Department of Medicine, UBC James Hogg Research Centre, Providence Heart + Lung Institute at St Paul's Hospital, Room 166, Burrard Building, 1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6.
Cardiovasc Res. 2012 Jul 15;95(2):165-72. doi: 10.1093/cvr/cvs094. Epub 2012 Feb 15.
Smooth muscle cells (SMCs) are the main cell type in intimal thickenings and some stages of human atherosclerosis. Like monocyte-derived macrophages, SMCs accumulate excess lipids and contribute to the total intimal foam cell population. In contrast, apolipoprotein (Apo)E-deficient and LDL receptor-deficient mice develop atherosclerotic lesions that are macrophage- as opposed to SMC-rich. The lesser contribution of SMCs to lesion development in these mouse models has distracted attention away from the importance of SMC cholesterol homeostasis in the artery wall. Intimal SMCs accumulate excess amounts of cholesteryl esters when compared with medial layer SMCs, possibly explained by reduced ATP-binding cassette transporter A1 expression and ApoA-I binding to intimal-type SMCs. The aim of this review is to compare the relative contribution of monocyte-derived macrophages and SMCs to human vs. mouse atherosclerosis, and describe what is known about lipid uptake and removal mechanisms contributing to arterial macrophage and SMC foam cell formation. An increased understanding of the contribution of these cell types to lesion development will help to delineate their relative importance in atherogenesis and as potential therapeutic targets.
平滑肌细胞（SMC）是内膜增厚和人类动脉粥样硬化某些阶段的主要细胞类型。与单核细胞衍生的巨噬细胞一样，SMC 会积累过多的脂质，并促成总内膜泡沫细胞群的形成。相比之下，载脂蛋白（Apo）E 缺陷和 LDL 受体缺陷的小鼠会发展出富含巨噬细胞而非 SMC 的动脉粥样硬化病变。在这些小鼠模型中，SMC 对病变形成的贡献较小，这使得人们对动脉壁中 SMC 胆固醇稳态的重要性关注减少。与中层 SMC 相比，内膜 SMC 积累了过多的胆固醇酯，这可能是由于 ABCA1 表达减少以及 ApoA-I 与内膜型 SMC 的结合所致。本文综述的目的是比较单核细胞衍生的巨噬细胞和 SMC 对人类和小鼠动脉粥样硬化的相对贡献，并描述已知的促进动脉巨噬细胞和 SMC 泡沫细胞形成的脂质摄取和清除机制。增加对这些细胞类型在病变形成中的作用的理解将有助于阐明它们在动脉粥样发生过程中的相对重要性以及作为潜在治疗靶点的作用。
