[Frontiers in Bioscience 13, 3621-3636, May 1, 2008]
Atherosclerosis as a disease of failed endogenous repair
Andrey G. Zenovich1, Doris A. Taylor2
1Center for Cardiovascular Repair, University of Minnesota, Minneapolis, MN, 55455, 2Medtronic Bakken Professor of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN, 55455
TABLE OF CONTENTS
As coronary artery disease (CAD) continues to be the primary cause of mortality, a more in-depth understanding of pathophysiology and novel treatments are being sought. The past two decades have established inflammation as a driving force behind CAD - from endothelial dysfunction to heart failure. Recent advances in stem/progenitor cell biology have led to initial applications of progenitor cells in CAD continuum and have revealed that atherosclerosis is, at least in part, a disease of failed endogenous vascular repair. Several key progenitor cell populations including endothelial progenitor cells (AC133+/CD34+ population), vascular progenitors (CD31+/CD45low population), KDR+ cells and other bone marrow subtypes are mobilized for vascular repair. However, age and risk factors negatively impact these cells even prior to clinical CAD. Sex-based differences in progenitor cell capacity for repair have emerged as a new research focus that may offer mechanistic insights into clinical CAD discrepancies between men and women. Quantifying injury and cell-based repair and better defining their interactions should enable us to halt or even prevent CAD by enhancing the repair side of the repair/injury equation.