Can a vascular smooth muscle-derived foam-cell really change its spots?

Abstract

Accumulation of lipids within the artery wall is a fundamental feature of atherosclerosis.1 Within vascular cells, lipids accumulate as cytoplasmic droplets of cholesterol esters and triglycerides; cells with an abundance of these droplets are termed foam cells. Macrophages are considered the primary source of foam cells in atherosclerosis.2 However, it has been established for many years that atherosclerotic lesions also contain abundant foam cells with a vascular smooth muscle cell (VSMC) identity.3–5 Consistent with this, VSMCs in culture can accrue neutral lipids when challenged with hyperlipidemic serum or atherogenic lipoproteins.6,7 See accompanying article on page 535 The fate of lipid-laden VSMCs is beginning to be understood, and it would be incorrect to assume that it is identical to that of macrophage foam cells. Incorporation of lipids by macrophages will result in cell death once the macrophage’s capacity to esterify the otherwise toxic free cholesterol is exceeded.8 Macrophage foam cells may also have relatively productive roles within lesions, including phagocytosis and efferocytosis of apoptotic cells, processes critical for limiting the dispersal of lipid and inflammatory products from dying cells.9 In contrast, VSMCs are more resistant than macrophages to the toxicity of free cholesterol.10 As well, their ability to acquire functional characteristics of macrophages is uncertain. A vital role played by healthy VSMCs is to stabilize the vessel wall through the elaboration of fibrils of type I collagen.11 Type I collagen is secreted from the cell as a soluble protein that must then polymerize into insoluble fibrils to confer mechanical properties.12 Although healthy VSMCs orchestrate the brisk assembly of collagen fibrils from soluble precursors,12 until recently it was not known whether VSMC-derived foam cells within lesions were capable of performing this role. This is important given that lesions …