目的:以前认为动脉粥样硬化(AS)斑块从内膜开始发展,斑块内血管(VV)增生促进外膜VV(AVV)增生。然而,最近的研究表明,动脉AVV增生先于早期内膜增厚,提示其作为AS的启动因素的可能作用。为了进一步了解这一过程,在这项研究中,我们通过纵向超声成像检查早期AS临床前模型中AAV和VV发展的演变。
方法:建立早期AS模型。进行双重超声扫描和超声造影诊断。采用Pearson相关检验分析AVV增生与VV增生的关系,或AVV增生和内膜中层厚度(IMT)之间。
结果:在0-12周的高脂肪喂养期间,观察区AVV逐渐升高,内膜中膜逐渐增厚;高脂喂养第2周,观察区域显示明显的AVV增殖;在第4周,内膜-中膜变厚;在第12周,观察到早期斑块形成和斑块内VV增殖。AVV增殖与IMT增厚呈强正相关,AVV增殖与血管直径变化率呈强负相关。
结论:这项研究表明,动脉中的AVV增殖比IMT增厚更早,并且与IMT呈正相关。目前,超声诊断AS的指标,比如IMT,斑块内VV,回声属性,都出现在AS的高级阶段。AVV可能是AS斑块早期诊断的创新靶点。
OBJECTIVE: It was previously believed that atherosclerotic (AS) plaque starts to develop from the intima and that intraplaque vasa vasorum (VV) hyperplasia promotes adventitial VV (AVV) hyperplasia. However, recent studies have shown that arterial AVV hyperplasia precedes early intimal thickening, suggesting its possible role as an initiating factor of AS. To provide further insight into this process, in this study, we examine the evolution of AAV and VV development in a preclinical model of early AS with longitudinal ultrasound imaging.
METHODS: Models of early AS were established. Duplex ultrasound scanning and contrast-enhanced ultrasound were performed for diagnosis. Pearson correlation tests were used to analyze the relationships between AVV hyperplasia and VV hyperplasia, or between AVV hyperplasia and intima-media thickness (IMT).
RESULTS: During 0-12 wk of high-fat feeding, AVV gradually increased and intima-media thickened gradually in the observation area; in the 2nd wk of high-fat feeding, the observation area showed obvious AVV proliferation; at the 4th wk, the intima-media membrane became thicker; at the 12th wk, early plaque formation and intraplaque VV proliferation were observed. There was a strong positive correlation between AVV proliferation and IMT thickening and a strong negative correlation between AVV proliferation and the change rate of vessel diameter.
CONCLUSIONS: This study demonstrated that AVV proliferation in the arteries occurred earlier than IMT thickening and was positively correlated with IMT. At present, the indicators of ultrasonic diagnosis of AS, such as IMT, Intraplaque VV, Echo property, all appear in the advanced stage of AS. The AVV may be an innovative diagnostic target for the early stage of AS plaque.