Prediction of atherosclerotic plaque ruptures with high-frequency ultrasound imaging and serum inflammatory markers

Abstract

. Prediction of atherosclerotic plaque ruptures with high-frequency ultrasound imaging and serum inflammatory markers. Am J Physiol Heart Circ Physiol 293: H2836-H2844, 2007. First published August 17, 2007; doi:10.1152/ajpheart.00472.2007.-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 ϭ 37) had the ruptured plaques, which was significantly higher than results in rabbits transfected with the control vector (26.3%, n ϭ 38; P Ͻ 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, ϳ25.430], 1.942 (95% CI: 1.058, ϳ3.564), 1.025 (95% CI: 1.007, ϳ1.043), and 0.856 (95% CI: 0.775, ϳ0.946), 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. atherosclerosis; vulnerable plaque; p53; biomarkers ATHEROSCLEROTIC PLAQUE RUPTURE is the major cause of acute coronary syndrome (ACS) (4, 9).A plaque with a thin cap, a large lipid core, and abundant activated macrophages has been generally regarded as unstable and vulnerable to rupture. Although early detection or prevention would be the only way to reduce the risk of this catastrophic life-threatening event, there is frustratingly little progress in either. Lack of suitable animal models has considerably hampered the research progress in understanding molecular events occurring in the development of plaque rupture. It remains unclear what morphological and biochemical features will best predict plaque rupture and which in vivo diagnostic technologies would reliably predict the pathological and clinical courses of an unstable plaque. Currently, most factors found to be associated with plaque rupture and ensuing thrombosis in ACS are derived from cross-sectional retrospective rather than prospective studies (3,22,29).Recently, a variety of imaging techniques, including highfrequency duplex ultrasound, intravascular ultrasound (IVUS), IVUS elastography, coronary ...

Independent Roles of Monocyte Chemoattractant Protein-1, Regulated on Activation, Normal T-Cell Expressed and Secreted and Fractalkine in the Vulnerability of Coronary Atherosclerotic Plaques

“…Coronary plaque composition was assessed visually according to plaque echogenicity. 17, 18 Plaque rupture was defined as a plaque containing a cavity that communicated with the lumen and had an overlying residual fibrous cap fragment or was wedged by newly-formed thrombus, no matter whether plaque rupture occurred in culprit or non-culprit lesions. 19 The IVUS images were reviewed by 2 independent observers and the final consensus values were used for data analysis.…”

Arginase I Attenuates Inflammatory Cytokine Secretion Induced by Lipopolysaccharide in Vascular Smooth Muscle Cells

“…At the end of 12 weeks, physiological saline, Arg I lentivirus, pGC FU-green fluorescent protein-lentivirus (LV), rabbit ARGI-RNAi lentivirus (sequences: forward, 5Ј-GGUGGAUGCUCAUACUGAUTT-3Ј, reverse, 5Ј-AUCAGUAU-GAGCAUCCACCTT-3Ј; forward, 5Ј-GUCCUACAGUAUUGAG-AAATT-3Ј, reverse, 5Ј-UUUCUCAAUACUGUAGGACTT-3Ј), and pGC FU-RNAi-NC-LV were locally delivered to plaques as described. 18 At the end of 16 weeks, all rabbits were anesthetized and killed for pathological studies. All animal care and experimental protocols complied with the animal management rules of the Ministry of Health of the People's Republic of China (document no.…”

Probucol Attenuates Inflammation and Increases Stability of Vulnerable Atherosclerotic Plaques in Rabbits

“…55, 2001), and the study was approved by the Animal Care Committee of Shandong University. The rabbit vulnerability plaque model was established as we previously described (Chen et al 2007). Forty-five male New Zealand White rabbits (2.0 to 2.5 kg) were fed with an atherogenic diet containing 1% cholesterol for 24 weeks after balloon-induced aortic endothelial injury as described.…”

“…To induce vulnerable plaques, at the end of week 22, all animals were injected with adenoviral vector containing recombinant p53 as described previously (Chen et al 2007). In brief, with the rabbits under sufficient anesthesia, a midlineincision along the abdomen was made and the abdominal aorta was exposed.…”

“…Since most preclinical probucol treatments have been done in the early stage of atherosclerosis, the exact effect of probucol on the final steps of atherosclerosis, namely plaque destabilization and eventually plaque rupture, and the underlying mechanisms have not been well explored. The present study was performed to evaluate the effect of probucol on the atherosclerotic plaque stability and its possible mechanism in a rabbit model of vulnerable atherosclerotic plaques we previously verified (Chen et al 2007;Zhang et al 2008;Zhong et al 2008). Since recent clinical trials demonstrated a better outcome in patients with ACS under intensive statin treatment (Grundy et al 2004;Chan et al 2007), a high-dose of simvastatin was chosen as a positive control therapy to compare with probucol.…”