Centro de Investigaciones Cardiovasculares "Dr. Horacio Cingolani", Facultad de Ciencias Médicas, Universidad Nacional de La Plata-CONICET, La Plata, Argentina.
Servicio de Cardiología, Facultad de Veterinaria, Universidad Nacional de La Plata, La Plata, Argentina.
Life Sci. 2020 Feb 1;242:117211. doi: 10.1016/j.lfs.2019.117211. Epub 2019 Dec 28.
Ventricular hypertrophy is a risk factors for arrhythmias, ischemia and sudden death. It involves cellular modifications leading to a pathological remodeling and is associated with heart failure. The activation of the G protein-coupled estrogen receptor (GPER) mediates beneficial actions in the cardiovascular system. Our goal was to prevent and regress the hypertrophy by the activation of GPER in neonatal cardiac myocytes (NRCM) and SHR male rats. Aldosterone increased the neonatal cardiomyocytes cell surface area after 48 h of incubation. The aldo-induced hypertrophy was blocked by the mineralocorticoid receptor (MR) inhibitor Eplererone or the reduction of MR expression by siRNA. The activation of GPER by the agonist G-1 totally prevented the increase surface area by Ald. The transfection of neonatal rat cardiac myocytes with a siRNA against GPER or the incubation with GPER blockers G-15 and G-36 inhibited the protection of G-1. The significant increase of cell surface area after 48 h of incubation with Ald was totally regressed in 24 h by the presence of G-1, indicating that the activation of GPER not only prevent the hypertrophy but also regress the hypertrophy when it is already established. In the in vivo model, G-1 or Vehicle was constantly infused via the minipump to SHR. The reduction of the hypertrophy by G-1 was evident by the cross-sectional area, BNP and ANP markers and by echocardiography. In this studied we demonstrated that the activation of GPER prevented and regressed the hypertrophy induced by Ald in NRCM and regressed hypertrophy in SHR rats.
心室肥厚是心律失常、缺血和猝死的危险因素。它涉及导致病理性重塑的细胞改变，并与心力衰竭有关。G 蛋白偶联雌激素受体 (GPER) 的激活介导了心血管系统的有益作用。我们的目标是通过激活新生大鼠心肌细胞 (NRCM) 和自发性高血压大鼠 (SHR) 中的 GPER 来预防和逆转肥厚。醛固酮在孵育 48 小时后增加了新生心肌细胞的细胞表面积。醛固酮诱导的肥大被盐皮质激素受体 (MR) 抑制剂 Eplererone 或 siRNA 降低 MR 表达所阻断。激动剂 G-1 激活 GPER 可完全阻止 Ald 引起的表面积增加。用针对 GPER 的 siRNA 转染新生大鼠心肌细胞或用 GPER 阻滞剂 G-15 和 G-36 孵育可抑制 G-1 的保护作用。Ald 孵育 48 小时后细胞表面积的显著增加在 24 小时内被 G-1 完全消退，表明 GPER 的激活不仅可以预防肥厚，而且当肥厚已经形成时也可以逆转肥厚。在体内模型中，G-1 或载体通过微量泵持续输注到 SHR。G-1 减少了心肌肥厚的横截面积、BNP 和 ANP 标志物和超声心动图。在本研究中，我们证明了 GPER 的激活可预防和逆转 NRCM 中 Ald 诱导的肥厚，并可逆转 SHR 大鼠的肥厚。
