Why diabetes patients are at risk of microvascular complications

Researchers have made a breakthrough I understanding why patients with diabetes are at increased risk of microvascular complications, which develop when the body's small blood vessels become diseased.

Investigators from Beth Israel Deaconess Medical Center (BIDMC) have discovered that a molecule called PGC-1alpha - which has previously been shown to spur the growth of blood vessels in muscle - has the opposite effect in the endothelial cells of patients with diabetes, impairing blood vessel growth and leading to dangerous vascular complications.

The new findings not only help explain the molecular mechanisms underlying microvascular disease in diabetes patients, they also suggest that because PGC-1alpha has opposing effects in different cell types, its role as a potential new therapeutic target should be pursued with caution.

With this new research, says senior author Zoltan Arany, MD, PhD, an investigator in BIDMC's CardioVascular Institute and Associate Professor of Medicine at Harvard Medical School (HMS), it is apparent that high levels of blood glucose-the hallmark of diabetes-induces high levels of the PGC-1 alpha molecule in the endothelial cells lining the blood vessels. This, in turn, prevents endothelial cells from properly functioning, inhibiting blood vessel growth.

Through a series of cell culture experiments, as well as experiments in endothelial-specific genetic mouse models, the authors showed that PGC-1alpha in endothelial cells is induced by diabetes, which strongly inhibits endothelial migration and angiogenesis, and leads to vascular dysfunction.

The study has been published in the journal Cell Metabolism.