Research ArticleCardiovascular Biology

Obligatory role for GPER in cardiovascular aging and disease

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Science Signaling  01 Nov 2016:
Vol. 9, Issue 452, pp. ra105
DOI: 10.1126/scisignal.aag0240

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Preventing the ravages of ROS

Ligand-dependent activation of the G protein–coupled estrogen receptor (GPER) has been reported to confer cardiovascular benefits. However, Meyer et al. found that genetic absence of Gper conferred protection from cardiovascular pathologies associated with aging and hypertension. GPER activity was required to increase the abundance of the enzyme Nox1 in vascular smooth muscle cells, blood vessels, and myocardium, and was associated with enhanced production of tissue-damaging superoxide. Aged mice that were deficient in Gper developed much less cardiac fibrosis and hypertrophy and also retained greater cardiovascular function. In addition, a pharmacological inhibitor of GPER reduced blood pressure, superoxide production, and Nox1 abundance in hypertensive mice. Thus, inhibitors of GPER are potential therapies for cardiovascular diseases and conditions characterized by excessive superoxide generation.