Melatonin attenuates angiotensin II-induced abdominal aortic aneurysm through the down-regulation of matrix metalloproteinases

被引：24

作者：

Kong, Jing ^{[1
,2
]}

Zhang, Ya ^{[1
,2
]}

Liu, Shanshan ^{[1
,2
]}

Li, Hongxuan ^{[1
,2
]}

Liu, Shangming ^{[3
]}

Wang, Jingjing ^{[4
]}

Qin, Xiaoteng ^{[1
,2
]}

Jiang, Xiuxin ^{[5
]}

Yang, Jianmin ^{[1
,2
]}

Zhang, Cheng ^{[1
,2
]}

Zhang, Wencheng ^{[1
,2
]}

机构：

[1] Shandong Univ, Qilu Hosp, Chinese Minist Educ, Key Lab Cardiovasc Remodeling & Funct Res, Jinan, Shandong, Peoples R China

[2] Shandong Univ, Qilu Hosp, Chinese Minist Hlth, State & Shandong Prov Joint Key Lab Translat Card, Jinan, Shandong, Peoples R China

[3] Shandong Univ, Sch Med, Dept Histol & Embryol, Key Lab,Minist Educ Expt Teratol, Jinan, Peoples R China

[4] Shandong Univ, Sch Med, Inst Pathol & Pathophysiol, Jinan, Peoples R China

[5] Shandong Univ, Qilu Hosp, Virtual Lab, Dept Gen Surg, Jinan, Peoples R China

来源：

ONCOTARGET | 2017年 / 8卷 / 09期

基金：

中国国家自然科学基金;

关键词：

abdominal aortic aneurysm; melatonin; HuR; MMP2; MMP9; Pathology Section; BINDING PROTEIN HUR; OXIDATIVE STRESS; BLOOD-PRESSURE; INHIBITION; PROTECTION; SECRETION;

D O I：

10.18632/oncotarget.15093

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Abdominal aortic aneurysm (AAA) affects more than 5% of the population in developed countries and the pharmacotherapies for AAA are limited. Here, we explored whether melatonin regulates the development of AAA. In smooth muscle cells, melatonin treatment decreases angiotensin II-induced matrix metalloproteinase 2 (MMP2) and MMP9 expression. Human antigen R (HuR) could bind with the adenylateuridylate-rich elements of MMP2 and MMP9 mRNAs 3' untranslated region, resulting in the increased stability of MMP2 and MMP9 mRNAs. HuR is required for angiotensin II-induced MMP2 and MMP9 expression. Moreover, melatonin suppresses angiotensin II-induced HuR expression through inhibiting NF-kappa B signaling, leading to decreased MMP2 and MMP9 levels. Finally, melatonin attenuates the development of AAA in ApoE(-/-) mice infused with angiotensin II in vivo. These data support a role of HuR in the development of AAA and possible therapeutic roles for melatonin and/or HuR inhibition in AAA.

引用

页码：14283 / 14293

页数：11

共 31 条

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