Gallo Giovanna, Rubattu Speranza
Department of Clinical and Molecular Medicine, Sapienza University of Rome, Via di Grottarossa 1035-1039, 00189 Rome, Italy.
Cardiology Unit, Sant'Andrea University Hospital, Via di Grottarossa 1035-1039, 00189 Rome, Italy.
Int J Mol Sci. 2025 Jun 11;26(12):5610. doi: 10.3390/ijms26125610.
Cardiac hypertrophy represents a central manifestation of hypertension-mediated organ damage (HMOD), which consists of structural and functional changes as a response to sustained pressure overload. Oxidative stress and inflammation play central roles in the development of cardiac hypertrophy, contributing to myocardial remodeling in association with mechanical stress and neurohormonal activation. The imbalance between the production of reactive oxygen species and antioxidant defense mechanisms is associated with the activation of signaling pathways and the expression of genes involved in the development and progression of cardiac fibrosis and hypertrophy. Oxidative stress is also related to mitochondrial dysfunction, redox-sensitive transcription factors, post-translational modifications, and epigenetic modulation. Novel therapeutic strategies can target these molecular pathways, reducing the impact of hypertension on HMOD. Type-2 sodium glucose transporter inhibitors were shown to restore mitochondrial bioenergetics, reducing oxidative stress, and suppressing inflammation. Also, glucagon-like peptide-1 receptor agonists reduce ROS generation and stabilize mitochondrial structure and function. In addition, vericiguat, which represents an approach targeted to restore nitric oxide-soluble guanylate cyclase signaling, might represent a valuable therapeutic approach, working to prevent and slow the progression of cardiac hypertrophy before the development of heart failure. In this review we will describe the pathophysiological mechanisms associated with cardiac hypertrophy and discuss the recent innovative therapeutic strategies with potential implications for prevention and management.
心脏肥大是高血压介导的器官损伤（HMOD）的核心表现，HMOD包括作为对持续压力过载的反应而发生的结构和功能变化。氧化应激和炎症在心脏肥大的发展中起核心作用，与机械应力和神经激素激活相关，促进心肌重塑。活性氧生成与抗氧化防御机制之间的失衡与信号通路的激活以及参与心脏纤维化和肥大发展及进展的基因表达有关。氧化应激还与线粒体功能障碍、氧化还原敏感转录因子、翻译后修饰和表观遗传调控有关。新的治疗策略可以针对这些分子途径，减少高血压对HMOD的影响。2型钠葡萄糖转运体抑制剂已被证明可恢复线粒体生物能量学，减少氧化应激，并抑制炎症。此外，胰高血糖素样肽-1受体激动剂可减少活性氧生成并稳定线粒体结构和功能。此外，维立西呱代表了一种旨在恢复一氧化氮-可溶性鸟苷酸环化酶信号传导的方法，可能是一种有价值的治疗方法，致力于在心力衰竭发生之前预防和减缓心脏肥大的进展。在本综述中，我们将描述与心脏肥大相关的病理生理机制，并讨论近期具有预防和管理潜在意义的创新治疗策略。
