UMMS Affiliation

Division of Cardiovascular Medicine, Department of Medicine; UMass Metabolic Network

Date

12-2-2016

Document Type

Article

Disciplines

Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology

Abstract

Endothelial dysfunction is a characteristic of many vascular related diseases such as hypertension. Peroxisome proliferator activated receptor gamma, coactivator 1alpha (PGC-1alpha) is a unique stress sensor that largely acts to promote adaptive responses. Therefore, we sought to define the role of endothelial PGC-1alpha in vascular function using mice with endothelial specific loss of function (PGC-1alpha EC KO) and endothelial specific gain of function (PGC-1alpha EC TG). Here we report that endothelial PGC-1alpha is suppressed in angiotensin-II (ATII)-induced hypertension. Deletion of endothelial PGC-1alpha sensitized mice to endothelial dysfunction and hypertension in response to ATII, whereas PGC-1alpha EC TG mice were protected. Mechanistically, PGC-1alpha promotes eNOS expression and activity, which is necessary for protection from ATII-induced dysfunction as mice either treated with an eNOS inhibitor (LNAME) or lacking eNOS were no longer responsive to transgenic endothelial PGC-1alpha expression. Finally, we determined that the orphan nuclear receptor, estrogen related receptor alpha (ERRalpha) is required to coordinate the PGC-1alpha -induced eNOS expression. In conclusion, endothelial PGC-1alpha expression protects from vascular dysfunction by promoting NO* bioactivity through ERRalpha induced expression of eNOS.

Rights and Permissions

Citation: Sci Rep. 2016 Dec 2;6:38210. doi: 10.1038/srep38210. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Keywords

Cardiovascular diseases, Hypertension, Mechanisms of disease

PubMed ID

27910955

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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