Decreased PPAR-γ expression after internal carotid artery stenting is associated with vascular lesions induced by smooth muscle cell proliferation and systemic inflammation in a minipig model

Hongchen Wu; Yuanrui Yang; Bo Zheng; Kangning Chen

Decreased PPAR-γ expression after internal carotid artery stenting is associated with vascular lesions induced by smooth muscle cell proliferation and systemic inflammation in a minipig model

Int J Clin Exp Pathol. 2017 Jul 1;10(7):7375-7383. eCollection 2017.

Authors

Hongchen Wu¹, Yuanrui Yang^{1

2}, Bo Zheng¹, Kangning Chen¹

Affiliations

¹ Department of Neurology, Southwest Hospital, Third Military Medical University Chongqing, China.
² Department of Geriatrics, People's Liberation Army General Hospital of Chengdu Military Region Chengdu, Sichuan Province, China.

PMID: 31966579
PMCID: PMC6965304

Abstract

Vascular restenosis after stenting is known to be largely mediated by proliferation of vascular smooth muscle cells. Recently, peroxisome proliferator-activated receptor gamma (PPAR-γ) has been implicated as a regulator of cellular inflammatory responses, and the PPAR-γ agonist rosiglitazone (ROSI) has been shown to attenuate atherosclerosis formation. However, whether ROSI can inhibit neointimal formation by regulating the inflammatory response and inhibiting vascular smooth muscle hyperplasia after stenting-induced injury remains to be clarified. Accordingly, in this study, 10 minipigs were randomly divided into two groups: the stenting group (n = 5) and the ROSI group (n = 5). Morphometric analysis was conducted for the stented arteries. The protein expressions of PPAR-γ and smooth muscle 22-alpha (SM22α) were analyzed by immunohistochemistry and western blotting, and the serum interferon-γ and interleukin-10 levels were measured by enzyme-linked immunosorbent assay. Three months after implantation, morphometric analysis revealed that administration of ROSI (0.5 mg/kg/d, continuous administration for 90 days) resulted in significant reductions of luminal stenosis, the neointimal area, and neointimal thickness, as compared to the stenting groups. The expression of PPAR-γ and the PPAR-γ/SM22α ratio in the ROSI group were higher than in the stenting group. Furthermore, the serum interferon-γ and interleukin-10 levels were found to be increased and to reach peak levels at 4 h and 7 days after stenting, respectively, after which both declined. However, ROSI treatment resulted in decreased interferon-γ and increased interleukin-10 levels after stenting. In both groups, the cytokine levels returned to the baseline levels on day 56 after stenting. Taken together, these results suggest that ROSI can reduce neointimal formation after stenting by inhibiting the local and systemic inflammatory responses as well as vascular smooth muscle hyperplasia.

Keywords: Stent implantation; interferon-γ; interleukin-10; peroxisome proliferator-activated receptor-γ.