Grisanti Laurel A, Guo Shuchi, Tilley Douglas G
Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
J Cardiovasc Pharmacol. 2017 Jul;70(1):3-9. doi: 10.1097/FJC.0000000000000462.
G protein-coupled receptors (GPCRs) remain primary therapeutic targets for numerous cardiovascular disorders, including heart failure (HF), because of their influence on cardiac remodeling in response to elevated neurohormone signaling. GPCR blockers have proven to be beneficial in the treatment of HF by reducing chronic G protein activation and cardiac remodeling, thereby extending the lifespan of patients with HF. Unfortunately, this effect does not persist indefinitely, thus next-generation therapeutics aim to selectively block harmful GPCR-mediated pathways while simultaneously promoting beneficial signaling. Transactivation of epidermal growth factor receptor (EGFR) has been shown to be mediated by an expanding repertoire of GPCRs in the heart, and promotes cardiomyocyte survival, thus may offer a new avenue of HF therapeutics. However, GPCR-dependent EGFR transactivation has also been shown to regulate cardiac hypertrophy and fibrosis by different GPCRs and through distinct molecular mechanisms. Here, we discuss the mechanisms and impact of GPCR-mediated EGFR transactivation in the heart, focusing on angiotensin II, urotensin II, and β-adrenergic receptor systems, and highlight areas of research that will help us to determine whether this pathway can be engaged as future therapeutic strategy.
由于G蛋白偶联受体（GPCRs）对神经激素信号升高时心脏重塑的影响，它们仍然是包括心力衰竭（HF）在内的多种心血管疾病的主要治疗靶点。GPCR阻滞剂已被证明通过减少慢性G蛋白激活和心脏重塑对HF治疗有益，从而延长HF患者的寿命。不幸的是，这种效果不会无限期持续，因此下一代疗法旨在选择性阻断有害的GPCR介导的途径，同时促进有益的信号传导。表皮生长因子受体（EGFR）的转活化已被证明由心脏中越来越多的GPCR介导，并促进心肌细胞存活，因此可能提供HF治疗的新途径。然而，GPCR依赖性EGFR转活化也已被证明通过不同的GPCR和不同的分子机制调节心脏肥大和纤维化。在这里，我们讨论心脏中GPCR介导的EGFR转活化的机制和影响，重点是血管紧张素II、尾加压素II和β-肾上腺素能受体系统，并强调有助于我们确定该途径是否可作为未来治疗策略的研究领域。
