Angiotensin-(1-9) prevents angiotensin II-induced endothelial apoptosis through CNPY2/PERK pathway.
Apoptosis
; 28(3-4): 379-396, 2023 04.
Article
en En
| MEDLINE
| ID: mdl-36422742
ABSTRACT
Endothelial apoptosis caused by activation of renin-angiotensin system (RAS) plays a vital part in the occurrence and progress of hypertension. Angiotensin-(1-9) (Ang-(1-9)) is a peptide of the counter-regulatory non-classical RAS with anti-hypertensive effects in vascular endothelial cells (ECs). However, the mechanism of action remains unclear. Considering that the endothelial apoptosis was closely related to endoplasmic reticulum stress (ERS) and mitochondrial function. Herein, we aimed to elucidate the effects of Ang-(1-9) on endothelial apoptosis and the underlying molecular mechanism in angiotensin II (Ang II) induced hypertension. In human umbilical vascular endothelial cells (HUVECs), we observed Ang-(1-9) inhibited Ang II-induced ERS associated endothelial apoptosis. Mechanically, Ang-(1-9) inhibited endothelial apoptosis by blocking CNPY2/PERK mediated CaMKII/Drp1-dependent mitochondrial fission and eIF2α/CHOP signal. Consistent with above effects in HUVECs, in Ang II-induced hypertensive mice, we found administration of exogenous Ang-(1-9) attenuated endothelial apoptosis and arterial blood pressure, which were mediated by CNPY2/PERK signaling pathway. Our study indicated Ang-(1-9) inhibited Ang II-induced hypertension through CNPY2/PERK pathway. These findings may provide new insights for prevention and treatment of hypertension in future.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Angiotensina II
/
Hipertensión
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Apoptosis
Año:
2023
Tipo del documento:
Article
País de afiliación:
China