So Much Cholesterol: the unrecognized importance of smooth... : Current Opinion in Lipidology (original) (raw)

GENETICS AND MOLECULAR BIOLOGY: Edited by Robert A. Hegele

the unrecognized importance of smooth muscle cells in atherosclerotic foam cell formation

Division of Endocrinology and Metabolism, Centre for Heart Lung Innovation, Providence Healthcare Research Institute, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada

Correspondence to Gordon A. Francis, MD, Division of Endocrinology and Metabolism, Centre for Heart Lung Innovation, Providence Healthcare Research Institute, St. Paul's Hospital, University of British Columbia, Room 166 Burrard Bldg., 1081 Burrard St., Vancouver, BC V6Z 1Y6, Canada. Tel: +1 604 806 9269; e-mail: [email protected]

Abstract

Purpose of review

Smooth muscle cells (SMCs) form the thickened intimal layer in atherosclerosis-prone arteries in early life, and provide the initial site for retention and uptake of atherogenic lipoproteins. Here we review current knowledge regarding the importance of SMCs in the deposition of cholesterol in atherosclerotic plaque.

Recent findings

SMCs were found to comprise at least 50% of total foam cells in human coronary artery atherosclerosis, and exhibit a selective loss of expression of the cholesterol efflux promoter ATP-binding cassette transporter A1. Cholesterol loading induced a loss of SMC gene expression and an increase in macrophage and proinflammatory marker expression by cultured mouse and human arterial SMCs, with reversal of these effects upon removal of the excess cholesterol. Mice engineered to track all cells of SMC lineage indicated that, at most, SMCs make up about one-third of total cells in atherosclerotic plaque in these animals.

Summary

SMCs appear to be the origin of the majority of foam cells in human atherosclerotic plaque. Recent studies suggest a renaissance of research on the role of SMCs in atherosclerosis is needed to make the next leap forward in the prevention and treatment of this disease.