Objective - To examine infiltration of blood foamy monocytes, containing intracellular lipid droplets, into early atherosclerotic lesions and its contribution to development of nascent atherosclerosis. Approach and Results - In apoE -/- mice fed Western high-fat diet (WD), >10% of circulating monocytes became foamy monocytes at 3 days on WD and >20% of monocytes at 1 week. Foamy monocytes also formed early in blood of Ldlr -/- Apobec1 -/- (LDb) mice on WD. Based on CD11c and CD36, mouse monocytes were categorized as CD11c - CD36 -, CD11c - CD36 +, and CD11c + CD36 +. The majority of foamy monocytes were CD11c + CD36 +, whereas most nonfoamy monocytes were CD11c - CD36 - or CD11c - CD36 + in apoE -/- mice on WD. In wild-type mice, CD11c + CD36 + and CD11c - CD36 +, but few CD11c - CD36 -, monocytes took up cholesteryl ester-rich very low-density lipoproteins (CE-VLDLs) isolated from apoE -/- mice on WD, and CE-VLDL uptake accelerated CD11c - CD36 + to CD11c + CD36 + monocyte differentiation. Ablation of CD36 decreased monocyte uptake of CE-VLDLs. Intravenous injection of DiI-CE-VLDLs in apoE -/- mice on WD specifically labeled CD11c + CD36 + foamy monocytes, which infiltrated into nascent atherosclerotic lesions and became CD11c + cells that were selectively localized in atherosclerotic lesions. CD11c deficiency reduced foamy monocyte infiltration into atherosclerotic lesions. Specific and consistent depletion of foamy monocytes (for 3 weeks) by daily intravenous injections of low-dose clodrosome reduced development of nascent atherosclerosis. Conclusions - Foamy monocytes, which form early in blood of mice with hypercholesterolemia, infiltrate into early atherosclerotic lesions in a CD11c-dependent manner and play crucial roles in nascent atherosclerosis development.
|Original language||English (US)|
|Number of pages||11|
|Journal||Arteriosclerosis, Thrombosis, and Vascular Biology|
|State||Published - Aug 25 2015|
- diet, high-fat
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine