Vasohibin-2 Aggravates Development of Ascending Aortic Aneurysms but not Abdominal Aortic Aneurysms nor Atherosclerosis in ApoE-Deficient Mice.


Journal

American journal of hypertension
ISSN: 1941-7225
Titre abrégé: Am J Hypertens
Pays: United States
ID NLM: 8803676

Informations de publication

Date de publication:
22 05 2021
Historique:
received: 02 08 2020
revised: 18 10 2020
accepted: 09 11 2020
pubmed: 13 11 2020
medline: 15 12 2021
entrez: 12 11 2020
Statut: ppublish

Résumé

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. 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). 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 33180898
pii: 5979473
doi: 10.1093/ajh/hpaa181
doi:

Substances chimiques

Angiogenic Proteins 0
Apolipoproteins E 0
VASH2 protein, mouse 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

467-475

Commentaires et corrections

Type : CommentIn

Informations de copyright

© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Auteurs

Nozomu Otaka (N)

Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Haruhito A Uchida (HA)

Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Michihiro Okuyama (M)

Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Saha Cardiovascular Research Center, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.

Yoshiko Hada (Y)

Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Yasuhiro Onishi (Y)

Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Yuki Kakio (Y)

Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Hidemi Takeuchi (H)

Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Ryoko Umebayashi (R)

Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Katsuyuki Tanabe (K)

Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Venkateswaran Subramanian (V)

Saha Cardiovascular Research Center, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.

Alan Daugherty (A)

Saha Cardiovascular Research Center, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.

Yasufumi Sato (Y)

Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.

Jun Wada (J)

Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

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Classifications MeSH