Aim: 

Diabetic cardiomyopathy (DCM) may cause treatment-resistant heart failure (HF) in the diabetic population but the multifaceted mechanism underlying cardiac dysfunction is still unclear. Stem-cell therapy, an emerging strategy to prevent HF in myocardial infarction, has not yet been evaluated in DCM. To address this issue, we analyzed the role of hyperglycaemia-induced cardiac stem cell (CSC) disease in the pathophysiology of DCM.

Methods: 

A rat model of Streptozotocin-induced diabetes was studied at 1-to-4 weeks of hyperglycaemia. Cardiac electromechanical properties were assessed in intact animals, and at tissue-cellular levels. Functional measurements were related to (i) ventricular remodelling, (ii) CSC number, distribution and death/proliferation ratio, and (iii) myocyte regeneration rate.

Results: 

The first detrimental effect of metabolic alterations was constituted by a marked loss of ventricular mass (-20%) which triggered changes in CSC compartment (at 1 week). As compared to normal hearts, an increased rate of DNA replication and mitotic divisions as well as generation of new cardiomyocytes properly integrated with the spared surrounding tissue characterized the subsequent asymptomatic phases of diabetes (2–3 weeks). These compensatory mechanisms contributed to limit structural remodelling and to preserve ventricular performance. After 3–4 weeks, the progressive impairment of CSC storage and the decreased cell-proliferation/cell-death ratio led to the DCM phenotype.

Conclusions: 

Preserving the functional pool of cardiac progenitor cells and increasing their regenerative capacity may constitute an innovative therapeutic option to prevent and treat DCM.