(Circulation. 2000;101:1311.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Expression and Function of PPAR
in Rat and Human Vascular Smooth Muscle Cells
From the Department of Medicine (R.E.L., S.G., X.-P.X., S.J., Y.K., L.D., W.P.M., W.A.H.); the Division of Endocrinology, Diabetes, and Hypertension (R.E.L., S.G., X.-P.X., Y.K., W.P.M., W.A.H.); the Division of Cardiology (S.J., L.D.); and the Department of Pathology and Laboratory Medicine (M.C.F.), University of California at Los Angeles School of Medicine.
Correspondence to Ronald E. Law, PhD, UCLA, Warren Hall, Second Floor, Suite 24-130, 900 Veteran Ave, Los Angeles, CA 90095.
Background—Peroxisome
proliferator–activated receptor-
(PPAR) 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 PPAR1. Three PPAR ligands, the TZDs TRO and
rosiglitazone and the prostanoid
15-deoxy-
12,14-prostaglandin J2 (15d-PGJ2),
all inhibited VSMC proliferation and migration. PPAR 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 expressed in
VSMCs inhibits their proliferation and migration, potentially limiting
restenosis and atherosclerosis. These receptors
are upregulated during vascular injury.
Key Words: atherosclerosis • restenosis • growth substances • migration • thiazolidinediones
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J. Zhang, M. Fu, X. Zhu, Y. Xiao, Y. Mou, H. Zheng, M. A. Akinbami, Q. Wang, and Y. E. Chen Peroxisome Proliferator-activated Receptor delta Is Up-regulated during Vascular Lesion Formation and Promotes Post-confluent Cell Proliferation in Vascular Smooth Muscle Cells J. Biol. Chem., March 22, 2002; 277(13): 11505 - 11512. [Abstract] [Full Text] [PDF]
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N. Frey and E. N. Olson Modulating Cardiac Hypertrophy by Manipulating Myocardial Lipid Metabolism? Circulation, March 12, 2002; 105(10): 1152 - 1154. [Full Text] [PDF]
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 B. Molavi, N. Rasouli, and J. L. Mehta Peroxisome Proliferator-Activated Receptor Ligands as Antiatherogenic Agents: Panacea or Another Pandora's Box? Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2002; 7(1): 1 - 8. [Abstract] [PDF]
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S. Arima, K. Kohagura, K. Takeuchi, Y. Taniyama, A. Sugawara, Y. Ikeda, M. Abe, K. Omata, and S. Ito Biphasic Vasodilator Action of Troglitazone on the Renal Microcirculation J. Am. Soc. Nephrol., February 1, 2002; 13(2): 342 - 349. [Abstract] [Full Text] [PDF]
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W. A. Hsueh and R. E. Law PPAR{gamma} and Atherosclerosis: Effects on Cell Growth and Movement Arterioscler Thromb Vasc Biol, December 1, 2001; 21(12): 1891 - 1895. [Abstract] [Full Text] [PDF]
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M. Fu, J. Zhang, X. Zhu, D. E. Myles, T. M. Willson, X. Liu, and Y. E. Chen Peroxisome Proliferator-activated Receptor gamma Inhibits Transforming Growth Factor beta -induced Connective Tissue Growth Factor Expression in Human Aortic Smooth Muscle Cells by Interfering with Smad3 J. Biol. Chem., November 30, 2001; 276(49): 45888 - 45894. [Abstract] [Full Text] [PDF]
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D. P. Kelly The Pleiotropic Nature of the Vascular PPAR Gene Regulatory Pathway Circ. Res., November 23, 2001; 89(11): 935 - 937. [Full Text] [PDF]
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 L. BENAYOUN, S. LETUVE, A. DRUILHE, J. BOCZKOWSKI, M.-C. DOMBRET, P. MECHIGHEL, J. MEGRET, G. LESECHE, M. AUBIER, and M. PRETOLANI Regulation of Peroxisome Proliferator-activated Receptor gamma Expression in Human Asthmatic Airways . Relationship with Proliferation, Apoptosis, and Airway Remodeling Am. J. Respir. Crit. Care Med., October 15, 2001; 164(8): 1487 - 1494. [Abstract] [Full Text] [PDF]
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 X. Xu, M. Otsuki, H. Saito, S. Sumitani, H. Yamamoto, N. Asanuma, H. Kouhara, and S. Kasayama PPAR{alpha} and GR Differentially Down-Regulate the Expression of Nuclear Factor-{kappa}B-Responsive Genes in Vascular Endothelial Cells Endocrinology, August 1, 2001; 142(8): 3332 - 3339. [Abstract] [Full Text] [PDF]
