Before he joined the University of Iowa and became Division Director of Endocrinology and Metabolism, Associate Professor Ayotunde Dokun, MD, PhD, FACE, was principal investigator on a five-year, $1.93M R01 from the National Heart, Lung, and Blood Institute. That NIH grant has traveled with him from Tennessee to Iowa where his work continues investigating possible therapies that could treat peripheral arterial disease (PAD), a condition that occurs when there’s plaque buildup in the arteries and can eventually lead to amputation and death.
“Peripheral arterial disease is a major complication of systemic atherosclerosis, which affects approximately 12 million Americans and puts them at risk for lower extremity amputation and death,” Dokun said. “Current medical treatments target systemic atherosclerosis but are not able to improve perfusion to the ischemic limb and directly treat the problem in PAD. There is a pressing clinical need for therapeutic approaches for PAD.”
Dokun’s previous studies have revealed that a region on mouse chromosome 7, which he termed the limb salvage QTL-1 or LSQ-1, can drive perfusion recovery following vessel occlusion. Within this region his group identified several genes that appear to play a critical role in adaptation to limb ischemic injury in mice. One of these genes is ADAM12.
Dokun aims to identify if a microRNA, known as miR29a, can regulate ADAM12 to improve perfusion recovery following vessel occlusion. He will also test the therapeutic potential of modulating miR29a and ADAM12 expression in limb ischemia. Using an existing human skeletal muscle bio-bank, Dokun will also examine miR29a and ADAM12 expression in skeletal muscles of individuals with and without PAD.
“We have found that diabetes appears to impair regulation of this gene in humans and in rodents such that its expression is blunted in muscles resulting in poor blood flow,” Dokun said. “Therefore, we would like to better understand how this gene works to improve blood flow and determine how to manipulate this for therapy in PAD especially in individuals with diabetes.”