Endoplasmic Reticulum Chemical Chaperone 3-Hydroxy-2-Naphthoic Acid Reduces Angiotensin II-Induced Vascular...

Area of Science:

• Cardiovascular Research
• Molecular Biology
• Pharmacology

Background:

• Current hypertension treatments inadequately reduce cardiovascular disease risk.
• Chronic endoplasmic reticulum stress and unfolded protein response (UPR) are implicated in hypertension and vascular remodeling.
• Targeting UPR offers a potential therapeutic strategy for hypertension.

Purpose of the Study:

• To investigate the efficacy of 3-hydroxy-2-naphthoic acid (3HNA), a novel chemical chaperone, in attenuating angiotensin II (AngII)-induced hypertension and vascular remodeling.
• To determine if 3HNA can mitigate the cellular consequences of AngII stimulation.

Main Methods:

• Angiotensin II (AngII) infusion in mice to induce hypertension and vascular remodeling over two weeks.
• Administration of 3HNA with or without AngII infusion.
• Histological assessment of vascular structure and fibrosis.
• In vitro studies on cultured vascular smooth muscle cells and adventitial fibroblasts.

Main Results:

• 3HNA treatment prevented the development of hypertension and cardiac hypertrophy in AngII-infused mice.
• Histological analysis showed 3HNA inhibited vascular medial thickening and perivascular fibrosis.
• In vitro, 3HNA reduced AngII-induced protein synthesis in vascular smooth muscle cells and UPR markers in fibroblasts.

Conclusions:

• 3HNA effectively prevents AngII-induced hypertension and vascular remodeling in mice.
• 3HNA mitigates key cellular responses, including protein synthesis and UPR activation, under cardiovascular stress.
• 3HNA shows promise as a novel therapeutic agent for hypertension, potentially by preserving protein homeostasis.