Department of Pathology, Kawasaki Medical School.
Department of Surgery, Kawasaki Medical School General Medical Center.
Tohoku J Exp Med. 2022 Sep 14;258(2):121-128. doi: 10.1620/tjem.2022.J063. Epub 2022 Aug 4.
Vasohibin-2 (VASH2) is a gene that promotes local angiogenesis. The tubulin carboxypeptidase activity of vasohibin causes detyrosination of alpha-tubulin and may play an important role in the regulation of various phenomena. Pathological and therapeutic angiogenesis are involved in atherosclerotic lesions. This study aimed to investigate whether the expression of VASH2 is associated with peripheral artery disease (PAD) in relation to angiogenesis, tubulin detyrosination, and severity of atherosclerotic lesions. An analysis of femoral and tibial arteries obtained from 86 patients with PAD or abdominal aortic aneurysm (AAA) was performed. The expressions of cluster of differentiation 31, VASH1, VASH2, and detyrosinated alpha-tubulin (DT-tubulin) were examined by immunohistochemistry, and their association with PAD was analyzed. The counts of VASH2 in the tunica media and adventitia in the tibial artery were significantly higher than those in the femoral artery in the PAD (P = 0.005 and P = 0.008, respectively) and AAA (P = 0.002 and P < 0.001, respectively) groups. In the tunica media and adventitia, VASH2 was significantly correlated with DT-tubulin. There was no significant difference in the expression of VASH2 and DT-tubulin in medial smooth muscle cells (McNemar test, P > 0.999). This study revealed the possible involvements of VASH2 in atherosclerosis by two methods-one maybe related to the progression of atherosclerosis by inducing angiogenesis and the second may be related to the decrease in arterial elasticity by increasing DT-tubulin in medial smooth muscle cells.
血管生成素 2（VASH2）是一种促进局部血管生成的基因。血管生成素的微管羧肽酶活性导致α-微管脱酪氨酸化，可能在调节各种现象中发挥重要作用。病理性和治疗性血管生成参与动脉粥样硬化病变。本研究旨在探讨 VASH2 的表达是否与血管生成、微管脱酪氨酸化和动脉粥样硬化病变严重程度有关，从而与周围动脉疾病（PAD）相关。对 86 例 PAD 或腹主动脉瘤（AAA）患者的股动脉和胫动脉进行了分析。采用免疫组织化学法检测 CD31、VASH1、VASH2 和脱酪氨酸化α-微管（DT-tubulin）的表达，并分析其与 PAD 的关系。胫动脉中膜和外膜中 VASH2 的计数在 PAD（P=0.005 和 P=0.008）和 AAA（P=0.002 和 P<0.001）组中均明显高于股动脉。中膜和外膜中 VASH2 与 DT-tubulin 呈显著相关。中膜平滑肌细胞中 VASH2 和 DT-tubulin 的表达无显著差异（McNemar 检验，P>0.999）。本研究通过两种方法揭示了 VASH2 可能参与动脉粥样硬化的机制-一种可能通过诱导血管生成而与动脉粥样硬化的进展有关，另一种可能通过增加中膜平滑肌细胞中的 DT-tubulin 而与动脉弹性降低有关。
