Targeted Delivery of VEGF after a Myocardial Infarction Reduces Collagen Deposition and Improves Cardiac Function

Abstract

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.

A VEGF delivery system targeting MI improves angiogenesis and cardiac function based on the tropism of MSCs and layer-by-layer self-assembly

“…Moreover, we found that there was improvement in systolic and diastolic function at an early stage; however, angiogenesis did not occur. This finding may be related to the VEGF of myocardial apoptosis and cardiac remodeling [12,46,47] or other factors secreted by MSCs [33,48,49], although angiogenesis does not occur in the early stage. A significant increase in angiogenesis was found after 2 weeks, as has been reported previously [16,50].…”

“…The targeted delivery of an adequate therapeutic dose of VEGF to the infarcted zone is very important [12][13][14][15], as it could promote the formation of new vessels in the infarcted zone while reducing the risk of potential side effects in other tissues. In recent studies, Kiani and his colleagues reported that targeting VEGF-encapsulated immunoliposomes to the MI area of the heart improved vascularity and cardiac function [16].…”

Fourier transform infrared spectroscopy to quantify collagen and elastin in an in vitro model of extracellular matrix degradation in aorta

“…Histology images were acquired using a Nikon microscope equipped with a Nikon DS-Fi1 color camera and Nikon Element software (Nikon Instruments Inc., Mellville, NY). Images of collagen distribution in the picrosirius red stained sections, were obtained under linearly polarized light as detailed previously 50 .…”

Targeted delivery of vascular endothelial growth factor improves stem cell therapy in a rat myocardial infarction model

“…The specificity of Sirius red staining for fibrillar collagen enables sensitive quantitative measurements of collagen content to be performed in locally defined tissue areas. Following our previous work 18 , our quantification of collagen was based on the average intensity of red in the MI area. Although the size of the infarct varies in each sample, quantitative analysis suggests that the percentage of collagen in the MI area decreased significantly with different treatments.…”