Targeting Immunoliposomes Containing Pro-angiogenic Compounds to the Infarcted Rat Heart

Targeting Immunoliposomes Containing Pro-angiogenic Compounds to the Infarcted Rat Heart

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Heart failure is a major health problem of epidemic proportions. The upregulated expression of endothelial cell adhesion molecules in certain regions of the heart after a myocardial infarction (MI) provides a potential avenue for selectively targeting drugs to inflamed tissue. Liposomes are a clinically relevant vector which have the capacity to carry drugs and whose surface can be modified with antibodies which can preferentially bind to upregulated adhesion molecules found on the surface of inflamed endothelial cells. A myocardial infarction was induced in Sprague-Dawley rats by ligation of the left anterior descending coronary artery (LADA). In the first 24 hours after an MI, we have found P-selectin to be the most effective target for our liposomal drug delivery system. After treatment with liposomes containing VEGF, changes in vasculature post-MI were quantified by immunohistochemistry to demarcate anatomical and perfused vessels. Changes in cardiac function were also measured with echocardiography. Our liposome-based drug delivery system was successful in moderating the loss of vessels in the border zone of the infarcted myocardium and restoring some cardiac function. This treatment increased the number of anatomical vessels in these areas by 21% and the number of perfused vessels by 74%. In addition, this treatment was found to significantly improve several systolic parameters of cardiac function such as left ventricular end diastolic diameter, fractional shortening, and left ventricular wall displacement. Selective targeting of proangiogenic compounds to post-MI tissue can potentially provide the vascular framework for regenerative strategies which aim to restore lost contractile function of the heart through engineering replacement myocardium using approaches such as stem cell therapy.Pulsed-Wave Doppler Measurements Pulsed-Wave Doppler echocardiography was performed using a Philips Sonos 5500 Ultrasound Machine (software package Version D.1) and an S12 Ultrasound Probe. At predetermined times after Ml, anbsp;...


Title:Targeting Immunoliposomes Containing Pro-angiogenic Compounds to the Infarcted Rat Heart
Author:
Publisher:ProQuest - 2008
ISBN-13:

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