肺动脉高压的信号通路和靶向治疗

IF 40.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Joseph Adu-Amankwaah, Yue Shi, Hequn Song, Yixuan Ma, Jia Liu, Hao Wang, Jinxiang Yuan, Kun Sun, Qinghua Hu, Rubin Tan
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引用次数: 0

摘要

肺动脉高压(PH)是一个以高死亡率为特征的全球性健康问题。目前治疗PH的主要靶点集中在前列环素、一氧化氮和内皮素途径。虽然针对这些途径的方法构成了标准PH治疗的基础,但挑战仍然是开发更有效的治疗策略。PH病理特征的证据表明,其他细胞信号通路也参与增殖、凋亡、细胞外基质重塑、线粒体功能障碍、炎症、内皮向间质转化、铁下垂、焦下垂以及内皮细胞、平滑肌细胞、成纤维细胞和巨噬细胞之间复杂的细胞相互作用网络。在这篇综述中,我们探讨了20个关键信号通路在PH发病机制中的作用。此外,一些通路之间的串扰提供了对PH复杂机制的更详细理解。考虑到信号通路在PH进展中的关键作用,靶向这些异常信号通路或其中心分子为减轻PH病理提供了巨大的潜力。这篇综述深入探讨了针对关键信号通路和网络相互作用的PH的各种治疗方法,包括基因治疗、细胞治疗和药物干预。在动物研究和临床试验证据的支持下,这些策略旨在逆转肺血管的病理改变并恢复其正常功能,解决与PH相关的重大健康挑战。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Signaling pathways and targeted therapy for pulmonary hypertension

Signaling pathways and targeted therapy for pulmonary hypertension

Pulmonary hypertension (PH) is a global health issue characterized by high mortality. The main targets for current therapies in PH focus on the prostacyclin, nitric oxide, and endothelin pathways. While the approaches targeting these pathways form the foundation of standard PH treatment, the challenge remains to develop more effective therapeutic strategies. Evidence of pathological characteristics in PH illustrates other cell signaling pathways that also participate in the proliferation, apoptosis, extracellular matrix remodeling, mitochondrial dysfunction, inflammation, endothelial-to-mesenchymal transition, ferroptosis, pyroptosis, and the intricate network of cell-cell interactions of endothelial cells, smooth muscle cells, fibroblasts, and macrophages. In this review, we explore the roles of twenty key signaling pathways in PH pathogenesis. Furthermore, the crosstalks among some pathways offer a more detailed understanding of the complex mechanisms of PH. Considering the crucial role of signaling pathways in PH progression, targeting these aberrant signaling or their hub molecules offers great potential for mitigating PH pathology. This review delves into a variety of therapeutic approaches for PH that target critical signaling pathways and network interactions, including gene therapy, cell therapy, and pharmacological interventions. Supported by evidence from both animal studies and clinical trials, these strategies aim to reverse pathological alterations in pulmonary vessels and restore their normal function, addressing the significant health challenges associated with PH.

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来源期刊
Signal Transduction and Targeted Therapy
Signal Transduction and Targeted Therapy Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
44.50
自引率
1.50%
发文量
384
审稿时长
5 weeks
期刊介绍: Signal Transduction and Targeted Therapy is an open access journal that focuses on timely publication of cutting-edge discoveries and advancements in basic science and clinical research related to signal transduction and targeted therapy. Scope: The journal covers research on major human diseases, including, but not limited to: Cancer,Cardiovascular diseases,Autoimmune diseases,Nervous system diseases.
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