Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 29, Issue 6, Pages 802-U56Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.109.186189
Keywords
angiogenesis; collateral circulation; coronary circulation
Categories
Funding
- NIH [HL32788, HL34286, HL 073755, P40-RR17447]
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Objective-We determined whether increasing adherence of multipotent stromal cells (MSCs) would amplify their effects on coronary collateral growth (CCG). Methods and Results-Adhesion was established in cultured coronary endothelials cells (CECs) or MSCs treated with epidermal growth factor (EGF). EGF increased MSCs adhesion to CECs, and increased intercellular adhesion molecule (ICAM-1) or vascular cell adhesion molecule (VCAM-1) expression. Increased adherence was blocked by EGF receptor antagonism or antibodies to the adhesion molecules. To determine whether adherent MSCs, treated with EGF, would augment CCG, repetitive episodes of myocardial ischemia (RI) were introduced and CCG was measured from the ratio of collateral-dependent (CZ) and normal zone (NZ) flows. CZ/NZ was increased by MSCs without treatment versus RI-control and was further increased by EGF-treated MSCs. EGF-treated MSCs significantly improved myocardial function versus RI or RI + MSCs demonstrating that the increase in collateral flow was functionally significant. Engraftment of MSCs into myocardium was also increased by EGF treatment. Conclusions-These results reveal the importance of EGF in MSCs adhesion to endothelium and suggest that MSCs may be effective therapies for the stimulation of coronary collateral growth when interventions are used to increase their adhesion and homing (in vitro EGF treatment) to the jeopardized myocardium. (Arterioscler Thromb Vasc Biol. 2009; 29: 802-808.)
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