Abstract 405: Vascular Smooth Muscle Cells (VSMCs) from Abdominal Aortic Aneurysms (AAA) Avidly Take Up Oxidized Cholesterol (oxChol) with Unique Responses Compared with VSMCs from Nonaneurysmal Aorta (NAA)

Objective: We sought to determine if VSMCs from AAA respond to oxChol exposure in a manner which may promote aortic matrix damage. Methods: Early passage VSMCs (5x10 5 ) from human AAA, Carotid plaques (CP) and nAA were compared after exposure to media with oxChol for 72 hours. Cells were counted and stained with Oil Red O, and staining was graded on a 0-4 scale, by 5 blinded experts. Conditioned media (CM) was assayed by ELISA for MMP-2, and corrected for cell number (mean±SE). Results: The average grade of Oil Red O stain (Fig 1) of VSMCs from AAA was 2.89 +/- 0.225, CEA plaques was 3.14 +/- 0.151 and nAA was 1.76 +/- 0.258. Cholesterol uptake was significantly different for AAA vs. nAA (p=.015) and CEA vs. nAA (p=.0002), but not between the unstained controls. Cell number (x10 3 ) at harvest after oxChol exposure was significantly greater than media alone for CP (562±48 vs 338±79, P<0.02) and nAA (343±49 vs 250±31), but there was no effect on AAA (339±49 vs 313±43). With exposure to OxChol, MMP-2 concentration in CM from AAA cells was similar to that from CP cells (224±51ng/ml vs. 352±46ng/ml), but production from nAA cells was significantly less than CP (178±61ng/ml, P<0.05) but not compared to AAA. Conclusion: VSMCs from human AAA exposed to oxChol had significantly increased cholesterol uptake, with MMP-2 production comparable to CP cells. Exposure to oxChol resulted in a mitogenic response in the CEA and nAA cells not seen in the AAA cells. Hypercholesterolemia may promote AAA due to pathologic cellular responses of increased cholesterol uptake, decreased growth and increased protease production. Additional studies are needed to clarify these responses.