Lipoproteins in diabetes and myocardial infarction

Individuals with diabetes have a two- to three-fold increased risk of cardiovascular disease, and two-thirds of patients with myocardial infarction have either diabetes or impaired glucose regulation. Metabolic inflexibility with increased utilization of fatty acids as the oxidative energy source has been proposed to contribute to the impaired cardiac function, and has also been linked to worsened outcome in the reperfusion phase after an ischemic event. The mechanism for this is not clear and requires further research. There is also a need to find intervention strategies to reduce the severity of myocardial infarctions.

We have shown that the apolipoprotein A-I (ApoA-I, the major protein of high-density lipoprotein HDL),prevents hyperglycemia by activation of glucose uptake by skeletal and cardiac muscle, and by priming pancreatic beta cells for improved glucose-stimulated insulin secretion. In addition, clinical formulations of ApoA-I with phospholipids has recently shown promise in the treatment of myocardial infarction.

With relevance for individuals at high cardiometabolic risk and/or with diabetes, we aim to investigate the biology and therapeutic potential to restore metabolic flexibility in the heart, as well as to explain the mechanism-of-action in improved insulin secretion and islet function.