Molecular and cellular basis of the aetiology and management of diabetic cardiomyopathy: A short review

Abstract

Diabetes mellitus is one of the most common chronic diseases affecting millions of people worldwide. Cardiovascular complication including myocardial infarction is one of the major causes of death in diabetic patients. Diabetes mellitus induces abnormal pathological findings including cell hypertrophy, neuropathy, interstitial fibrosis, myocytolysis and apoptosis and lipid deposits in the heart. In addition, the cytoplasmic organelles of cardiomyocytes including the plasma membrane, mitochondrion and sarcoplasmic reticulum are also impaired in both type I and type II diabetes. Hyperglycaemia is a major aetiological factor in the development of diabetic cardiomyopathy in patients suffering from diabetes. Hyperglycaemia promotes the production of reactive oxygen (ROS) and nitrogen species (RNS). The release of ROS and RNS induces oxidative stress leading to abnormal gene expression, faulty signal transduction and apoptosis of cardiomyocytes. Hyperglycaemia also induces apoptosis by p53 and the activation of the cytochrome c-activated caspase-3 pathway. Stimulation of connective tissue growth factor and the formation of advanced glycation end products in extracellular matrix proteins induces collagen cross-linking and contribute to the fibrosis observed in the interstitium of the heart of diabetic subjects. In terms of signal transduction, defects in intracellular Ca2+ signalling due to alteration of expression and function of proteins that regulate intracellular Ca2+ also occur in diabetes. All of these abnormalities result in gross dysfunction of the heart. Beta-adrenoreceptor antagonists, ACE inhibitors, endothelin-receptor antagonist (Bonestan), adrenomedullin, hormones (insulin, IGF-1) and antioxidants (magniferin, metallothionein, vitamins C and E) reduce interstitial fibrosis and improve cardiac function in diabetic cardiomyopathy.

Adiponectin Fails in Improving Angiogenic Repair in Streptozocin-Treated or Leprdb/db Mice after Hind Limb Ischemia

“…Our results confirm recent reports in an animal model for Type 1 diabetes, which showed that plasma adiponectin levels are higher in Type 1 diabetic patients than in healthy control subjects [40][41][42]. Follow-up observational studies also showed that higher adiponectin concentrations are associated with an increased risk of incident microvascular complications in Type 1 diabetes [33,34]. This finding was contrary to those reported for the association between adiponectin and macrovascular complications in Type 2 diabetes, as plasma adiponectin levels have repeatedly been shown to be lower in patients with insulin resistance or macrovascular complications than in control subjects [4,35].…”

“…Chronic hyperglycemia leads to microangiopathy, including nephropathy, neuropathy, cardiomyopathy, and peripheral vascular disease [32][33][34][35]. A few studies have examined the efficiency of growth factor-mediated angiogenic repair in these diseases.…”

Transplantation of bone marrow-derived endothelial progenitor cells attenuates myocardial interstitial fibrosis and cardiac dysfunction in streptozotocin-induced diabetic rats

“…At present, conventional therapies for DCM include glycemic control and early administration of neurohormonal antagonists. DCM, however, has yet to be completely prevented (4,5). Therefore, the development of more effective therapeutic strategies for DCM is necessary.…”

Proteomic analysis of age dependent nitration of rat cardiac proteins by solution isoelectric focusing coupled to nanoHPLC tandem mass spectrometry

“…Cardiac proteins are highly susceptible to nitration due to the periodic formation of NO and superoxide, mediating myocardial contractility (Adeghate, 2004;Hare and Stamler, 2005;Saraiva and Hare, 2006). NO can regulate cardiac function through the S-nitrosation of effector molecules such as Ca 2+ ion channels, in particular the plasmalemmal L-type calcium channel and the sarcoplasmic reticulum (SR) ryanodine receptor (RyR) (Hare, 2004;Saraiva and Hare, 2006).…”