shock protein 27 (Hsp27) revealed to be the major argpyrimidine containing protein in cardiac tissue. Additionally, the modification of arginine leading to argpyrimidine and the phosphorylation of Hsp27 are increased in the myocardium of patients with DM. In H9c2 cells hyperglycemia leads to a decrease of the Hsp27-expression and an increase in argpyrimidine content and phosphorylation of Hsp27, which was accompanied by the induction of oxidative stress and apoptosis. This study shows an association between diabetes and increased argpyrimidine-modification of myocardial Hsp27, a protein which is involved in apoptosis, oxidative stress, and cytoskeleton stabilization.

[Diabetic cardiomyopathy--a type of coronary artery disease?]. / Diabetische Kardiomyopathie: Eine Variante der koronaren Herzkrankheit?

Diabetic cardiomyopathy is a myocardial disease caused by diabetes mellitus unrelated to vascular and valvular pathology or systemic arterial hypertension. Clinical and experimental studies have shown that diabetes mellitus causes myocardial hypertrophy, apoptosis and necrosis, and increases interstitial tissue. The pathophysiology of diabetic cardiomyopathy is incompletely understood and several mechanistical approaches are under debate. Metabolic impairments like hyperglycemia, hyperlipidemia, hyperinsulinemia, and alterations in the cardiac metabolism lead to structural and functional changes which show cellular effects leading to increased oxidative stress, interstitial fibrosis, myocyte death, and disturbances in ion transport and homeostasis. Diastolic dysfunction which consecutively results in systolic dysfunction with increased left ventricular volume and reduced ejection fraction is an early diagnostic parameter. Treatment of diabetic cardiomyopathy does not differ from myocardiopathies of other etiologies and therefore has to follow the appropriate guidelines. Early intervention to reverse metabolic toxicity is the most effective method of prevention.