Monocyte Recruitment Versus Macrophage Proliferation in Atherosclerosis.

Abstract

Atherosclerosis, the underlying pathology in most cardiovascular disease, is a chronic inflammatory disease,1 characterized by accumulation of macrophages in the subendothelial space. Macrophages are protagonists of the disease, both early in the disease as well as during later stages of atherosclerotic lesion progression, with a continuous turnover of the cells.2 Blood monocytes enter the artery wall and differentiate into macrophages, contributing to atherosclerotic lesion growth,3 but local proliferation and survival of existing artery wall macrophages also contribute to lesional macrophage plaque burden (Figure).2 Figure. Macrophages play an important role in all phases of atherosclerosis. Monocyte recruitment is critical during early atherosclerotic disease (and perhaps during certain other situations; left ), and thus at this stage of the disease, blood monocyte levels are an important determining factor. Local macrophage proliferation dominates macrophage accumulation in later stages of atherosclerosis ( right ). Macrophage protein kinase C (PKC) δ is induced by modified lipids that can be found in the plaque. Myeloid cell PKCδ primarily impairs macrophage survival and proliferation, via regulation of phosphorylation of Akt and Foxo3a and ultimately the apoptotic regulator Bim. Deletion knockout (KO) of PKCδ results in increased proliferation and survival, both in the artery wall and in the spleen resulting in more atherosclerosis and enlargement of the spleen. SMC indicates smooth muscle cells. Article, see p …