Cholesterol homeostasis and high-density lipoprotein formation in arterial smooth muscle cells.
The balance between lipid accumulation and removal from cells in the artery wall is a key factor in atherogenesis. Smooth muscle cells (SMCs) are the main cell type in human intimal thickenings and some stages of atherosclerosis; however, cholesterol homeostasis in these cells has received little attention when compared with intimal macrophages. In addition, it has been demonstrated that SMCs may change phenotype to express macrophage markers upon cholesterol loading, indicating that a large portion of what are considered monocyte-derived human macrophages in human lesions may actually have originated as SMCs. We have recently reported low expression of the key regulator of cholesterol removal to apolipoprotein A-I to form high-density lipoprotein particles, the adenosine-triphosphate-binding cassette transporter A1, in cultured intima-phenotype epithelioid rat SMCs, as well as reduced expression of adenosine-triphosphate-binding cassette transporter A1 in intimal as compared with medial SMCs in human coronary atheromas. These combined observations suggest that SMCs and SMC-derived macrophage-like cells may contribute a much larger amount of the excess cholesterol accumulated in the atherosclerotic intima than previously known. The aim of this review is to present the current state of knowledge of cholesterol homeostasis in arterial SMC and to frame questions requiring further study to understand the relative importance to SMCs in overall atheroma lipid metabolism.
Department of Medicine, Providence Heart and Lung Institute, St. Paul's Hospital, Vancouver,BC, Canada V6Z 1Y6.
Sima
S
Allahverdian
Gordon A
GA
Francis
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D001158:Arteries / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D001692:Biological Transport; D054338:Cell Transdifferentiation; D002784:Cholesterol / Q000378:metabolism*; D005487:Foam Cells / Q000378:metabolism / Q000473:pathology; D006706:Homeostasis; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D051381:Rats
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D002784:Cholesterol