Foamy Monocytes Form Early and Contribute to Nascent Atherosclerosis in Mice With Hypercholesterolemia. Issue 8 (August 2015)

• Record Type: Journal Article
• Authors: Xu, Lu; Dai Perrard, Xiaoyuan; Perrard, Jerry L.; Yang, Donglin; Xiao, Xinhua; Teng, Ba-Bie; Simon, Scott I.; Ballantyne, Christie M.; Wu, Huaizhu
• Is Part Of: Arteriosclerosis, thrombosis, and vascular biology. Volume 35:Issue 8(2015)
• Publication Date: 2015-08
• Subjects: Arteriosclerosis -- Periodicals; Thrombosis -- Periodicals; Blood-vessels -- Pathophysiology -- Periodicals; Electronic journals; 616.13
• DOI: 10.1161/ATVBAHA.115.305609
• Languages: English
• ISSNs: 1079-5642

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Objective—</title> <p>To examine infiltration of blood foamy monocytes, containing intracellular lipid droplets, into early atherosclerotic lesions and its contribution to development of nascent atherosclerosis.</p> </sec> <sec> <title>Approach and Results—</title> <p>In apoE<sup>–/–</sup> 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<sup>–/–</sup>Apobec1<sup>–/–</sup> (LDb) mice on WD. Based on CD11c and CD36, mouse monocytes were categorized as CD11c<sup>–</sup>CD36<sup>–</sup>, CD11c<sup>–</sup>CD36<sup>+</sup>, and CD11c<sup>+</sup>CD36<sup>+</sup>. The majority of foamy monocytes were CD11c<sup>+</sup>CD36<sup>+</sup>, whereas most nonfoamy monocytes were CD11c<sup>–</sup>CD36<sup>–</sup> or CD11c<sup>–</sup>CD36<sup>+</sup> in apoE<sup>–/–</sup> mice on WD. In wild-type mice, CD11c<sup>+</sup>CD36<sup>+</sup> and CD11c<sup>–</sup>CD36<sup>+</sup>, but few CD11c<sup>–</sup>CD36<sup>–</sup>, monocytes took up cholesteryl ester–rich very low-density lipoproteins (CE-VLDLs) isolated from apoE<sup>–/–</sup> mice on WD, and CE-VLDL uptake accelerated CD11c<sup>–</sup>CD36<sup>+</sup> to CD11c<sup>+</sup>CD36<sup>+</sup> monocyte differentiation. Ablation of CD36 decreased monocyte uptake of CE-VLDLs. Intravenous injection of DiI-CE-VLDLs in apoE<sup>–/–</sup> mice on WD specifically labeled CD11c<sup>+</sup>CD36<sup>+</sup> foamy monocytes, which infiltrated into nascent atherosclerotic lesions and became CD11c<sup>+</sup> 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.</p> </sec> <sec> <title>Conclusions—</title> <p>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.</p> </sec> </abstract>