The Pathogenesis of Myocardial Fibrosis in the Setting of Diabetic Cardiomyopathy

Abstract

Diabetes has emerged as a major threat to worldwide health. The increasing incidence of diabetes in young individuals is particularly worrisome given that the disease is likely to evolve over a period of years. In 1972, the existence of a diabetic cardiomyopathy was proposed based on the experience with four adult diabetic patients who suffered from congestive heart failure in the absence of discernible coronary artery disease, valvular or congenital heart disease, hypertension, or alcoholism. The exact mechanisms underlying the disease are unknown; however, an important component of the pathological alterations observed in these hearts includes the accumulation of extracellular matrix (ECM) proteins, in particular collagens. The excess deposition of ECM in the heart mirrors what occurs in other organs such as the kidney and peritoneum of diabetics. Mechanisms responsible for these alterations may include the excess production, reduced degradation, and/or chemical modification of ECM proteins. These effects may be the result of direct or indirect actions of high glucose concentrations. This article reviews our state of knowledge on the effects that diabetes-like conditions exert on the cells responsible for ECM production as well as relevant experimental and clinical data.

Enhanced phosphoinositide 3-kinase(p110α) activity prevents diabetes-induced cardiomyopathy and superoxide generation in a mouse model of diabetes

“…Increased PI3K(p110α) activity prevents diabetes-induced increases in cardiomyocyte size, fibrosis and apoptosis Cardiomyocyte hypertrophy, fibrosis and apoptosis all contribute to the pathogenesis and progression of diabetic cardiomyopathy [24,25]. Induction of diabetes in Ntg mice for 12 weeks had no impact on heart weight (HW; see HW/ TL, Table 1) but was associated with increased cardiomyocyte width (≈13%; Fig.…”

Mitochondrial DNA Variant for Complex I Reveals a Role in Diabetic Cardiac Remodeling

“…It is considered that molecular alterations at the myocyte level may be a key factor in the development of myocardial dysfunction. The pathogenesis of ventricular dysfunction has been examined previously in genetic animal models of T2DM (1)(2)(3). Because these models present with a variety of metabolic disorders, it has been impossible to isolate the influence of intrinsic mitochondrial impairments in disease mechanisms.…”

“…Fractional shortening (FS) was calculated as follows: %FS ϭ (end diastolic LV dimension Ϫ end systolic LV dimension)/(end diastolic LV dimension) ϫ 100%. Left ventricular mass (LVM) was calculated using the following formula: LVM ϭ 0.8(1.04{(posterior wall thickness ϩ LV internal diameter ϩ anterior thickness) 3 Ϫ LV internal diameter thickness 3 }) ϩ 0.6 (9). Ejection fraction was derived using the Teicholz formula.…”

Anti-inflammatory effects of atorvastatin improve left ventricular function in experimental diabetic cardiomyopathy

“…Several mechanisms, of which the relative significance is still not known, are involved in the pathogenesis of diabetic cardiomyopathy, including myocardial fibrosis, interstitial inflammation and endothelial dysfunction [2][3][4]. Diabetes-associated hyperglycaemia and dyslipidaemia [5] are associated with pro-inflammatory effects, thereby affecting the endothelium.…”