Pathological Study on the Expression of Vasohibins in Peripheral Artery Disease

Pathological Study on the Expression of Vasohibins in Peripheral Artery Disease

Ryutaro Isoda,^1,2 Ichiro Morita,² Atsuhisa Ishida,² Yuka Mikami,¹ Yasumasa Monobe,¹ Yasufumi Sato³ and Takuya Moriya¹

¹Department of Pathology, Kawasaki Medical School, Kurashiki, Okayama, Japan
²Department of Surgery, Kawasaki Medical School General Medical Center, Okayama, Okayama, Japan
³New Industry Creation Hatchery Center, Tohoku University, Sendai, Miyagi, Japan

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.

Keywords —— angiogenesis; detyrosinated alpha-tubulin; peripheral artery disease; smooth muscle cells; vasohibin

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Tohoku J. Exp. Med 2022, 258, 121-128.

Correspondence: Takuya Moriya, M.D., Department of Pathology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.

e-mail: tmoriya@med.kawasaki-m.ac.jp