TY - JOUR
T1 - Vasohibin-2 aggravates development of ascending aortic aneurysms but not abdominal aortic aneurysms nor atherosclerosis in apoe-deficient mice
AU - Otaka, Nozomu
AU - Uchida, Haruhito A.
AU - Okuyama, Michihiro
AU - Hada, Yoshiko
AU - Onishi, Yasuhiro
AU - Kakio, Yuki
AU - Takeuchi, Hidemi
AU - Umebayashi, Ryoko
AU - Tanabe, Katsuyuki
AU - Subramanian, Venkateswaran
AU - Daugherty, Alan
AU - Sato, Yasufumi
AU - Wada, Jun
N1 - Publisher Copyright:
© 2021 Oxford University Press. All rights reserved.
PY - 2021/5/1
Y1 - 2021/5/1
N2 - 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.
AB - 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.
KW - Angiotensin II
KW - Aortic aneurysm
KW - Atherosclerosis
KW - Blood pressure
KW - Hypertension
KW - Vasohibin-2
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U2 - 10.1093/ajh/hpaa181
DO - 10.1093/ajh/hpaa181
M3 - Article
C2 - 33180898
AN - SCOPUS:85107088207
SN - 0895-7061
VL - 34
SP - 467
EP - 475
JO - American Journal of Hypertension
JF - American Journal of Hypertension
IS - 5
ER -