TGF-β 作为梗塞和衰竭心脏的治疗靶点:细胞机制、挑战和机遇。

IF 4.6 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Expert Opinion on Therapeutic Targets Pub Date : 2024-01-01 Epub Date: 2024-02-19 DOI:10.1080/14728222.2024.2316735
Nikolaos G Frangogiannis
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引用次数: 0

摘要

简介心肌纤维化伴随着大多数心脏疾病,可以是修复性的,也可以是适应性不良的。转化生长因子(TGF)-β是一种强效的纤维化介质,参与损伤心脏的修复、重塑和纤维化:本综述手稿讨论了 TGF-β 在心力衰竭中的作用,重点关注细胞机制和治疗意义。TGF-β在梗塞、重塑和衰竭的心脏中被激活。除了纤维化作用外,TGF-β 还对心肌细胞、免疫细胞和血管细胞产生广泛的影响,这些影响可能具有保护性后果,也可能具有损害性后果。TGF-β 介导的对巨噬细胞的作用可促进抗炎转换,而对成纤维细胞的作用则介导修复性瘢痕的形成,对周皮细胞的作用则参与梗死新血管的成熟。另一方面,TGF-β对心肌细胞的作用会促进不良重塑,成纤维细胞中 TGF-β 信号的长期激活会刺激纤维化和心力衰竭的发展:专家观点:要为心肌病患者设计治疗策略,就必须了解 TGF-β 的细胞特异性作用。此外,要对不同类型的心力衰竭患者实施治疗干预,还需要对高心衰患者和高心衰患者进行机制驱动的分类。如果心衰患者的纤维化 TGF-β 反应持续时间过长或过度活跃,那么他们可能会从谨慎的 TGF-β 抑制中获益。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
TGF-β as a therapeutic target in the infarcted and failing heart: cellular mechanisms, challenges, and opportunities.

Introduction: Myocardial fibrosis accompanies most cardiac conditions and can be reparative or maladaptive. Transforming Growth Factor (TGF)-β is a potent fibrogenic mediator, involved in repair, remodeling, and fibrosis of the injured heart.

Areas covered: This review manuscript discusses the role of TGF-β in heart failure focusing on cellular mechanisms and therapeutic implications. TGF-β is activated in infarcted, remodeling and failing hearts. In addition to its fibrogenic actions, TGF-β has a broad range of effects on cardiomyocytes, immune, and vascular cells that may have both protective and detrimental consequences. TGF-β-mediated effects on macrophages promote anti-inflammatory transition, whereas actions on fibroblasts mediate reparative scar formation and effects on pericytes are involved in maturation of infarct neovessels. On the other hand, TGF-β actions on cardiomyocytes promote adverse remodeling, and prolonged activation of TGF-β signaling in fibroblasts stimulates progression of fibrosis and heart failure.

Expert opinion: Understanding of the cell-specific actions of TGF-β is necessary to design therapeutic strategies in patients with myocardial disease. Moreover, to implement therapeutic interventions in the heterogeneous population of heart failure patients, mechanism-driven classification of both HFrEF and HFpEF patients is needed. Heart failure patients with prolonged or overactive fibrogenic TGF-β responses may benefit from cautious TGF-β inhibition.

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来源期刊
CiteScore
8.90
自引率
1.70%
发文量
58
审稿时长
3 months
期刊介绍: The journal evaluates molecules, signalling pathways, receptors and other therapeutic targets and their potential as candidates for drug development. Articles in this journal focus on the molecular level and early preclinical studies. Articles should not include clinical information including specific drugs and clinical trials. The Editors welcome: Reviews covering novel disease targets at the molecular level and information on early preclinical studies and their implications for future drug development. Articles should not include clinical information including specific drugs and clinical trials. Original research papers reporting results of target selection and validation studies and basic mechanism of action studies for investigative and marketed drugs. The audience consists of scientists, managers and decision makers in the pharmaceutical industry, academic researchers working in the field of molecular medicine and others closely involved in R&D.
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