Peroxisome proliferator-activated receptor gamma ligand pioglitazone alters neointimal composition in a balloon-denuded and radiated hypercholesterolemic rabbit.
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.
Pakala
Rajbabu
R
Cardiovascular Research Institute, Washington Hospital Center, Washington, DC, USA.
Dilcher
Christian
C
Baffour
Richard
R
Hellinga
David
D
Seabron
Rufus
R
Joner
Michael
M
Kolodgie
Frank
F
Virmani
Renu
R
Waksman
Ron
R
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
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