Mirabelle Ho, Ottawa Hospital Research Institute
Supervisor: Duncan Stewart, Ottawa Hospital Research Institute
Vascular diseases such as atherosclerosis and stroke are the main cause of mortality for Progeria patients characterized by a premature aging phenotype. Under homeostatic conditions, cell types such as endothelial cells (ECs) are tasked with maintenance of vessel integrity. Progeria patients’ ECs initially undergo hyperproliferation followed rapidly by senescence. Aging ECs are incapable of mediating reparative regenerative process to vasculature subjected to the barrage of atherogenic factors. Thus, restoring proper function to ECs could potentially reverse or ameliorate atherosclerosis. This project proposes the use of ECs derived from iPSCs generated from Progeria patient as a model to understand the molecular mechanisms mediating pathology of premature vascular endothelial aging.
The outcomes of this project will contribute to two of the Network’s areas of priority. ECs derived from
Progeria-iPSCs provide a dynamic platform with which to investigate the initiation and progressive development of vascular disease. Complementing global gene and microRNA (miR) profiling comparison of ECs derived from healthy donors and Progeria patients will accelerate efforts to elucidate the identity of viable novel biomarkers of disease development. This addresses the Network’s desire to identify novel biomarkers of microvascular dysfunction. Furthermore, this approach also permits delineation of signaling pathways involved in vascular disease stemming from senescence. Mechanistic insights into etiology of disease initiation will facilitate the identification of targets for early detection strategies for populations at high risk of vascular disease.