Mechanisms and molecular targets of methylglyoxal in the heart

Determine the specific biological mechanisms and identify the molecular targets by which methylglyoxal acts in cardiac tissue to produce dysfunction, including in the context of diabetic cardiomyopathy.

Background

Methylglyoxal is a reactive dicarbonyl metabolite that accumulates under hyperglycaemic conditions and is implicated in diabetic complications, including diabetic cardiomyopathy. While prior studies have linked methylglyoxal to oxidative stress, apoptosis, and protein glycation, the precise cardiac molecular targets and mechanistic pathways through which methylglyoxal impairs heart function were not established at the outset of this paper.

This work investigates the acute effects of methylglyoxal on ex vivo rat hearts and intracellular calcium handling in neonatal rat cardiomyocytes. The findings suggest that methylglyoxal disrupts calcium homeostasis and implicate calcium channels—particularly L-type channels—as contributors to cardiac dysfunction. Nevertheless, a comprehensive identification of all relevant cardiac molecular targets and a full mechanistic account remain to be determined.