Medial and adventitial macrophages are associated with expansive atherosclerotic remodeling in rabbit femoral artery

Expansive vascular remodeling is considered a feature of vulnerable plaques. Although inflammation is upregulated in the media and adventitia of atherosclerotic lesions, its contribution to expansive remodeling is unclear. We investigated this issue in injured femoral arteries of normo- and hyperlipidemic rabbits fed with a conventional (CD group; n=20) or a 0.5% cholesterol (ChD group; n=20) diet. Four weeks after balloon injury of the femoral arteries, we examined vascular wall alterations, localization of macrophages and matrix metalloproteases (MMP)-1, -2, -9, and extracellular matrix. Neointimal formation with luminal stenosis was evident in both groups, while expansive remodeling was observed only in the ChD group. Areas immunopositive for macrophages, MMP-1, -2 and -9 were larger not only in the neointima, but also in the media and/or adventitia in the injured arterial walls of the ChD, than in the CD group. Areas containing smooth muscle cells (SMCs), elastin and collagen were smaller in the injured arterial walls of the ChD group. MMP-1, -2 and -9 were mainly localized in infiltrating macrophages. MMP-2 was also found in SMCs and adventitial fibroblasts. Vasa vasorum density was significantly increased in injured arteries of ChD group than in those of CD group. These results suggest that macrophages in the media and adventitia play an important role in expansive atherosclerotic remodeling via extracellular matrix degradation and SMC reduction.