Interleukin33 deficiency exacerbated Angiotensin II-induced Abdominal Aortic Aneurysms but had no effect on Thoracic Aortic Aneurysms nor Angiotensin II-induced atherosclerosis in male Apolipoprotein E-deficient mice.
Abstract Body: Objective: Chronic infusion of angiotensin II (AngII) promotes development of abdominal aortic aneurysms (AAAs) as well as atherosclerosis in Apolipoprotein E-deficient mice (SKO mice). Interleukin 33 (IL-33), known as one of IL-1 family, is rapidly released from damaged endothelial and epithelial cells. The purpose of this study was to evaluate the effect of IL-33 deficiency on development of AAAs and atherosclerosis. Methods and Results: IL-33 deficient (IL-33-/-) and ApoE deficient (ApoE-/-) mice were bred to generate IL-33-/-xApoE-/- mice (DKO mice). Male SKO and DKO were assigned to saline infused group (SKO n=5, DKO n=7) and AngII infused group (SKO n=19, DKO n=19). Eight- to twelve-week-old mice were infused subcutaneously with either saline or AngII (1,000 ng/kg/min) by osmotic minipumps for 4 weeks. During 4-week AngII infusion, three mice died by AAA rupture in each AngII-infused group. No significant difference was observed in ex vivo abdominal aortic width nor body weight between saline infused groups. AngII equally elevated systolic BP (SKO 151±15 mmHg, DKO 155±17 mmHg, n.s.). AngII significantly increased ex vivo maximum abdominal aortic width in SKO mice. This effect was further exacerbated in DKO mice (SKO 1.31±0.09 mm, DKO 1.76±0.09 mm, p=0.001). Moreover, the severity of AAAs was significantly worse in DKO than in SKO (p=0.037). AngII increased en face atherosclerosis in AngII-infused groups, but no significant difference was found in the atherosclerosis between AngII-infused groups (SKO 4.4±1.0 %, DKO 4.7±0.8 %, n.s.). Similarly, AngII also increased Thoracic Aortic Aneurysms (TAAs) in AngII-infused groups, but no significant difference was found in TAAs between AngII-infused groups (SKO 1.58±0.13 mm, DKO 1.62±0.12 mm, n.s.). Interestingly, as we conducted further research on Tregs, we found that the number of FoxP3+/CD4+ cells in aortas was significantly reduced in DKO mice (SKO: 6.4±1.9/1×105 μm2, DKO: 1.5±0.4/1×105 μm2, p<0.001). Conclusion: The impact of IL-33 deficiency in the development of Ang II-induced vascular pathologies differs among AAAs, TAAs and atherosclerosis.
Asakawa, Tomohiko
(
Okayama University Faculty of Medine, Dentistry, and Pharmaceutical Science, Okayama
, Okayama , Okayama , Japan )
Umebayashi, Ryoko
(
Okayama University Faculty of Medine, Dentistry, and Pharmaceutical Science, Okayama
, Okayama , Okayama , Japan )
Sakurabu, Yoshimasa
(
Okayama University Faculty of Medine, Dentistry, and Pharmaceutical Science, Okayama
, Okayama , Okayama , Japan )
Katayama, Katsuyoshi
(
Okayama University Faculty of Medine, Dentistry, and Pharmaceutical Science, Okayama
, Okayama , Okayama , Japan )
Okamoto, Shugo
(
Okayama University Faculty of Medine, Dentistry, and Pharmaceutical Science, Okayama
, Okayama , Okayama , Japan )
Onishi, Yasuhiro
(
Okayama University Faculty of Medine, Dentistry, and Pharmaceutical Science, Okayama
, Okayama , Okayama , Japan )
Matsuoka-uchiyama, Natsumi
(
Okayama University Faculty of Medine, Dentistry, and Pharmaceutical Science, Okayama
, Okayama , Okayama , Japan )
Takeuchi, Hidemi
(
Okayama University Faculty of Medine, Dentistry, and Pharmaceutical Science, Okayama
, Okayama , Okayama , Japan )
Uchida, Haruhito
(
Okayama University Faculty of Medine, Dentistry, and Pharmaceutical Science, Okayama
, Okayama , Okayama , Japan )
Author Disclosures:
Tomohiko Asakawa:DO NOT have relevant financial relationships
| Ryoko Umebayashi:No Answer
| Yoshimasa Sakurabu:DO NOT have relevant financial relationships
| Katsuyoshi Katayama:No Answer
| Shugo Okamoto:No Answer
| Yasuhiro Onishi:No Answer
| Natsumi matsuoka-uchiyama:No Answer
| Hidemi Takeuchi:DO NOT have relevant financial relationships
| Haruhito Uchida:No Answer
