In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 13, No. 8b ( 2009-08-02), p. 2713-2723
Abstract:
This study aims to develop a new animal model of vulnerable plaques and investigate the potential mechanisms of exogenous p53‐induced plaque instability. Forty rabbits underwent aortic balloon injury, were fed a 1% cholesterol diet for 10 weeks and then normal chow for 6 weeks. Rabbits were divided into Ad5‐CMV.p53‐treated group ( n = 16), Ad5‐CMV.lac Z‐treated group ( n = 16) and blank control group ( n = 8). Under the guidance of intravascular ultrasound, a 50‐μl suspension of adenovirus containing p53 or lac Z was injected into the largest plaque of the first two groups, respectively, and these rabbits received pharmacological triggering 2 weeks later. In 76.9% of rabbits with p53 transfection, plaque rupture was found, which was significantly ( P 〈 0.05) higher than that in the Ad5‐CMV.lac Z‐treated plaques (23.1%), or blank controls plaques (0%). Increased apoptotic cells, and subsequently, decreased vascular smooth muscle cells and collagen content, enhanced intima macrophage accumulation, increased C‐reactive protein (CRP) and matrix metalloproteinases staining and high serum levels of high sensitive CRP (hs‐CRP) and monocyte chemoattractant protein‐1 (MCP‐1) were observed in Ad5‐CMV.p53‐treated rabbits. However, a binary logistic regression model revealed that hs‐CRP concentration rather than apoptosis rate played an independent role in plaque rupture with an odds ratio as 1.314 (95% CI: 1.041–1.657, P = 0.021), and there were high positive correlations between inflammatory biomarkers (hs‐CRP or MCP‐1) and apoptosis ( R 2 = 0.761, and R 2 = 0.557, respectively, both P 〈 0.01). Intraplaque injection of p53 gene provides a safe and effective method for inducing plaque vulnerability in rabbits. The destabilizing effect of p53 overexpression is mediated mainly through apoptosis‐enhanced inflammation rather than cell apoptosis itself.
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2009.13.issue-8b
DOI:
10.1111/j.1582-4934.2008.00538.x
Language:
English
Publisher:
Wiley
Publication Date:
2009
detail.hit.zdb_id:
2076114-4
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