title: NG2 Proteoglycan Ablation Reduces Foam Cell Formation and Atherogenesis via Decreased Low-Density Lipoprotein Retention by Synthetic Smooth Muscle Cells.
abstract: OBJECTIVE
  Obesity and hyperlipidemia are critical risk factors for atherosclerosis. Because ablation of NG2 proteoglycan in mice leads to hyperlipidemia and obesity, we investigated the impact of NG2 ablation on atherosclerosis in apoE null mice.
  
  
  RESULTS
  Immunostaining indicates that NG2 expression in plaque, primarily by synthetic smooth muscle cells, increases during atherogenesis. NG2 ablation unexpectedly results in decreased (30%) plaque development, despite aggravated obesity and hyperlipidemia. Mechanistic studies reveal that NG2-positive plaque synthetic smooth muscle cells in culture can sequester low-density lipoprotein to enhance foam-cell formation, processes in which NG2 itself plays direct roles. In agreement with these observations, low-density lipoprotein retention and lipid accumulation in the NG2/ApoE knockout aorta is 30% less than that seen in the control aorta.
  
  
  CONCLUSIONS
  These results indicate that synthetic smooth muscle cell-dependent low-density lipoprotein retention and foam cell formation outweigh obesity and hyperlipidemia in promoting mouse atherogenesis. Our study sheds new light on the role of synthetic smooth muscle cells during atherogenesis. Blocking plaque NG2 or altering synthetic smooth muscle cells function may be promising therapeutic strategies for atherosclerosis.
authors.affiliation: From the Tumor Microenvironment and Cancer Immunology Program, Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA (Z.-G.S., Y.C., H.-B.P., W.H., J.W.S., W.B.S.); and Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Beijing, Republic of China (H.-Z.C.). zgshe@SBPDiscovery.org.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: She
authors.affiliation: From the Tumor Microenvironment and Cancer Immunology Program, Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA (Z.-G.S., Y.C., H.-B.P., W.H., J.W.S., W.B.S.); and Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Beijing, Republic of China (H.-Z.C.).
authors.forename: Yunchao
authors.initials: Y
authors.lastname: Chang
authors.affiliation: From the Tumor Microenvironment and Cancer Immunology Program, Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA (Z.-G.S., Y.C., H.-B.P., W.H., J.W.S., W.B.S.); and Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Beijing, Republic of China (H.-Z.C.).
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Pang
authors.affiliation: From the Tumor Microenvironment and Cancer Immunology Program, Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA (Z.-G.S., Y.C., H.-B.P., W.H., J.W.S., W.B.S.); and Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Beijing, Republic of China (H.-Z.C.).
authors.forename: Wenlong
authors.initials: W
authors.lastname: Han
authors.affiliation: From the Tumor Microenvironment and Cancer Immunology Program, Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA (Z.-G.S., Y.C., H.-B.P., W.H., J.W.S., W.B.S.); and Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Beijing, Republic of China (H.-Z.C.).
authors.forename: Hou-Zao
authors.initials: HZ
authors.lastname: Chen
authors.affiliation: From the Tumor Microenvironment and Cancer Immunology Program, Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA (Z.-G.S., Y.C., H.-B.P., W.H., J.W.S., W.B.S.); and Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Beijing, Republic of China (H.-Z.C.).
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Smith
authors.affiliation: From the Tumor Microenvironment and Cancer Immunology Program, Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA (Z.-G.S., Y.C., H.-B.P., W.H., J.W.S., W.B.S.); and Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Beijing, Republic of China (H.-Z.C.).
authors.forename: William B
authors.initials: WB
authors.lastname: Stallcup
mesh_terms: D000818:Animals; D000941:Antigens / Q000235:genetics; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002478:Cells, Cultured; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005260:Female; D005487:Foam Cells / Q000378:metabolism* / Q000473:pathology; D006949:Hyperlipidemias / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D058226:Plaque, Atherosclerotic; D011509:Proteoglycans / Q000172:deficiency* / Q000235:genetics; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4
keywords: atherosclerosis; chondroitin sulfate proteoglycan 4; foam cells; macrophages; myocytes; smooth muscle