Pioglitazone attenuates neointimal thickening via suppression of the early inflammatory response in a porcine coronary after stenting.
Enhanced early inflammatory response accelerated the neointimal hyperplasia after vascular injury. Pioglitazone has antiatherogenic property through the inhibition of inflammation. Thus, we hypothesized that pioglitazone might inhibit the early inflammatory response, resulting in reduced neointimal hyperplasia in porcine coronary stenting model. Pioglitazone (5mg/kg/day) or placebo was administered orally to 10 pigs (20 coronaries) in each, from 7 days before stenting until the time of euthanasia at 3 or 28 days after stenting. The coronary artery of the pigs was injured with an oversized bare metal stent. Early inflammatory cell infiltration on the vessel surface was evaluated by scanning electron microscopy and was significantly suppressed in pioglitazone-treated group comparing with the control (% of site occurring greater infiltration: 40.8% versus 60.9%; P=0.002). Immunohistochemistry revealed that activated NF-kappaB and MCP-1 expression in the vessel was of significantly less in the pioglitazone-treated group. On day 28, morphometric assessment of stent-section showed significant reduction of neointimal thickness in the pioglitazone-treated group comparing with the control (neointimal thickness: 386.5+/-78.2mm versus 591.7+/-238.6mm; P=0.0051), whereas there was no difference in the injury score between two groups. Pioglitazone inhibited neointimal hyperplasia after stenting through a reduction of early inflammatory response.
Kasai
Takatoshi
T
Department of Cardiology, Juntendo University, School of Medicine, 2-1-1 Hongo, Tokyo, Japan.
Miyauchi
Katsumi
K
Yokoyama
Takayuki
T
Kajimoto
Kan
K
Sumiyoshi
Katsuhiko
K
Kubota
Naozumi
N
Ikeda
Eiji
E
Daida
Hiroyuki
H
D000818:Animals; D018932:Chemokine CCL2 / Q000187:drug effects; D023903:Coronary Restenosis / Q000276:immunology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D008854:Microscopy, Electron; D016328:NF-kappa B / Q000187:drug effects; D000077205:Pioglitazone; D015607:Stents; D034421:Sus scrofa; D045162:Thiazolidinediones / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects*
D018932:Chemokine CCL2; D007004:Hypoglycemic Agents; D016328:NF-kappa B; D045162:Thiazolidinediones; D000077205:Pioglitazone