Targeted Delivery of VEGF after a Myocardial Infarction Reduces Collagen Deposition and Improves Cardiac Function
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The development of adjunctive therapies which attenuate adverse remodeling and improve LV function post myocardial infarction (MI) is of significant clinical interest. Previously, we have shown that targeted delivery of therapeutic vascular endothelial growth factor (VEGF) to the infarct border zone significantly increases vascular perfusion and results in improvements in LV function. In this study, we tested the hypothesis that improvements in cardiac function observed with this novel targeted drug delivery system strongly correlate with reductions in collagen deposition in the scar tissue after an MI. Rats received anti-P-selectin conjugated immunoliposomes containing VEGF immediately post-MI. Over 4 weeks, evolutionary changes in LV geometry and function were correlated with collagen deposition and infarct size quantified by Gomori’s trichrome and picrosirius red staining. Targeted VEGF treated hearts showed a 37% decrease in collagen deposition in the anterior wall, as well as significant improvements in LV filling pressures. Multi-regression analysis showed that the extent of collagen deposition post MI can be predicted by a linear combination of normalized LV mass and ejection fraction. Targeted delivery of VEGF post-MI results in significant decreases in collagen deposition and adverse remodeling. Improvements in cardiac function in this model are related to degree of collagen deposition and extent of scar formation.
KeywordsPro-angiogenic compounds Diastolic function Cardiac remodeling
The human VEGF165A was generously provided by Genentech, Inc., San Francisco, CA.This work was supported by grants from the American Heart Association and the National Heart, Lung and Blood Institute including a minority Mentored Faculty Career Development Award, KO1 HL076570-05 (to Dr. Crabbe).Rabee Cheheltani is a Predoctoral Fellow of the American Heart Association.
Conflict of interest
The authors have no conflicts of interest to report.
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