“Peripheral artery disease (PAD) – the narrowing of blood vessels in the limb from plaque build up – is the third leading cause of atherosclerotic cardiovascular mortality. Critical limb ischemia (CLI), is the most severe form of PAD requiring urgent care. Current treatment that focuses on revascularization and/or collateral vessel growth reestablishes blood flow to the limb and temporarily relieves symptoms. These treatments remain ineffective as death rates increase up to 50% within 5 years of diagnosis. This project aims to discover and develop a novel treatment through one of the underlying biological mechanistic changes experienced among PAD patients. PFKFB3 (6-phosphofructo-2-kinase/2,6-bisphosphatase 3) – a bifunctional enzyme regulating an activator molecule within glycolysis – has an established prominent role in the anaerobic energy production of our cells. Research from our lab has shown that CLI patients have decreased skeletal muscle expression of PFKFB3.
This project will undergo a series of mechanistic experiments involving PFKFB3 knockdown and overexpression on different cell lines (muscular vs. vascular). After verifying its functionality and specificity, a stable viral vector will be made to determine statistical and biological outcomes from an animal study involving hindlimb ischemic mice (mimicking conditions in CLI patients). “