Key result
Local delivery of recombinant p53 adenovirus induced plaque rupture in 81.1% of rabbits compared to 26.3% with control vector (P<0.001), with ultrasound and biochemical markers predicting rupture.
Absolute Event Rate: 81.1% vs 26.3%
p-value: p=<0.001
In a rabbit model, localized p53 overexpression induces plaque rupture, which can be predicted by a combination of high-frequency ultrasound parameters and serum inflammatory markers.
p53 overexpression induces rupture in rabbits; extends experimental models but leaves human plaque vulnerability open.
Atherosclerotic plaque rupture and thrombosis are the main causes of acute coronary syndrome. In the present study, we investigated whether ultrasound imaging and inflammatory parameters are predictive of plaque rupture in a newly established animal model. We developed a rabbit model for plaque rupture by locally delivering recombinant p53 adenovirus to plaques in rabbits fed a high-cholesterol diet for 10 wk, and plaque rupture was triggered using Chinese Russell's viper venom and histamine. We found that 81.1% of rabbits transfected with p53 (n = 37) had the ruptured plaques, which was significantly higher than results in rabbits transfected with the control vector (26.3%, n = 38; P < 0.001). Among measured biomarkers, high-sensitive C-reactive protein, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 were significantly different between rabbits with and without ruptured plaques. Using high-frequency duplex and intravascular ultrasound imaging techniques, we obtained a list of parameters. With the multivariate logistic regression model, we identified that plaque eccentric index, plaque area, high-sensitive C-reactive protein, and corrected integrated backscatter intensity were significant predictors of plaque rupture, with odds ratios of 7.056 [95% confidence interval (CI): 1.958, approximately 25.430], 1.942 (95% CI: 1.058, approximately 3.564), 1.025 (95% CI: 1.007, approximately 1.043), and 0.856 (95% CI: 0.775, approximately 0.946), respectively. Localized p53 overexpression technique induces plaque rupture, and the combined measurement of ultrasound and biochemical markers is a valuable tool in predicting plaque rupture.
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Chen et al. (2007) studied Atherosclerotic plaque rupture (n=75). Recombinant p53 adenovirus vs. Control vector was evaluated on Plaque rupture (p=<0.001). Local delivery of recombinant p53 adenovirus induced plaque rupture in 81.1% of rabbits compared to 26.3% with control vector (P<0.001), with ultrasound and biochemical markers predicting rupture.
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