Chronic infusion of ELABELA alleviates vascular remodeling in spontaneously hypertensive rats via anti-inflammatory, anti-oxidative and anti-proliferative effects.
Acta Pharmacol Sin
; 43(10): 2573-2584, 2022 Oct.
Article
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| MEDLINE
| ID: mdl-35260820
Inflammatory activation and oxidative stress promote the proliferation of vascular smooth muscle cells (VSMCs), which accounts for pathological vascular remodeling in hypertension. ELABELA (ELA) is the second endogenous ligand for angiotensin receptor-like 1 (APJ) receptor that has been discovered thus far. In this study, we investigated whether ELA regulated VSMC proliferation and vascular remodeling in spontaneously hypertensive rats (SHRs). We showed that compared to that in Wistar-Kyoto rats (WKYs), ELA expression was markedly decreased in the VSMCs of SHRs. Exogenous ELA-21 significantly inhibited inflammatory cytokines and NADPH oxidase 1 expression, reactive oxygen species production and VSMC proliferation and increased the nuclear translocation of nuclear factor erythroid 2-related factor (Nrf2) in VSMCs. Osmotic minipump infusion of exogenous ELA-21 in SHRs for 4 weeks significantly decreased diastolic blood pressure, alleviated vascular remodeling and ameliorated vascular inflammation and oxidative stress in SHRs. In VSMCs of WKY, angiotensin II (Ang II)-induced inflammatory activation, oxidative stress and VSMC proliferation were attenuated by pretreatment with exogenous ELA-21 but were exacerbated by ELA knockdown. Moreover, ELA-21 inhibited the expression of matrix metalloproteinase 2 and 9 in both SHR-VSMCs and Ang II-treated WKY-VSMCs. We further revealed that exogenous ELA-21-induced inhibition of proliferation and PI3K/Akt signaling were amplified by the PI3K/Akt inhibitor LY294002, while the APJ receptor antagonist F13A abolished ELA-21-induced PI3K/Akt inhibition and Nrf2 activation in VSMCs. In conclusion, we demonstrate that ELA-21 alleviates vascular remodeling through anti-inflammatory, anti-oxidative and anti-proliferative effects in SHRs, indicating that ELA-21 may be a therapeutic agent for treating hypertension.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Hormonas Peptídicas
/
Remodelación Vascular
/
Hipertensión
Límite:
Animals
Idioma:
En
Revista:
Acta Pharmacol Sin
Asunto de la revista:
FARMACOLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos