Abstract
Background - Recent data have indicated that estradiol can modulate the kinetics of endothelial progenitor cells (EPCs) via endothelial nitric oxide synthase (eNOS)-dependent mechanisms. We hypothesized that estradiol could augment the incorporation of bone marrow (BM)-derived EPCs into sites of ischemia-induced neovascularization, resulting in protection from ischemic injury. Methods and Results - Myocardial infarction (MI) was induced by ligation of the left coronary artery in ovariectomized mice receiving either 17β-estradiol or placebo. Estradiol induced significant increases in circulating EPCs 2 and 3 weeks after MI in estradiol-treated animals, and capillary density was significantly greater in estradiol-treated animals. Greater numbers of BM-derived EPCs were observed at ischemic sites in estradiol-treated animals than in placebo-treated animals 1 and 4 weeks after MI. In eNOS-null mice, the effect of estradiol on mobilization of EPCs was lost, as was the functional improvement in recovery from acute myocardial ischemia. A decrease was found in matrix metalloproteinase-9 (MMP-9) expression in eNOS-null mice under basal and estradiol-stimulated conditions after MI, the mobilization of EPCs by estradiol was lost in MMP-9-null mice, and the functional benefit conferred by estradiol treatment after MI in wild-type mice was significantly attenuated. Conclusions - Estradiol preserves the integrity of ischemic tissue by augmenting the mobilization and incorporation of BM-derived EPCs into sites of neovascularization by eNOS-mediated augmentation of MMP-9 expression in the BM. Moreover, these data have broader implications with regard to our understanding of the role of EPCs in post-Mi recovery and on the sex discrepancy in cardiac events.
Original language | English (US) |
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Pages (from-to) | 1605-1614 |
Number of pages | 10 |
Journal | Circulation |
Volume | 113 |
Issue number | 12 |
DOIs | |
State | Published - Mar 2006 |
Keywords
- Angiogenesis
- Endothelium
- Myocardial infarction
- Nitric oxide synthase
- Stem cells
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)