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Angiotensin-II activates vascular inflammasome and induces vascular damage.

Authors :
Cau SB
Bruder-Nascimento A
Silva MB
Ramalho FNZ
Mestriner F
Alves-Lopes R
Ferreira N
Tostes RC
Bruder-Nascimento T
Source :
Vascular pharmacology [Vascul Pharmacol] 2021 Aug; Vol. 139, pp. 106881. Date of Electronic Publication: 2021 Jun 09.
Publication Year :
2021

Abstract

Angiotensin-II (Ang-II), a major target for treatment of cardiovascular disease, promotes cardiovascular dysfunction by directly modulating structure and function of vascular cells. Inflammasome components are expressed in the vasculature and are activated by specific stimuli. However, whether Ang-II activates the inflammasome in vascular cells or inflammasome activation contributes to Ang-II-induced vascular damage is still not fully elucidated. We tested the hypothesis that Ang-II induces endothelial dysfunction, vascular remodeling, and high blood pressure via inflammasome activation. C57BL6/J wild type (WT) and Caspase-1 knockout (Casp1-/-) mice were infused with vehicle or Ang-II for two weeks (490 ng/Kg/day) to determine whether the inflammasome contributes to vascular damage induced by Ang-II. Rat Aortic Vascular Smooth Muscle cells (RASMC) were used to determine if the interaction between Ang-II and inflammasomes causes migration and proliferation of vascular smooth muscle cells. Ex vivo studies revealed that Ang-II infusion induced vascular oxidative stress, endothelial dysfunction and vascular remodeling in WT mice. Casp1-/- mice were protected against Ang-II-induced vascular injury. In vitro experiments, Ang-II activated the NLRP3 inflammasome in RASMC, i.e. Ang-II increased Caspase-1 (Casp1) activity and cleavage of pro-interleukin (IL)-1β. MCC950 (NLRP3 receptor antagonist) prevented Ang-II-induced vascular migration and proliferation, but failed to reduce reactive oxygen species production. In conclusion, Ang-II leads to inflammasome activation in the vasculature contributing to endothelial dysfunction and vascular remodeling. Taken together, we place inflammasomes as a possible therapeutic target in conditions associated with increased Ang-II levels.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1879-3649
Volume :
139
Database :
MEDLINE
Journal :
Vascular pharmacology
Publication Type :
Academic Journal
Accession number :
34098096
Full Text :
https://doi.org/10.1016/j.vph.2021.106881