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Abstract：
Cardiovascular disease (CVD) represents the leading cause of mortality and disability all over the world. Identifying new targeted therapeutic approaches has become a priority of biomedical research to improve patient outcomes and quality of life. The RAS-RAF-MEK (mitogen-activated protein kinase kinase)-ERK (extracellular signal-regulated kinase) pathway is gaining growing interest as a potential signaling cascade implicated in the pathogenesis of CVD. This pathway is pivotal in regulating cellular processes like proliferation, growth, migration, differentiation, and survival, which are vital in maintaining cardiovascular homeostasis. In addition, ERK signaling is involved in controlling angiogenesis, vascular tone, myocardial contractility, and oxidative stress. Dysregulation of this signaling cascade has been linked to cell dysfunction and vascular and cardiac pathological remodeling, which contribute to the onset and progression of CVD. Recent and ongoing research has provided insights into potential therapeutic interventions targeting the RAS-RAF-MEK-ERK pathway to improve cardiovascular pathologies. Preclinical studies have demonstrated the efficacy of targeted therapy with MEK inhibitors (MEKI) in attenuating ERK activation and mitigating CVD progression in animal models. In this article, we first describe how ERK signaling contributes to preserving cardiovascular health. We then summarize current knowledge of the roles played by ERK in the development and progression of cardiac and vascular disorders, including atherosclerosis, myocardial infarction, cardiac hypertrophy, heart failure, and aortic aneurysm. We finally report novel therapeutic strategies for these CVDs encompassing MEKI and discuss advantages, challenges, and future developments for MEKI therapeutics.
摘要：
心血管疾病（CVD）是全世界死亡和残疾的主要原因。确定新的靶向治疗方法已成为生物医学研究的优先事项，以改善患者的预后和生活质量。RAS-RAF-MEK（丝裂原活化蛋白激酶激酶）-ERK（细胞外信号调节激酶）途径作为与CVD发病机理有关的潜在信号级联，越来越受到人们的关注。该通路在调节细胞过程如增殖中起着关键作用，增长,迁移,分化,和生存，这对维持心血管稳态至关重要。此外,ERK信号参与控制血管生成，血管张力,心肌收缩力，和氧化应激。这种信号级联的失调与细胞功能障碍和血管和心脏病理重塑有关。这有助于CVD的发生和进展。最近和正在进行的研究提供了针对RAS-RAF-MEK-ERK途径改善心血管病理的潜在治疗干预措施的见解。临床前研究表明，在动物模型中，MEK抑制剂（MEKI）的靶向治疗在减弱ERK激活和缓解CVD进展中的功效。在这篇文章中,我们首先描述ERK信号如何有助于保持心血管健康.然后，我们总结了ERK在心脏和血管疾病的发展和进展中所起的作用的最新知识。包括动脉粥样硬化,心肌梗塞,心脏肥大,心力衰竭,和主动脉瘤。我们最后报告了包括MEKI在内的这些心血管疾病的新治疗策略，并讨论了其优势，挑战,以及MEKI治疗学的未来发展。
