Involvement of Senescence and Mitochondrial Fission in Endothelial Cell Pro-Inflammatory Phenotype Induced by Angiotensin II
Year: 2020
Type: article
Abstract: 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 β galactosidase activity. The number of β 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.
DOI: 10.3390/ijms21093112
Institutions: Kyoto University, Temple University, Barrow Neurological Institute
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,112
Awards: G1223489781, G1474258942, Mechanism of Hypertensive Vascular Remodeling and End-Organ Damage, Mitochondrial fission mediates hypertensive vascular remodeling, Mechanisms for intracranial aneurysm rupture, The role of endothelial ADAM17 in NASH and cardiovascular disease, G4532715133, Inflammatory Responses of The Visceral Adipose Tissue Microcirculation, EGF-ADAM17 axis in the pathophysiology of intracranial aneurysm, G8207068023, G836276295, Vascular signal as a therapeutic target for abdominal aortic aneurysm, The Role of Endothelial Dysfunction and Vascular Inflammation in Hypertensive Vascular Remodeling
OpenAlex ID: W3021768649