[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


2. Introduction
3. Endogenous repair: an evolving hypothesis
4. Capacity for endogenous repair decreases with age - fertile ground for atherosclerosis?
5. Risk factors for coronary artery disease: do the signal the "beginning of the end" of endogenous repair?
6. Availability and functional status of progenitor cells throughout the continuum of atherosclerosis
7. Administration of progenitor cells for repair in coronary artery disease: what are the successes and the failures?
8. Sex differences in repair: cell types or immune response?
9. Perspective
10. Acknowledgments
11. References


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.