title: Peroxisome proliferator-activated receptor gamma ligand pioglitazone alters neointimal composition in a balloon-denuded and radiated hypercholesterolemic rabbit.
abstract: Peroxisome proliferator-activated receptor (PPAR)-gamma activation suppresses inflammatory response, monocyte recruitment, and vascular cell proliferation. Because inflammation, deregulated growth, and migration of monocytes and vascular smooth muscle cells (VSMC) play important roles in the development of neointima, we tested the effect of pioglitazone, a high-affinity ligand, for PPAR-gamma on neointima formation in the iliac arteries of a balloon-denuded and radiated hypercholesterolemic rabbit. Rabbits were fed a 1.0% cholesterol diet for 7 days followed by denudation of endothelial layer and continued on a 0.15% cholesterol diet. On day 32, animals were divided into 2 groups. One group received a 0.15% cholesterol diet (n = 7) and the other group received a 0.15% cholesterol diet supplemented with 400 mg of pioglitazone per kilogram. On day 35, the balloon-denuded area was radiated. Four weeks after radiation, animals were sacrificed and arterial segments were processed for morphometry and immunohistochemistry. Data analysis showed that the pioglitazone group had smaller neointima (0.85 +/- 0.36 vs. 1.41 +/- 0.56, P < 0.05), with more cells positive for VSMC (23.07 +/- 6.16 vs. 18.33 +/- 5.19, P = 0.04), less for monocytes (16.01 +/- 5.33 vs. 21.29 +/- 4.33, P < 0.05), and fewer cells expressing metalloproteinase (MMP)-1 and MMP-9 (3.69 +/- 0.47 vs. 4.82 +/- 0.93, P < 0.05 and 3.24 +/- 0.71 vs. 4.29 +/- 0.74, P < 0.05, respectively). Pioglitazone reduced neointimal area and modified its composition in a balloon-denuded and radiated hypercholesterolemic rabbit model.
authors.affiliation: Cardiovascular Research Institute, Washington Hospital Center, Washington, DC, USA.
authors.forename: Rajbabu
authors.initials: R
authors.lastname: Pakala
authors.forename: Christian
authors.initials: C
authors.lastname: Dilcher
authors.forename: Richard
authors.initials: R
authors.lastname: Baffour
authors.forename: David
authors.initials: D
authors.lastname: Hellinga
authors.forename: Rufus
authors.initials: R
authors.lastname: Seabron
authors.forename: Michael
authors.initials: M
authors.lastname: Joner
authors.forename: Frank
authors.initials: F
authors.lastname: Kolodgie
authors.forename: Renu
authors.initials: R
authors.lastname: Virmani
authors.forename: Ron
authors.initials: R
authors.lastname: Waksman
mesh_terms: D000199:Actins / Q000032:analysis; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002404:Catheterization; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007150:Immunohistochemistry; D008264:Macrophages / Q000737:chemistry / Q000187:drug effects; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000032:analysis; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D011817:Rabbits; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017539:Tunica Intima / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D017540:Tunica Media / Q000737:chemistry / Q000187:drug effects / Q000473:pathology
chemical_list: D000199:Actins; D002791:Cholesterol, Dietary; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D000077205:Pioglitazone