UMMS Affiliation

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

Publication 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.

Keywords

Cardiovascular diseases, Hypertension, Mechanisms of disease

DOI of Published Version

10.1038/srep38210

Source

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

Journal/Book/Conference Title

Scientific reports

Related Resources

Link to Article in PubMed

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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