Expression and function of PPARγ in rat and human vascular smooth muscle cells

被引:406
作者
Law, RE
Goetze, S
Xi, XP
Jackson, S
Kawano, Y
Demer, L
Fishbein, MC
Meehan, WP
Hsueh, WA
机构
[1] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Sch Med, Div Endocrinol Diabet & Hypertens, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Sch Med, Div Cardiol, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA
关键词
atherosclerosis; restenosis; growth substances; migration; thiazolidinediones;
D O I
10.1161/01.CIR.101.11.1311
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is activated by fatty acids, eicosanoids, and insulin-sensitizing thiazolidinediones (TZDs). The TZD troglitazone (TRO) inhibits vascular smooth muscle cell (VSMC) proliferation and migration in vitro and in postinjury intimal hyperplasia. Methods and Results-Rat and human VSMCs express mRNA and nuclear receptors for PPAR gamma 1. Three PPAR gamma ligands, the TZDs TRO and rosiglitazone and the prostanoid 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2), all inhibited VSMC proliferation and migration. PPAR gamma is upregulated in rat neointima at 7 days and 14 days after balloon injury and is also present in early human atheroma and precursor lesions. Conclusions-Pharmacological activation of PPAR gamma expressed in VSMCs inhibits their proliferation and migration, potentially limiting restenosis and atherosclerosis. These receptors are upregulated during vascular injury.
引用
收藏
页码:1311 / 1318
页数:8
相关论文
共 33 条
  • [1] Thiazolidinediones produce a conformational change in peroxisomal proliferator-activated receptor-gamma: Binding and activation correlate with antidiabetic actions in db/db mice
    Berger, J
    Bailey, P
    Biswas, C
    Cullinan, CA
    Doebber, TW
    Hayes, NS
    Saperstein, R
    Smith, RG
    Leibowitz, MD
    [J]. ENDOCRINOLOGY, 1996, 137 (10) : 4189 - 4195
  • [2] ACCURATE TRANSCRIPTION INITIATION BY RNA POLYMERASE-II IN A SOLUBLE EXTRACT FROM ISOLATED MAMMALIAN NUCLEI
    DIGNAM, JD
    LEBOVITZ, RM
    ROEDER, RG
    [J]. NUCLEIC ACIDS RESEARCH, 1983, 11 (05) : 1475 - 1489
  • [3] 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2) IS A LIGAND FOR THE ADIPOCYTE DETERMINATION FACTOR PPAR-GAMMA
    FORMAN, BM
    TONTONOZ, P
    CHEN, J
    BRUN, RP
    SPIEGELMAN, BM
    EVANS, RM
    [J]. CELL, 1995, 83 (05) : 803 - 812
  • [4] Greene M. E., 1995, Gene Expression, V4, P281
  • [5] Expression of peroxisome proliferator-activated receptors in urinary tract of rabbits and humans
    Guan, YF
    Zhang, YH
    Davis, L
    Breyer, MD
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 1997, 273 (06) : F1013 - F1022
  • [6] Expression of peroxisome proliferator-activated receptor γ (PPARγ) in rat aortic smooth muscle cells
    Iijima, K
    Yoshizumi, M
    Ako, J
    Eto, M
    Kim, S
    Hashimoto, M
    Sugimoto, N
    Liang, YQ
    Sudoh, N
    Toba, K
    Ouchi, Y
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1998, 247 (02) : 353 - 356
  • [7] Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus
    Inzucchi, SE
    Maggs, DG
    Spollett, GR
    Page, SL
    Rife, FS
    Walton, V
    Shulman, GI
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1998, 338 (13) : 867 - 872
  • [8] PPAR-γ agonists inhibit production of monocyte inflammatory cytokines
    Jiang, CY
    Ting, AT
    Seed, B
    [J]. NATURE, 1998, 391 (6662) : 82 - 86
  • [9] A PROSTAGLANDIN J(2) METABOLITE BINDS PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA AND PROMOTES ADIPOCYTE DIFFERENTIATION
    KLIEWER, SA
    LENHARD, JM
    WILLSON, TM
    PATEL, I
    MORRIS, DC
    LEHMANN, JM
    [J]. CELL, 1995, 83 (05) : 813 - 819
  • [10] EFFECT OF ALPHA-TOCOPHEROL ON RESTENOSIS AFTER ANGIOPLASTY IN A MODEL OF EXPERIMENTAL ATHEROSCLEROSIS
    LAFONT, AM
    CHAI, YC
    CORNHILL, JF
    WHITLOW, PL
    HOWE, PH
    CHISOLM, GM
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1995, 95 (03) : 1018 - 1025