Arterial Adventitial Vasa Vasorum Hyperplasia involved in Atherosclerotic Plaque Formation in a Rabbit Model

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. Conclusion: 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.