title: Foamy monocytes form early and contribute to nascent atherosclerosis in mice with hypercholesterolemia.
abstract: OBJECTIVE
  To examine infiltration of blood foamy monocytes, containing intracellular lipid droplets, into early atherosclerotic lesions and its contribution to development of nascent atherosclerosis.
  
  
  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.
authors.affiliation: From the Department of Medicine (L.X., X.D.P., J.L.P., D.Y., C.M.B., H.W.) and Department of Pediatrics (C.M.B., H.W.), Baylor College of Medicine, Houston, TX; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital and Baylor College of Medicine, TX (C.M.B.); Research Center for Human Genetics, Institute of Molecular Medicine, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston (B.-B.T.); Department of Biomedical Engineering, University of California, Davis (S.I.S.); and Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (L.X., X.X.).
authors.forename: Lu
authors.initials: L
authors.lastname: Xu
authors.affiliation: From the Department of Medicine (L.X., X.D.P., J.L.P., D.Y., C.M.B., H.W.) and Department of Pediatrics (C.M.B., H.W.), Baylor College of Medicine, Houston, TX; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital and Baylor College of Medicine, TX (C.M.B.); Research Center for Human Genetics, Institute of Molecular Medicine, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston (B.-B.T.); Department of Biomedical Engineering, University of California, Davis (S.I.S.); and Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (L.X., X.X.).
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Dai Perrard
authors.affiliation: From the Department of Medicine (L.X., X.D.P., J.L.P., D.Y., C.M.B., H.W.) and Department of Pediatrics (C.M.B., H.W.), Baylor College of Medicine, Houston, TX; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital and Baylor College of Medicine, TX (C.M.B.); Research Center for Human Genetics, Institute of Molecular Medicine, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston (B.-B.T.); Department of Biomedical Engineering, University of California, Davis (S.I.S.); and Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (L.X., X.X.).
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Perrard
authors.affiliation: From the Department of Medicine (L.X., X.D.P., J.L.P., D.Y., C.M.B., H.W.) and Department of Pediatrics (C.M.B., H.W.), Baylor College of Medicine, Houston, TX; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital and Baylor College of Medicine, TX (C.M.B.); Research Center for Human Genetics, Institute of Molecular Medicine, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston (B.-B.T.); Department of Biomedical Engineering, University of California, Davis (S.I.S.); and Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (L.X., X.X.).
authors.forename: Donglin
authors.initials: D
authors.lastname: Yang
authors.affiliation: From the Department of Medicine (L.X., X.D.P., J.L.P., D.Y., C.M.B., H.W.) and Department of Pediatrics (C.M.B., H.W.), Baylor College of Medicine, Houston, TX; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital and Baylor College of Medicine, TX (C.M.B.); Research Center for Human Genetics, Institute of Molecular Medicine, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston (B.-B.T.); Department of Biomedical Engineering, University of California, Davis (S.I.S.); and Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (L.X., X.X.).
authors.forename: Xinhua
authors.initials: X
authors.lastname: Xiao
authors.affiliation: From the Department of Medicine (L.X., X.D.P., J.L.P., D.Y., C.M.B., H.W.) and Department of Pediatrics (C.M.B., H.W.), Baylor College of Medicine, Houston, TX; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital and Baylor College of Medicine, TX (C.M.B.); Research Center for Human Genetics, Institute of Molecular Medicine, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston (B.-B.T.); Department of Biomedical Engineering, University of California, Davis (S.I.S.); and Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (L.X., X.X.).
authors.forename: Ba-Bie
authors.initials: BB
authors.lastname: Teng
authors.affiliation: From the Department of Medicine (L.X., X.D.P., J.L.P., D.Y., C.M.B., H.W.) and Department of Pediatrics (C.M.B., H.W.), Baylor College of Medicine, Houston, TX; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital and Baylor College of Medicine, TX (C.M.B.); Research Center for Human Genetics, Institute of Molecular Medicine, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston (B.-B.T.); Department of Biomedical Engineering, University of California, Davis (S.I.S.); and Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (L.X., X.X.).
authors.forename: Scott I
authors.initials: SI
authors.lastname: Simon
authors.affiliation: From the Department of Medicine (L.X., X.D.P., J.L.P., D.Y., C.M.B., H.W.) and Department of Pediatrics (C.M.B., H.W.), Baylor College of Medicine, Houston, TX; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital and Baylor College of Medicine, TX (C.M.B.); Research Center for Human Genetics, Institute of Molecular Medicine, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston (B.-B.T.); Department of Biomedical Engineering, University of California, Davis (S.I.S.); and Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (L.X., X.X.).
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.affiliation: From the Department of Medicine (L.X., X.D.P., J.L.P., D.Y., C.M.B., H.W.) and Department of Pediatrics (C.M.B., H.W.), Baylor College of Medicine, Houston, TX; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital and Baylor College of Medicine, TX (C.M.B.); Research Center for Human Genetics, Institute of Molecular Medicine, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston (B.-B.T.); Department of Biomedical Engineering, University of California, Davis (S.I.S.); and Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (L.X., X.X.). hwu@bcm.edu.
authors.forename: Huaizhu
authors.initials: H
authors.lastname: Wu
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D001018:Aortic Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D039521:CD11c Antigen / Q000235:genetics; D018955:CD36 Antigens / Q000172:deficiency / Q000235:genetics; D002460:Cell Line; D002791:Cholesterol, Dietary; D015243:Cholesterol, VLDL / Q000378:metabolism*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D039521:CD11c Antigen; D018955:CD36 Antigens; D002791:Cholesterol, Dietary; D015243:Cholesterol, VLDL; D011973:Receptors, LDL; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4
keywords: atherosclerosis; diet, high-fat; inflammation; lipoproteins; monocytes