The Role of microRNA-210 in Regulating Oxidative Stress in Patients with PAD
MicroRNAs (miRs) are small non-coding RNA molecules that function in silencing RNA and in post-transcriptional regulation of gene expression. Recent evidence suggests the role of miR-210 and oxidative stress in the pathophysiology of PAD and its association with mitochondrial function, oxidative metabolism, walking distances and quality of life. This project evaluates the mechanisms by which miR-210 regulates oxidative stress and provides evidence of potential therapeutic strategies.
Our group has quantified, precisely, parameters of myofiber morphology in PAD and control gastrocnemius samples obtained with minimally invasive needle biopsy. With a team of collaborators, we developed a unique technique to quantify changes in gastrocnemius myofiber morphology. We were able to demonstrate for the first time, that objectively defined parameters of gastrocnemius myofiber morphology were closely linked to the calf muscle strength and walking distances of claudicating PAD patients. Furthermore, using statistical modeling, we have demonstrated that advancing myofiber degeneration was associated with increased fibrosis and functional decline in PAD. Finally, we demonstrated that desmin, a cytoskeletal protein responsible for sarcomeric force transmission, accumulates abnormally as aggregates in myofibers of PAD gastrocnemius and is significantly associated with impairment of calf muscle strength.