The National Institutes of Health (NIH) has awarded M. Dennis Leo, PhD, assistant professor in the Department of Physiology at the University of Tennessee Health Science Center (UTHSC), a $1.9 million grant for his project titled “Chloride Channels in Diabetic Vascular Disease.” The study will investigate cellular signaling pathways damaged by diabetes and how they affect the chloride channel, anoctamin-1, found in arterial smooth muscle cells. It will also work to identify promising protein targets for therapeutic intervention. The grant will be distributed over a five-year period.
Diabetes, which afflicts more than 420 million people worldwide, increases the incidence of cardiovascular disease (CVD) almost threefold, leading to significant patient morbidity and mortality. “It’s not just hyperglycemia or insulin deficiency that leads to an increased risk for CVD in diabetics,” Dr. Leo said. “Changes in cellular signaling can cause pathological alterations in vascular function. These are far more complex than previously believed and need to be investigated further.”
Vascular proteins called ion channels are major regulators of arterial contractility. Resistance arteries constrict and dilate to regulate regional organ blood flow and provide cells with sufficient oxygen and nutrients to meet their metabolic needs. The expression and activity of several ion channels that regulate calcium signaling in the vasculature are altered in cardiovascular disease, interfering with normal arterial contractility.
Dr. Leo and his collaborators have found that the cellular checkpoints which normally control the synthesis and regulation of anoctamin-1 are severely damaged. “There are many signaling pathways that intersect to bring about this dysfunction,” Dr. Leo said. “The goal of our study is to uncover how these different factors lead to an increase in arterial anoctamin-1 expression, which is what happens as type II diabetes progresses, and test certain drugs to see if we can modify any of these dysfunctional signaling networks.”