Endothelial mechanosensing: A forgotten target to treat vascular remodeling in hypertension?

IF 5.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Biochemical pharmacology Pub Date : 2022-12-01 DOI:10.1016/j.bcp.2022.115290
Margherita Tiezzi , Hanqiang Deng , Nicolas Baeyens
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引用次数: 1

Abstract

The endothelium is a mechanosensitive organ whose pleiotropic actions regulate vessel structure to adjust tissue perfusion. To do so, it possesses ion channels, receptor complexes, and signaling pathways responding to blood flow, whose activation will either maintain vascular integrity and quiescence or, on the contrary, remodel the vessel's structure in both health and disease. Recent studies have demonstrated the crucial role of endothelial inflammation, endothelial to mesenchymal transition (EndMT), and perturbed hemodynamics in the progression of pulmonary arterial hypertension and essential hypertension. These two distinct diseases share some common mechanistic cues, pointing towards new potential therapeutic approaches to treat them. In this review, we summarize these common mechanisms to map future drug development strategies targeting flow sensing mechanisms and vascular remodeling.

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内皮力学传感:高血压血管重构治疗中被遗忘的靶点?
内皮是一种机械敏感器官,具有多种调节血管结构、调节组织灌注的功能。为此,它具有离子通道、受体复合物和响应血流的信号通路,其激活要么维持血管的完整性和静止,要么相反,在健康和疾病中重塑血管的结构。最近的研究表明,内皮炎症、内皮到间质转化(EndMT)和血流动力学紊乱在肺动脉高压和原发性高血压的进展中起着至关重要的作用。这两种截然不同的疾病有一些共同的机制线索,指出了治疗它们的新的潜在治疗方法。在这篇综述中,我们总结了这些常见的机制,以绘制未来针对血流传感机制和血管重塑的药物开发策略。
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来源期刊
Biochemical pharmacology
Biochemical pharmacology 医学-药学
CiteScore
10.30
自引率
1.70%
发文量
420
审稿时长
17 days
期刊介绍: Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics. The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process. All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review. While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.
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