Calf Skeletal Muscle Pathology and Disability in Peripheral Artery Disease

Project: SFRN


  • Mary M McDermott (CD)


Our work shows that people with lower extremity peripheral artery disease (PAD) have greater functional impairment and faster functional decline than people without PAD. However, few medical therapies improve functioning or prevent functional decline in PAD. Growing evidence suggests that ischemia-related calf skeletal muscle pathophysiologic changes contribute to functional decline in PAD. Our preliminary work supports our hypotheses that ischemia causes mitochondrial dysfunction, abnormal autophagy, and other pathologic abnormalities in calf muscle of people with PAD. However, the specific nature of these pathophysiologic changes is poorly defined. Associations of these calf muscle abnormalities with functional decline in PAD are not established. Northwestern's SFRN Center in PAD will use calf muscle biopsy specimens from people with PAD to achieve these goals: a) identify ischemia-related pathologic, metabolic, and mitochondrial abnormalities in people with PAD; b) establish associations of these specific calf muscle abnormalities with mobility loss, and c) identify therapeutic interventions targeting these specific calf muscle abnormalities in order to improve functional performance in people with PAD. Northwestern's SFRN Center in PAD will also identify three talented and dedicated fellows and train them to become leading scientists in the prevention, diagnosis, and treatment of PAD.Titles and Principal Investigators (PI) for each project follow:Basic Project: PI: Christiaan Leeuwenburgh, PhD. Calf muscle mitochondrial dysfunction and impaired autophagy in peripheral artery disease.Clinical Project: PI: Mary McDermott, MD, FAHA. NICotinamidE riboside with and without resveratrol to improve functioning in peripheral artery disease: The NICE TrialPopulation Project: PI: Philip Greenland, MD, FAHA. Mitochondrial dysfunction and disability in peripheral artery disease.Northwestern's training program will be led by Mercedes Carnethon PhD, FAHA.The multidisciplinary investigative team in Northwestern's Center in PAD consists of renowned scientists working together for up to 20 years to improve functional performance in PAD. Northwestern's Center in PAD is ideally positioned to achieve our specific aims, develop new collaborations, and train the next generation of investigators in PAD. Our overall goal aligns with the AHA mission to build healthier lives and prevent disability from cardiovascular disease.
Award amount$874,357.00
Award date04/01/2018
Program typeStrategically Focused Research Network
Award ID18SFRN33900097
Effective start/end date04/01/201803/31/2022