Apoptosis in Patients with Dilated Cardiomyopathy and Diabetes: A Feature of Diabetic Cardiomyopathy?

Abstract

The different findings regarding the presence of apoptotic cells suggest a contribution of pathobiological pathways in the patients with DM to the underlying heart disease.

Increased propensity for cell death in diabetic human heart is mediated by mitochondrial-dependent pathways

“…Increased myocardial cell death is a prominent feature of all cardiomyopathies and is a major determinant in clinical outcomes (24). Given the well-known increase in levels of cell death in diabetic human hearts (14,25,37), we postulated that the source of this increased propensity for cell death may be stressed and/or vulnerable mitochondria. However, serious limitations to studying pathophysiology at the cellular level in human heart exist that make this assessment very difficult.…”

“…diabetes; mitochondria; apoptosis THE PATHOGENIC MECHANISMS by which persistent hyperglycemia and dyslipidemia in diabetes adversely affect the coronary vasculature are well characterized (21), but the mechanisms by which diabetes creates a progressively degenerative state within the myocardium are not as clear. Recently, investigators have focused on the role of myocardial cell death because of the increasing number of studies demonstrating high levels of apoptotic and necrotic cardiomyocytes in experimental models of diabetes (4,23,27) and in cardiac tissue from diabetic patients (14,25,37). Signals initiating myocardial cell death originate from intrinsic (e.g., mitochondria) and extrinsic (e.g., neurohumoral factors) sources (30).…”

Adverse effects of high glucose and free fatty acid on cardiomyocytes are mediated by connective tissue growth factor

“…The effect of various treatments on viable cell number was determined by direct cell counting by hemocytometer using the trypan blue exclusion method as previously described in these cells (27). Dead cells were shown as a distinctive blue color under a microscope while live cells counted did not take up trypan blue.…”

“…Series in type 1 and 2 diabetes report 30 -70% prevalence, using sensitive detection methods by echocardiography (36). Combined structural changes of cardiac myocyte hypertrophy, cell loss, and extracellular matrix (ECM) accumulation (10,11,27,34,40) contribute to diastolic dysfunction (14,28) in DCM.…”

Antiapoptotic effects of GLP-1 in murine HL-1 cardiomyocytes

“…Mechanistically, the complexity of diabetic cardiomyopathy is attributed to abnormal cellular metabolism and defects in organelles such as mitochondria, sarcolemma, and endoplasmic reticulum, all of which may lead to activation of apoptosis (25), a process that contributes to cardiac dysfunction and failure via cardiomyocyte loss and functional derangements of cellular organelles in viable cardiomyocytes (31,32,43). Of interest, it has been reported that diabetic patients with dilated cardiomyopathy had significantly more apoptotic cardiomyocytes compared with nondiabetic patients with dilated cardiomyopathy (24). Furthermore, different experimental studies have shown that blockade of myocardial apoptosis results in significant prevention of diabetesinduced cardiac dysfunction (5,22).…”