Abstract 12181: Locally Applied Suramin inhibits Angiogenesis in Adventitia and Arterial Lesion Progression in Apolipoprotein E-deficient Mice
Background:Exaggerated formation of vasa vasorum (VV) plays an important role in the pathogenesis of atherosclerosis. Augmented angiogenesis by locally administrated basic fibroblast growth factor in adventitia promotes atherosclerotic lesion formation in ApoE-deficient (ApoE-/-) mice. A growth factor inhibitor suramin inhibits graft vasculopathy in mice by suppression of smooth muscle cell proliferation. However, it remains unclear whether locally applied suramin in adventitia decreases VV formation and atherosclerotic lesion progression without mechanical vascular injury.
Methods:First, the existence of atherosclerotic lesions and VV formation in femoral arteries (FAs) of old ApoE-/- mice was evaluated. Male 7-week-old ApoE-/- mice (n=5) were fed western type diet. At 48 to 52-week-old, FAs of both sides were harvested and microvessels in adventitia were visualized by perfusion staining with Lycopersicon Esculentum (Tomato) lectin. Next, using another group of ApoE-/- mice (n=12), suramin loaded poly lactic/glycolic acid in pluronic-127 gel solution (the total amount of suramin was 1.1μ g for one FA) was administered in adventitial spaces of the right FAs at 40-week-old. Gel alone was put around the left FAs of the mice as a control. Ten weeks after the operation, FAs were harvested and observed after microvessel staining with Tomato lectin.
Results:Atherosclerotic lesions with increased VV were detected in six of 10 FAs in old ApoE-/- mice. Observation of five different sections (100μ m pitch) from each FAs revealed that suramin applied in adventitia decreased atherosclerotic lesion formation (13 of 60 sections of the left FAs and 4 of 60 sections of the right FAs had lesions, lesion areas were 1.36x104 ± 0.71 x104 μ m2, 0.31x104 ± 0.25 x104 μ m2 respectively). VV formation and inflammatory cell accumulation were observed in adventitia outside of the lesions. VV formation was not detected around the arteries without lesions.
Conclusions:VV proliferation might contribute to lesion development in femoral arteries of ApoE-/- mice. Locally applied suramin inhibits adventitial angiogenesis and atherosclerotic lesion progression under hypercholesterolemia without mechanical vascular injury.
- © 2012 by American Heart Association, Inc.