Cartilage oligomeric matrix protein (COMP) in murine brachiocephalic and carotid atherosclerotic lesions

Abstract

Objective: To investigate the hypothesis that COMP can influence the morphology, stability and size of murine atherosclerotic lesions.

Methods: ApoE- and ApoE/COMP-knockout mice were fed a high-fat diet to develop atherosclerotic plaques at lesion sites of three different types; inflammatory and fibrous plaques induced in the carotid artery by low or oscillatory shear stress, respectively, and spontaneously developing plaques in the brachiocephalic artery. The localization of COMP in the plaques and the effect of COMP deficiency on plaque development were evaluated.

Results: COMP immunoreactivity was observed in about half of the investigated plaques from the ApoE null mice, mainly located along the intima-medial border. There were no significant differences in the size of inflammatory and fibrous carotid plaques between the genotypes. Plaques in the brachiocephalic artery from ApoE mice lacking COMP were increased in size with 54%. In these plaques the collagen content was also increased by 48%. There were no differences in relative collagen content in inflammatory and fibrous carotid plaques between genotypes. Polarized light microscopy showed that the increase in total collagen in brachiocephalic plaques was more than proportionally accounted for by an increase in thicker collagen fibrils.

Conclusion: We have shown that COMP deficiency has a significant impact on atherosclerotic plaque morphology and size. Our data also suggest that an altered collagen metabolism may be an important mechanism in this finding.

Keywords: ApoE-KO mouse; Atherosclerosis; COMP; Collagen fibre; Plaque morphology.