title: Effect of a new PPAR-gamma agonist, lobeglitazone, on neointimal formation after balloon injury in rats and the development of atherosclerosis.
abstract: OBJECTIVE
  The ligand-activated transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) is a key factor in adipogenesis, insulin sensitivity, and cell cycle regulation. Activated PPARγ might also have anti-inflammatory and antiatherogenic properties. We tested whether lobeglitazone, a new PPARγ agonist, might protect against atherosclerosis.
  
  
  METHODS
  A rat model of balloon injury to the carotid artery, and high-fat, high-cholesterol diet-fed apolipoprotein E gene knockout (ApoE(-/-)) mice were studied.
  
  
  RESULTS
  After the balloon injury, lobeglitazone treatment (0.3 and 0.9 mg/kg) caused a significant decrease in the intima-media ratio compared with control rats (2.2 ± 0.9, 1.8 ± 0.8, vs. 3.3 ± 1.2, P < 0.01). Consistent with this, in ApoE(-/-) mice fed a high-fat diet, lobeglitazone treatment (1, 3, and 10 mg/kg) for 8 weeks reduced atherosclerotic lesion sizes in the aorta compared with the control mice in a dose-dependent manner. Treatment of vascular smooth muscle cells with lobeglitazone inhibited proliferation and migration and blocked the cell cycle G0/G1 to S phase progression dose-dependently. In response to lobeglitazone, tumor necrosis factor alpha (TNFα)-induced monocyte-endothelial cell adhesion was decreased by downregulating the levels of adhesion molecules. TNFα-induced nuclear factor kappa-B (NF-κB) p65 translocation into the nucleus was also blocked in endothelial cells. Insulin resistance was decreased by lobeglitazone treatment. Circulating levels of high sensitivity C-reactive protein and monocyte chemoattractant protein-1 were decreased while adiponectin levels were increased by lobeglitazone in the high-fat diet-fed ApoE(-/-) mice.
  
  
  CONCLUSIONS
  Lobeglitazone has antiatherosclerotic properties and has potential for treating patients with diabetes and cardiovascular risk.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam, 463-070, South Korea; Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, South Korea.
authors.forename: Soo
authors.initials: S
authors.lastname: Lim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam, 463-070, South Korea; Biomedical Research Institute, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam, 463-070, South Korea.
authors.forename: Kuy-Sook
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam, 463-070, South Korea; Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, South Korea.
authors.forename: Jie Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, South Korea.
authors.forename: Ho Seon
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam, 463-070, South Korea; Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, South Korea.
authors.forename: Kyoung Min
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam, 463-070, South Korea; Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, South Korea.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Moon
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam, 463-070, South Korea; Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, South Korea.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, South Korea; Biomedical Research Institute, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam, 463-070, South Korea.
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
authors.affiliation: Biomedical Research Institute, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam, 463-070, South Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 110-744, South Korea; Division of Endocrinology, Metabolism and Diabetes, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA, 02215, USA.
authors.forename: Young Bum
authors.initials: YB
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam, 463-070, South Korea; Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, South Korea. Electronic address: janghak@snu.ac.kr.
authors.forename: Hak Chul
authors.initials: HC
authors.lastname: Jang
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000517:prevention & control*; D002097:C-Reactive Protein / Q000378:metabolism; D002339:Carotid Arteries / Q000473:pathology; D002448:Cell Adhesion; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D059305:Diet, High-Fat; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058426:Neointima / Q000188:drug therapy*; D047495:PPAR gamma / Q000819:agonists*; D058226:Plaque, Atherosclerotic / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D045162:Thiazolidinediones / Q000627:therapeutic use*; D051996:Transcription Factor RelA / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D047495:PPAR gamma; D011743:Pyrimidines; C498144:Rela protein, mouse; C498145:Rela protein, rat; D045162:Thiazolidinediones; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D002784:Cholesterol; C546215:lobeglitazone
keywords: Atherosclerosis; Endothelium; PPARγ; Vascular smooth muscle cells