CONICET | Buscador de Institutos y Recursos Humanos

The gper is a g protein couple receptor was an orphan receptor until some investigators proposed the estrogen and the aldosterone as ligand of this receptor. Also it has been proposed that activation of gper is responsible of the no genomic effect of aldo and estrogen. The activation of gper protects the heart against injury. For example, reduced the infart size, reduce the fibrosis and fibrolast proliferation. In this study we tested the hypothesis that the activation of GPER by the specific agonist G-1, reduce the hypertrophy. We used neonatal rat cardiac myocytes cultures, and we used as a model of hypertrophy aldo. It is well known that ald through the activation of MR increase the cell size. As we can see here in figure 1, ald increase the cell size and the hypertrophy induced by aldosterone was abrogated by epl an antagonist of mr o by sirna against mr. Now, we coincubated the cells with aldos and g-1the agonist of gper. As we can g-1 reduced the hypertrophy induced by ald, as we can see in the cell size of in the bnp expression. And this reduction of the hypertrophy was by the activation of gper because as we can see here, when we used an sirna against gper and incubate with ald, the g-1 failed to reduce the hypertrophy by aldo. The activation of gper not only prevent the hypertrophy as we saw before, we can regress it when it is already established. In this experiments, first we incubated the cells with ald, we measure the size to corroborate the hypertrophy and then we start the treatment with g-1. Clearly the g-1 regress the hypertrophy when it is already established. Then we change to another model, an in vivo one. We used shr rats as a hypertrophy in vivo model. We treated this rats with g-1 for 28 days, with an osmotic mini pumps. In this figure of the cross section area or the bnp expression, we can see how the activation of gper significantly reduced the hypertrophy of the rats, without any change in blood pressure, indicating that the effect of g-1 is directly to the myocytes. We measure the expression of the gper and mr in the rats, and we cannot found any differences, also any differences were found in the collagen content. The echocardiographic studies reveal a reduction of left ventricular end diastolic and en systolic diameter and a reduction of the left ventricular mass index.Taken together, the results that I showed you today demonstrated that the activation of gper reduced the hypertrophy induced by aldosterone.