Vasohibin-2 aggravates development of ascending aortic aneurysms but not abdominal aortic aneurysms nor atherosclerosis in apoe-deficient mice

Nozomu Otaka, Haruhito A. Uchida, Michihiro Okuyama, Yoshiko Hada, Yasuhiro Onishi, Yuki Kakio, Hidemi Takeuchi, Ryoko Umebayashi, Katsuyuki Tanabe, Venkateswaran Subramanian, Alan Daugherty, Yasufumi Sato, Jun Wada

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

BACKGROUND Vasohibin-2 (VASH2) has been isolated as a homologue of vasohibin-1 (VASH1) that promotes angiogenesis counteracting with VASH1. Chronic angiotensin II (AngII) infusion promotes both ascending and abdominal aortic aneurysms (AAs) in mice. The present study aimed to investigate whether exogenous VASH2 influenced AngII-induced vascular pathology in apolipoprotein E-deficient (ApoE-/-) mice. METHODS Male, ApoE-/- mice (9-14 weeks old) were injected with Ad LacZ or Ad VASH2. After a week, saline or AngII (1,000 ng/kg/minute) was infused into the mice subcutaneously via mini-osmotic pumps for 3 weeks. Consequently, all these mice were divided into 4 groups: Saline + LacZ (n = 5), saline + VASH2 (n = 5), AngII + LacZ (n = 18), and AngII + VASH2 (n = 17). RESULTS Exogenous VASH2 had no significant effect on ex vivo maximal diameters of abdominal aortas (AngII + LacZ: 1.67 ± 0.17 mm, AngII + VASH2: 1.52 ± 0.16 mm, n.s.) or elastin fragmentation and accumulation of inflammatory cells. Conversely, exogenous VASH2 significantly increased intima areas of aortic arches (AngII + LacZ: 16.6 ± 0.27 mm2, AngII + VASH2: 18.6 ± 0.64 mm2, P = 0.006). VASH2 effect of AngII-induced ascending AAs was associated with increased cleaved caspase-3 abundance. AngII-induced atherosclerosis was not altered by VASH2. CONCLUSIONS The present study demonstrated that augmented VASH2 expression had no effect of AngII-induced abdominal AAs or atherosclerosis, while increasing dilation in the ascending aorta.

Original languageEnglish
Pages (from-to)467-475
Number of pages9
JournalAmerican Journal of Hypertension
Volume34
Issue number5
DOIs
Publication statusPublished - May 1 2021

Keywords

  • Angiotensin II
  • Aortic aneurysm
  • Atherosclerosis
  • Blood pressure
  • Hypertension
  • Vasohibin-2

ASJC Scopus subject areas

  • Internal Medicine

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