Emigration of monocyte-derived cells from atherosclerotic lesions characterizes regressive, but not progressive, plaques

Abstract

Some monocytes normally take up residence in tissues as sessile macrophages, but others differentiate into migratory cells resembling dendritic cells that emigrate to lymph nodes. In an in vitro model of a vessel wall, lipid mediators lysophosphatidic acid and platelet-activating factor, whose signals are implicated in promoting atherosclerosis, blocked conversion of monocytes into migratory cells and favored their retention in the subendothelium. In vivo studies revealed trafficking of monocyte-derived cells from atherosclerotic plaques during lesion regression, but little emigration was detected from progressive plaques. Thus, progression of atherosclerotic plaques may result not only from robust monocyte recruitment into arterial walls but also from reduced emigration of these cells from lesions.

Integrin αDβ2, an adhesion receptor up-regulated on macrophage foam cells, exhibits multiligand-binding properties

“…A recent report suggests that not only the recruitment of monocytes, but also their retention within atherosclerotic lesions, contributes to plaque development. 42 Whether integrin ␣ D ␤ 2 increases monocyte adhesiveness and thus contributes to their retention in the evolving plaque remains to be established.…”

Gene expression changes in foam cells and the role of chemokine receptor CCR7 during atherosclerosis regression in ApoE-deficient mice

“…As a control, an aortic segment was transplanted into an apoE Ϫ/Ϫ mouse. By 1 month, in the regression environment (WT recipient), essentially all of the foam cells disappeared from plaques (4), with many no longer visible after 3 days (5). In contrast, in the progression environment (apoE Ϫ/Ϫ recipient), plaque size and foam cell content increased over time.…”

Macrophages of genetically characterized familial hypercholesterolaemia patients show up‐regulation of LDL‐receptor‐related proteins

“…Macrophages CD16 + are usually related to a mature M2‐phenotype, also characterized for being positive for CD163 20 a scavenger receptor of the haemoglobin–haptoglobin complex involved in haeme catabolism through a process mediated by regulation of the haeme oxygenase‐1 (HMOX1) expression 79. The presence of CD163 macrophages in human atherosclerotic lesions has been also associated with anti‐inflammatory properties mediated through IL10 21, and studies in mice ApoE −/− models have associated plaque regression with the presence of M2 macrophage expressing CD163 80, 81, 82. Although differentiation of monocytes into macrophages is likely to be terminal, macrophages have the ability to switch phenotype and functional characteristics in response to external signals.…”