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 C. J. Hupfeld and R. H. Weiss TZDs inhibit vascular smooth muscle cell growth independently of the cyclin kinase inhibitors p21 and p27 Am J Physiol Endocrinol Metab, August 1, 2001; 281(2): E207 - E216. [Abstract] [Full Text] [PDF]
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Q. N. Diep and E. L. Schiffrin Increased Expression of Peroxisome Proliferator-Activated Receptor-{alpha} and -{gamma} in Blood Vessels of Spontaneously Hypertensive Rats Hypertension, August 1, 2001; 38(2): 249 - 254. [Abstract] [Full Text] [PDF]
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 T. Murata, Y. Hata, T. Ishibashi, S. Kim, W. A. Hsueh, R. E. Law, and D. R. Hinton Response of Experimental Retinal Neovascularization to Thiazolidinediones Arch Ophthalmol, May 1, 2001; 119(5): 709 - 717. [Abstract] [Full Text] [PDF]
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A. R. Collins, W. P. Meehan, U. Kintscher, S. Jackson, S. Wakino, G. Noh, W. Palinski, W. A. Hsueh, and R. E. Law Troglitazone Inhibits Formation of Early Atherosclerotic Lesions in Diabetic and Nondiabetic Low Density Lipoprotein Receptor-Deficient Mice Arterioscler Thromb Vasc Biol, March 1, 2001; 21(3): 365 - 371. [Abstract] [Full Text] [PDF]
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C. S. Elangbam, R. D. Tyler, and R. M. Lightfoot Peroxisome Proliferator-activated Receptors in Atherosclerosis and Inflammation--An Update Toxicol Pathol, February 1, 2001; 29(2): 224 - 231. [Abstract] [PDF]
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W. A. Hsueh, S. Jackson, and R. E. Law Control of Vascular Cell Proliferation and Migration by PPAR-{gamma}: A new approach to the macrovascular complications of diabetes Diabetes Care, February 1, 2001; 24(2): 392 - 397. [Abstract] [Full Text]
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S. B. Nicholas, Y. Kawano, S. Wakino, A. R. Collins, and W. A. Hsueh Expression and Function of Peroxisome Proliferator-Activated Receptor-{{gamma}} in Mesangial Cells Hypertension, February 1, 2001; 37(2): 722 - 727. [Abstract] [Full Text] [PDF]
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 A. A. Parulkar, M. L. Pendergrass, R. Granda-Ayala, T. R. Lee, and V. A. Fonseca Nonhypoglycemic Effects of Thiazolidinediones Ann Intern Med, January 2, 2001; 134(1): 61 - 71. [Abstract] [Full Text] [PDF]
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 T. Murata, S. He, M. Hangai, T. Ishibashi, X.-P. Xi, S. Kim, W. A. Hsueh, S. J. Ryan, R. E. Law, and D. R. Hinton Peroxisome Proliferator-Activated Receptor-{gamma} Ligands Inhibit Choroidal Neovascularization Invest. Ophthalmol. Vis. Sci., July 1, 2000; 41(8): 2309 - 2317. [Abstract] [Full Text]
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K. Takeda, T. Ichiki, T. Tokunou, N. Iino, and A. Takeshita 15-Deoxy-Delta 12,14-prostaglandin J2 and Thiazolidinediones Activate the MEK/ERK Pathway through Phosphatidylinositol 3-Kinase in Vascular Smooth Muscle Cells J. Biol. Chem., December 21, 2001; 276(52): 48950 - 48955. [Abstract] [Full Text] [PDF]
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S. Wakino, U. Kintscher, S. Kim, F. Yin, W. A. Hsueh, and R. E. Law Peroxisome Proliferator-activated Receptor gamma Ligands Inhibit Retinoblastoma Phosphorylation and G1right-arrow S Transition in Vascular Smooth Muscle Cells J. Biol. Chem., July 14, 2000; 275(29): 22435 - 22441. [Abstract] [Full Text] [PDF]
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M. Fu, X. Zhu, Q. Wang, J. Zhang, Q. Song, H. Zheng, W. Ogawa, J. Du, and Y. E. Chen Platelet-Derived Growth Factor Promotes the Expression of Peroxisome Proliferator-Activated Receptor {gamma} in Vascular Smooth Muscle Cells by a Phosphatidylinositol 3-Kinase/Akt Signaling Pathway Circ. Res., November 23, 2001; 89(11): 1058 - 1064. [Abstract] [Full Text] [PDF]
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M. Asakawa, H. Takano, T. Nagai, H. Uozumi, H. Hasegawa, N. Kubota, T. Saito, Y. Masuda, T. Kadowaki, and I. Komuro Peroxisome Proliferator-Activated Receptor {gamma} Plays a Critical Role in Inhibition of Cardiac Hypertrophy In Vitro and In Vivo Circulation, March 12, 2002; 105(10): 1240 - 1246. [Abstract] [Full Text] [PDF]
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