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Background This study was to explore the influencing factors of atherosclerotic plaque formation and stability in patients with asymptomatic carotid atherosclerotic plaques, so as to identify the vulnerable plaques at early stage, and then find high-risk group of cardio-cerebrovascular events for early clinical intervention to reduce related mortality and disability. Methods A total of 302 enrolled patients with asymptomatic carotid atherosclerotic plaques were divided into 3 groups based on the results of carotid artery color Doppler ultrasound: atherosclerotic unstable plaque (UP) group, atherosclerotic stable plaque (SP) group, and control group without plaques. Serum markers were measured by ELISA. χ2 test, t test, Pearson correlation analysis, and Logistic multivariate regression analysis were used in the analysis, and P < 0.05 was considered statistically significant. Results It revealed that high MMP-9, LOX-1and YKL-40 were independent risk factors for unstable plaque formation. The area under the curve (AUC) of serum markers combined with MMP-9, LOX-1 and YKL-40 was 0.850, with sensitivity 87.67%, specificity 81.13%, and diagnostic accuracy 84.92%, which was significantly better than the individual diagnostic efficacy of other three factors. The accuracy rate of Crouse Plaque Score (CPS) in the diagnosis of vulnerable plaques was 61.90%, the 10-year ICVD diagnosis accuracy rate was 56.75%, and the diagnostic accuracy of serum markers was significantly better than CPS and 10-year ICVD. Conclusion Noninvasive cervical color Doppler ultrasound combined with serum markers MMP-9, LOX-1 and YKL-40 have significant early recognition effect on asymptomatic carotid vulnerable plaque patients.

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We previously showed that anthraquinones (including rhein, emodin, aloe-emodin, chrysophanol and physcion) were inhibitors of human organic anion transporter 1 (hOAT1) and hOAT3, causing transporter-mediated drug-drug interactions in rats. In this study, the time-dependent inhibition (TDI) of hOAT1 and hOAT3 by anthraquinones was investigated. Madin-Darby canine kidney (MDCK)-hOAT1, HEK293-hOAT3 and their parental cells were used. Preincubation with chrysophanol or physcion for 30 min significantly increased the inhibition of hOAT1, but preincubation with rhein, emodin, aloe-emodin or probenecid had no effect on hOAT1 activity. By contrast, preincubation of hOAT3 with emodin, aloe-emodin, chrysophanol or physcion for 30 min significantly increased its inhibition, but preincubation with rhein or probenecid had no effect on activity. As the incubating time lengthened, from 0 to 60 min, both the inhibition of hOAT1 by chrysophanol and physcion and the inhibition of hOAT3 by emodin, aloe-emodin, chrysophanol and physcion were observed to increase in a time-dependent manner. In conclusion, our results suggest that some anthraquinones contribute to the TDI of hOAT1 and hOAT3. An inhibition study without the preincubation procedure may underestimate the inhibitory potential of anthraquinones against hOAT1 and hOAT3. The underlying mechanisms of TDI of hOAT1 and hOAT3 need to be further investigated. Key words organic anion transporter; anthraquinone; timedependent inhibitionIn CYP450 enzyme-mediated metabolism, time-dependent inhibition (TDI) has attracted significant attention. TDI of CYP450 enzymes refers to a change in the inhibitory potency during an in vitro incubation or dosing period in vivo. 1)However, does drug transporter-based TDI exist? Amundsen et al.2) reported that inhibition of organic anion transporting polypeptide 1B1 (OATP1B1) by cyclosporine A occurred in a time-dependent manner. Preincubation of OATP1B1 with cyclosporine A increased the inhibition of this protein; however, the underlying mechanism was not described in that report. Other researchers found that preincubation of OATP2B1 with apple juice or orange juice increased their inhibition effect.3)In general, there are very few articles that report on drug transporter-based TDI.In our previous study, we found that anthraquinones (rhein, emodin, aloe-emodin, chysophanol or physcion) inhibited human organic anion transporter 1 (hOAT1) and hOAT3. 4)Anthraquinones were coincubated with substrates of hOAT1 or hOAT3 in that study. However, we observed that preincubation of hOAT1 and hOAT3 with some of the anthraquinones increased hOAT1 and hOAT3 inhibition. Currently, TDI of the OATs family has not been studied. Therefore, in this study, the inhibitory effect of preincubation anthraquinones with hOAT1 and hOAT3 was investigated. The results provide evidence for the complex inhibitory mechanisms of drug transporters.