Anti-remodeling therapies in pulmonary arterial hypertension.

IF 19.9 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Trends in pharmacological sciences Pub Date : 2025-07-01 Epub Date: 2025-06-19 DOI:10.1016/j.tips.2025.05.004
Olivier Boucherat, Sébastien Bonnet, Steeve Provencher, François Potus
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引用次数: 0

Abstract

Pulmonary arterial hypertension (PAH) is a progressive, life-threatening vasculopathy characterized by sustained vasoconstriction and pathological remodeling of small pulmonary arteries. While current vasodilator therapies improve symptoms and survival, they are not curative and fail to reverse vascular remodeling. Recently, a shift toward disease-modifying strategies has emerged, driven by preclinical advances now entering clinical translation. The approval of sotatercept, the first agent presumed to target vascular remodeling, and the development of seralutinib, an inhaled tyrosine kinase inhibitor (TKI), mark key milestones. In this review, we focus on anti-remodeling therapies that have progressed from preclinical models to clinical trials. These include agents targeting cell cycle regulators, kinase pathways, epigenetic modifiers, bone morphogenetic protein receptor type 2 (BMPR2) signaling, and senescence in pulmonary arterial smooth muscle cells (PASMCs), offering renewed hope for durable PAH treatment.

肺动脉高压的抗重塑治疗。
肺动脉高压(PAH)是一种进行性、危及生命的血管病变,其特征是持续的血管收缩和小肺动脉的病理性重塑。虽然目前的血管扩张剂治疗可以改善症状和生存,但它们不能治愈,也不能逆转血管重构。最近,在临床前进展进入临床转化的推动下,一种转向疾病修饰策略的趋势已经出现。sotaterept(首个被认为是针对血管重构的药物)的批准,以及seralutinib(一种吸入型酪氨酸激酶抑制剂(TKI))的开发,标志着关键的里程碑。在这篇综述中,我们重点介绍了抗重塑治疗从临床前模型到临床试验的进展。这些药物包括靶向细胞周期调节剂、激酶通路、表观遗传修饰剂、骨形态发生蛋白受体2型(BMPR2)信号传导和肺动脉平滑肌细胞(PASMCs)衰老的药物,为持久的PAH治疗提供了新的希望。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
23.90
自引率
0.70%
发文量
132
审稿时长
6-12 weeks
期刊介绍: Trends in Pharmacological Sciences (TIPS) is a monthly peer-reviewed reviews journal that focuses on a wide range of topics in pharmacology, pharmacy, pharmaceutics, and toxicology. Launched in 1979, TIPS publishes concise articles discussing the latest advancements in pharmacology and therapeutics research. The journal encourages submissions that align with its core themes while also being open to articles on the biopharma regulatory landscape, science policy and regulation, and bioethics. Each issue of TIPS provides a platform for experts to share their insights and perspectives on the most exciting developments in the field. Through rigorous peer review, the journal ensures the quality and reliability of published articles. Authors are invited to contribute articles that contribute to the understanding of pharmacology and its applications in various domains. Whether it's exploring innovative drug therapies or discussing the ethical considerations of pharmaceutical research, TIPS provides a valuable resource for researchers, practitioners, and policymakers in the pharmacological sciences.
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