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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1413.)
© 2008 American Heart Association, Inc.

Editorials

Macrophage Function and Its Impact on Atherosclerotic Lesion Composition, Progression, and Stability

The Good, the Bad, and the Ugly

Jeffrey G. Dickhout; Sana Basseri; Richard C. Austin

From the Department of Medicine, McMaster University, St. Joseph’s Hospital and the Henderson Research Centre, Hamilton, Ontario, Canada.

Correspondence to Richard C. Austin, PhD, Department of Medicine, McMaster University, Division of Nephrology, St. Joseph’s Hospital, 50 Charlton Street East, Hamilton, Ontario L8P 4A6. E-mail raustin@thrombosis.hhscr.org

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The role of the macrophage is of fundamental interest in understanding atherosclerotic lesion development and thrombogenicity. After differentiation from blood peripheral monocytes, intimal macrophages incorporate modified lipoproteins through the scavenger receptor pathway.¹ This transforms the macrophage into a lipid-rich foam cell which is a hallmark feature of atherosclerosis and leads to lesion expansion. Macrophage activation results in the excretion of proinflammatory and cytotoxic substances,² including peroxynitrite, an early inducer of atherosclerosis through the endoplasmic reticulum (ER) stress pathway.³ Further, the accumulation of free cholesterol or uptake of oxidized LDL induces macrophage apoptosis.⁴ Cytokine release from macrophages augments the inflammatory response and increases lesion size. Cytotoxic substances, including peroxynitrite and tumor necrosis factor (TNF)-, released by the macrophage results in cell death of lesion-resident endothelial and smooth muscle cells, thereby disrupting vessel structure. Macrophages can also alter the extracellular matrix of the vessel by releasing matrix metalloproteinases (MMPs), thereby leading to lesion breakdown and predisposing the lesion to fissure or rupture.⁵ These aspects of the macrophage in atherosclerotic lesion biology drive the progression of the disease and lead to the decomposition of the arterial wall into atheroma, the ugly gruel remaining after foam cell decomposition.

See accompanying articles on pages 1421 and 1429

The macrophage may also have good effects within the blood vessel wall. Macrophages remove debris through the process of phagocytosis.⁶ One aspect of macrophage phagocytosis, namely efferocytosis, is a process that prevents secondary necrosis and inflammation by removing apoptotic bodies before their decomposition.⁷ Efferocytosis has been shown . . . [Full Text of this Article]

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