Oxygen Sensing in Endothelial Progenitor Cells

Type of Award: catalyst
Award Number:
Award Period: January 2012 - December 2013
Amount Awarded: $ 200,000.00
PI(s): Jalees Rehman, MD, UIC; David Eddington, PhD, UIC; Navdeep Chandel, PhD, NU;

Abstract: The majority of cardiovascular deaths are due to narrowing of blood vessels (e.g., atherosclerosis) which leads to reduced oxygen supply in vital organs. The discovery of intrinsic "vessel wall repair system" consisting of endothelial progenitor cells (EPCs) raises the possibility of developing novel approaches to treat cardiovascular disease. It is postulated that EPCs activated by tissue hypoxia proliferate and thus repair damaged blood vessels or help build new vessels to restore oxygen supply. A reduction in tissue oxygen content (hypoxia) may be sensed by EPCs, and if true, it constitutes a potent signal to activate EPCs and promote repair of new blood vessels, but it is not known whether and how EPCs sense hypoxia. EPC numbers and activity are often reduced in patients with vascular diseases such as high blood pressure or diabetes, which may explain in part why their EPCs are unable to repair blood vessels or build new blood vessels. Thus, understanding how hypoxia regulates the regenerative potential of EPCs becomes imperative to understand EPC-based treatment in patients with suppressed EPC function. Since little is known about mechanisms underlying oxygen sensing EPCs, by combining the expertise of Drs. Eddington and Rehman at UIC and Dr. Chandel at Northwestern University, we hope to identify novel key regulators of EPC hypoxia activation. Ultimately, we envision this research will lead to therapies that improve EPC function and promote repair of blood vessels.