Expansive arterial remodeling is associated with increased neointimal macrophage foam cell content - The murine model of macrophage-rich carotid artery lesions

Article

关键词: MATRIX METALLOPROTEINASES;    ATHEROSCLEROTIC PLAQUES;    BLOOD-FLOW;    INCREASED EXPRESSION;    CORONARY SYNDROMES;    RUPTURE;    CESSATION;    CAPS;   

DOI  :  10.1161/01.CIR.0000016825.17448.11

来源: SCIE

【 摘 要 】

Background-Recent observations associate plaque instability with expansive arterial remodeling, suggesting a common driving mechanism. Methods and Results-To demonstrate that macrophages, a characteristic of vulnerable plaques, also assist in expansive remodeling, we compared carotid artery remodeling due to formation of experimental macrophage-rich and macrophage-poor lesions in the flow cessation model in hypercholesterolemic apolipoprotein E knockout (ApoE KO) and wild type (WT) mice. After ligation, macrophages started to rapidly accumulate in ApoE KO but not in WT carotid artery lesions. Macrophage-rich ApoE KO intimal lesions grew fast, typically occluding within 14 days, despite a tripling of the vessel area. Outward remodeling of macrophage-rich ApoE KO arteries positively correlated with macrophage area (r(2)=0.600, P<0.001). To investigate potential mechanisms of macrophage-enabled expansive remodeling, we compared levels of matrix metalloproteinases in homogenates of macrophage-rich and macrophage-poor carotid arteries. Gelatinolytic activity of macrophage-rich lesions increased faster and reached maximal levels several fold higher than in the macrophage-poor WT lesions. Conclusions-Our results suggest that macrophages facilitate expansive arterial remodeling through increased matrix degradation by matrix metalloproteinases. This initially favorable remodeling action may eventually increase the vulnerability of macrophage-rich atherosclerotic plaques.

【 授权许可】

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