Endoplasmic reticulum stress is involved in cardiac damage and vascular endothelial dysfunction in hypertensive mice

Area of Science:

• Cardiovascular Research
• Molecular Medicine
• Hypertension Studies

Background:

• Hypertension significantly contributes to cardiovascular morbidity and mortality through cardiac damage and vascular dysfunction.
• Endoplasmic reticulum (ER) stress is implicated in the pathophysiology of hypertension-related cardiovascular complications.

Purpose of the Study:

• To investigate the therapeutic potential of inhibiting ER stress in mitigating cardiac damage and vascular dysfunction in a mouse model of hypertension.

Main Methods:

• Angiotensin II infusion was used to induce hypertension in mice, with or without ER stress inhibitors (taurine-conjugated ursodeoxycholic acid and 4-phenylbutyric acid).
• Cardiac hypertrophy, fibrosis, ER stress markers, blood pressure, and vascular function (endothelium-dependent relaxation, EDR) in aorta and mesenteric resistance arteries (MRA) were assessed.
• Specific pathways including transforming growth factor-β1 (TGF-β1) and reactive oxygen species (ROS) were analyzed.

Main Results:

• Angiotensin II infusion increased blood pressure, cardiac hypertrophy, fibrosis, and ER stress markers, all of which were attenuated by ER stress inhibition.
• Hypertension-induced ER stress in the aorta and MRA was associated with altered TGF-β1 activity and reduced endothelial NO synthase phosphorylation and EDR.
• ER stress inhibition improved EDR by reducing TGF-β1 activity and enhancing endothelial NO synthase phosphorylation, while ROS reduction ameliorated EDR in MRA.

Conclusions:

• Inhibition of ER stress demonstrates significant therapeutic benefits against cardiac damage and vascular dysfunction in hypertension.
• ER stress represents a viable therapeutic target for managing cardiovascular diseases associated with hypertension.