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

Modar Kassan, Maria Galán, Megan Partyka, Zubaida Saifudeen, Daniel Henrion, Mohamed Trebak, Khalid Matrougui

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Abstract

Cardiac damage and vascular dysfunction are major causes of morbidity and mortality in hypertension. In the present study, we explored the beneficial therapeutic effect of endoplasmic reticulum (ER) stress inhibition on cardiac damage and vascular dysfunction in hypertension. Mice were infused with angiotensin II (400 ng/kg per minute) with or without ER stress inhibitors (taurine-conjugated ursodeoxycholic acid and 4-phenylbutyric acid) for 2 weeks. Mice infused with angiotensin II displayed an increase in blood pressure, cardiac hypertrophy and fibrosis associated with enhanced collagen I content, transforming growth factor-β1 (TGF-β1) activity, and ER stress markers, which were blunted after ER stress inhibition. Hypertension induced ER stress in aorta and mesenteric resistance arteries (MRA), enhanced TGF-β1 activity in aorta but not in MRA, and reduced endothelial NO synthase phosphorylation and endothelium-dependent relaxation (EDR) in aorta and MRA. The inhibition of ER stress significantly reduced TGF-β1 activity, enhanced endothelial NO synthase phosphorylation, and improved EDR. The inhibition of TGF-β1 pathway improved EDR in aorta but not in MRA, whereas the reduction in reactive oxygen species levels ameliorated EDR in MRA only. Infusion of tunicamycin in control mice induced ER stress in aorta and MRA, and reduced EDR by a TGF-β1-dependent mechanism in aorta and reactive oxygen species-dependent mechanism in MRA. ER stress inhibition reduces cardiac damage and improves vascular function in hypertension. Therefore, ER stress could be a potential target for cardiovascular diseases.

Original languageEnglish (US)
Pages (from-to)1652-1661
Number of pages10
JournalArteriosclerosis, thrombosis, and vascular biology
Volume32
Issue number7
DOIs
StatePublished - Jul 2012

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All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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