Sustained cardiomyocyte apoptosis and left ventricular remodelling after myocardial infarction in experimental diabetes

Abstract

Aims/hypothesis. Diabetes is known to reduce survival after myocardial infarction. Our aim was to examine whether diabetes is associated with enhanced cardiomyocyte apoptosis and thus interferes with the post-infarction remodelling process in myocardium in rat. Methods. Four weeks after intravenous streptozotocin (diabetic groups) or citrate buffer (controls) injection, myocardial infarction was produced by ligation of left descending coronary artery. Level of cardiomyocyte apoptosis was quantified by TUNEL and caspase-3 methods. Collagen volume fraction and connective tissue growth factor were determined under microscope. Left ventricular dimensions were evaluated by echocardiography and planimetry. Results. The number of apoptotic cardiomyocytes was equally high in diabetic and non-diabetic rats after 1 week from infarction. At 12 weeks after infarction the number of apoptotic cells was higher in the diabetic as compared to non-diabetic rats both in the border zone of infarction and in non-infarcted area. Correspondingly, left ventricular end diastolic diameter, relative cardiac weight, connective tissue growth factorexpression and fibrosis were increased in diabetic compared with non-diabetic rats with myocardial infarction. Conclusion/interpretation. Sustained cardiomyocyte apoptosis, left ventricular enlargement, increased cardiac fibrosis and enhanced profibrogenic connective tissue growth factor expression were detected after myocardial infarction in experimental diabetes. Apoptotic myocyte loss could be an important mechanism contributing to progressive dilatation of the heart and poor prognosis after myocardial infarction in diabetes. [Diabetologia (2004)

Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning

“…STZ administration, the number of apoptotic cardiomyocytes was equally high in diabetic and nondiabetic rats 1 week after induction of permanent coronary occlusion. However, at 12 weeks after infarction the number of apoptotic cells was higher in the diabetic compared with the nondiabetic rats both in the border zone of infarction and in the noninfarcted area (Bä cklund et al, 2004).…”

Ginsenoside Rg1 ameliorates oxidative stress and myocardial apoptosis in streptozotocin-induced diabetic rats

“…CASP3 is a member of the caspase family and has been recognized as an important initiator and promoter of apoptosis. Enhanced apoptosis of cardiomyocytes has been noted after myocardial infarction in experimental diabetes; an increase in CASP3 levels after infarction interfered with the remodeling process in the myocardium of rats (Bäcklund et al, 2004). Diabetes was found to be associated with enhanced apoptosis and necrosis in both ischemic and nonischemic human myocardia, an adverse effect that is mediated, at least in part, by CASP3 (Chowdhry et al, 2007).…”

Role of apoptosis in cardiovascular disease

“…In addition, it has been reported that the mortality of myocardial infarction in diabetic patients is more than double that of non-diabetic patients [27]. It appears that cardiac myocytes in the diabetic myocardium are more susceptible to apoptosis [25], suggesting that the higher sensitivity to MI is due to a higher loss of cardiac myocytes via apoptosis in response to the stress [28]. Also, Kuethe et al [29] found that diabetic patients with dilated cardiomyopathy had significantly more apoptotic cells in the heart compared to patients without diabetes.…”