Osteoglycin deficiency does not affect atherosclerosis in mice

Abstract

Objective: The small leucine-rich proteoglycan Osteoglycin/Mimecan (OGN) is a component of the extracellular matrix, where it regulates collagen fibrillogenesis and cytokine availability. OGN is abundant in normal vessels and in atherosclerotic and restenotic lesions of rat, rabbit and human arteries. Osteoglycin-null mice show alterations in the thickness of collagen fibers of the cornea and the skin. In this work, we inspect the possible involvement of OGN in the atherosclerosis progression using a double knockout mouse model.

Methods: In order to examine the progression of atherosclerosis in the absence of OGN, we developed double Apoe and Ogn knockout mice and performed a comparative histomorphological and immunofluorescence study of the atherosclerotic lesions of Apoe(-/-)Ogn(-/-) and Apoe(-/-)Ogn(+/+) mice.

Results: We demonstrate the presence of Ogn transcript in the aorta of wildtype mice, its absence in Ogn(-/-) mice, and the normal histomorphology of arteries of Ogn(-/-) mice. The composition of the extracellular matrix and also the cellular content and distribution were similar in atherosclerotic lesions of Apoe(-/-)Ogn(-/-) and Apoe(-/-)Ogn(+/+) mice. Quantification of the lesion size revealed no significant differences between double and single knockout mice. The incidence, size and distribution of calcium deposits were similar in both groups of mice.

Conclusions: The lack of the proteoglycan OGN does not affect the progression of atherosclerosis in mice. Possible causes for the absence of phenotype in the Apoe/Ogn double mutants are discussed.

Keywords: Apoe; Knockout mouse; Osteoglycin; Small Leucine-Repeat Domain Protein.