Involvement of Senescence and Mitochondrial Fission in Endothelial Cell Pro-Inflammatory Phenotype Induced by Angiotensin II

被引：33

作者：

Miyao, Masashi ^{[1
,2
]}

Cicalese, Stephanie ^{[1
]}

Kawai, Tatsuo ^{[1
]}

Cooper, Hannah A. ^{[1
]}

Boyer, Michael J. ^{[1
]}

Elliott, Katherine J. ^{[1
]}

Forrester, Steven J. ^{[1
]}

Kuroda, Ryohei ^{[1
]}

Rizzo, Victor ^{[1
]}

Hashimoto, Tomoki ^{[3
]}

Scalia, Rosario ^{[1
]}

Eguchi, Satoru ^{[1
]}

机构：

[1] Temple Univ, Lewis Katz Sch Med, Cardiovasc Res Ctr, 3500 N Broad St, Philadelphia, PA 19140 USA

[2] Kyoto Univ, Grad Sch Med, Dept Forens Med, Sakyo Ku, Yoshida Konoe Cho, Kyoto 6068501, Japan

[3] Barrow Neurol Inst, Dept Neurosurg & Neurobiol, Barrow Aneurysm & AVM Res Ctr, Phoenix, AZ 85013 USA

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2020年 / 21卷 / 09期

基金：

日本学术振兴会;

关键词：

endothelial cells; angiotensin II; senolytic; ER stress; inflammation; ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; SIGNAL-TRANSDUCTION; MECHANISMS; RECEPTOR; DRP1; CONTRIBUTES; DYSFUNCTION; APOPTOSIS; MDIVI-1;

D O I：

10.3390/ijms21093112

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Angiotensin II (AngII) has a crucial role in cardiovascular pathologies, including endothelial inflammation and premature vascular aging. However, the precise molecular mechanism underlying aging-related endothelial inflammation induced by AngII remains elusive. Here, we have tested a hypothesis in cultured rat aortic endothelial cells (ECs) that the removal of AngII-induced senescent cells, preservation of proteostasis, or inhibition of mitochondrial fission attenuates the pro-inflammatory EC phenotype. AngII stimulation in ECs resulted in cellular senescence assessed by senescence-associated beta galactosidase activity. The number of beta galactosidase-positive ECs induced by AngII was attenuated by treatment with a senolytic drug ABT737 or the chemical chaperone 4-phenylbutyrate. Monocyte adhesion assay revealed that the pro-inflammatory phenotype in ECs induced by AngII was alleviated by these treatments. AngII stimulation also increased mitochondrial fission in ECs, which was mitigated by mitochondrial division inhibitor-1. Pretreatment with mitochondrial division inhibitor-1 attenuated AngII-induced senescence and monocyte adhesion in ECs. These findings suggest that mitochondrial fission and endoplasmic reticulum stress have causative roles in endothelial senescence-associated inflammatory phenotype induced by AngII exposure, thus providing potential therapeutic targets in age-related cardiovascular diseases.

引用

页数：13

共 45 条

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