Figure 2.
GPER in the functional circle of diastology of the female heart. Diastolic function is an appropriate barometer of overall heart health as it reflects cellular and subcellular events responsible for maintaining myocardial relaxation, cardiomyocyte calcium homeostasis, mitochondrial bioenergetics, antioxidant defense, left ventricular (LV) and myocyte structure, and proximal aortic distensibility. Loss of ovarian estrogens due to aging/menopause or surgery lead to impairments in myocardial/cardiomyocyte relaxation, increased mitochondrial reactive oxygen species and impaired oxidant defenses and bioenergetics, hypertrophic and/or interstitial remodeling, and aortic stiffening. Preclinical studies show that activation of the non-canonical estrogen receptor, GPER, by its agonist G1 or estradiol (E2) favorably regulates and likely integrates components of relaxation, mitochondrial function, LV structure, LV ejection, and aortic compliance, to preserve diastolic function in the female heart.