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EXPERIMENTAL STUDY

Effect of human recombinant vascular endothelial growth factor₁₆₅ on progression of atherosclerotic plaque

^a Department of Cardiovascular and Interventional Radiology, Stanford University Medical Center, Stanford, California, USA

Manuscript received August 11, 2000; revised manuscript received February 9, 2001, accepted March 14, 2001.

Reprint requests and correspondence: Dr. Michael D. Dake, Department of Cardiovascular and Interventional Radiology, Room H 3647, Stanford University Medical Center, Stanford, California 94305
mddake{at}stanford.edu

OBJECTIVES

This study was designed to evaluate the impact of recombinant human vascular endothelial growth factor₁₆₅ (rhVEGF) on atherosclerotic plaque progression.

BACKGROUND

Therapeutic angiogenesis represents a promising treatment for ischemic diseases. However, angiogenesis may impact atherosclerosis.

METHODS

Albumin or rhVEGF was administered by a single intramuscular injection (2 µg/kg body weight) to New Zealand White rabbits fed with a 0.25% cholesterol diet beginning three weeks before therapy. Subsets of rabbits from each group underwent perfusion-fixation and harvesting of the thoracic aorta for morphometric and immunohistochemical analyses at 7 or 21 days.

RESULTS

The mean plaque area was 15.75 ± 2.28% and 22.00 ± 3.24% with VEGF and 0.67 ± 0.22% and 1.17 ± 0.34% with albumin at 7 and 21 days, respectively. The plaque circumference was 13.00 ± 2.58% and 23.75 ± 2.86% with VEGF and 2.50 ± 0.65% and 6.25 ± 1.88% with albumin at 7 and 21 days, respectively. The maximal plaque thickness was 0.11 ± 0.002 and 0.15 ± 0.007 mm with VEGF and 0.04 ± 0.009 and 0.07 ± 0.003 mm with albumin at 7 and 21 days, respectively. The endothelial density (reported as percent total plaque area) was 31.75 ± 4.42% and 63.00 ± 8.45% with VEGF and 7.75 ± 1.65% and 12.75 ± 1.93% with albumin at 7 and 21 days, respectively. The macrophage density was 4.5 ± 0.86 and 19.25 ± 1.54 with VEGF and 4.26 ± 0.75 and 6.00 ± 1.08 with albumin at 7 and 21 days, respectively.

CONCLUSIONS

Recombinant human VEGF increases the rate and degree of atherosclerotic plaque formation in the thoracic aorta in a cholesterol-fed rabbit model.

Abbreviations and Acronyms   IgG = immunoglobulin G   rhVEGF = recombinant human vascular endothelial growth factor165

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