戊糖磷酸途径在心血管疾病中的作用。

IF 3.1 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Zeyu Chen, Ying Zhang, Cheng Qian, Lin Xia
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引用次数: 0

摘要

心血管疾病(cvd)是全球死亡的主要原因,其特点是多因素病因涉及多种细胞类型,如心肌细胞和免疫细胞。心肌细胞和免疫细胞的代谢重编程参与了心血管疾病的病理生理,其中戊糖磷酸途径(PPP)起着关键作用。PPP主要产生烟酰胺腺嘌呤二核苷酸磷酸(NADPH)和5-磷酸核糖(R5P)。NADPH不仅通过再生还原型谷胱甘肽(GSH)和硫氧还蛋白(Trx)来维持细胞的抗氧化能力,而且在特定条件下通过NADPH氧化酶(NOX)参与活性氧(ROS)的产生,从而发挥心脏保护和氧化损伤的双重作用。同时,R5P参与核苷酸生物合成,支持细胞周期进程和免疫细胞扩增。因此,PPP是细胞增殖和功能所必需的。在心肌细胞中,PPP增强可减少氧化应激,促进心肌修复。PPP调节免疫细胞的表型和功能,并参与炎症反应和组织修复。针对PPP关键酶的治疗干预,如葡萄糖-6-磷酸脱氢酶(G6PDH),可以减轻cvd的氧化损伤,减少病理性纤维化,并调节免疫细胞活性。一些G6PDH抑制剂,如脱氢表雄酮和6-氨基烟酰胺(6-AN),处于临床前阶段。这篇综述强调PPP在心血管疾病中的重要性,提倡有针对性的代谢治疗,以提高心血管疾病的治疗效果和患者预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Role of the Pentose Phosphate Pathway in Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are the leading contributors to global mortality, characterized by multifactorial etiology involving diverse cell types such as cardiomyocytes and immune cells. Metabolic reprogramming in cardiomyocytes and immune cells is involved in the pathophysiology of CVDs, and the pentose phosphate pathway (PPP) plays a critical role. The PPP mainly generates nicotinamide adenine dinucleotide phosphate (NADPH) and ribose-5-phosphate (R5P). NADPH not only maintains cellular antioxidant capacity by regenerating reduced glutathione (GSH) and thioredoxin (Trx) but also participates in reactive oxygen species (ROS) production through NADPH oxidases (NOX) under specific conditions, thus exerting dual roles in cardioprotection and oxidative damage. Meanwhile, R5P contributes to nucleotide biosynthesis, supporting cell cycle progression and immune cell expansion. Therefore, PPP is necessary for cellular proliferation and function. In cardiomyocytes, enhanced PPP reduces oxidative stress and facilitates myocardial repair. The PPP modulates phenotypes and functions in immune cells and is involved in inflammatory responses and tissue repair. Therapeutic interventions targeting key enzymes of the PPP, like glucose-6-phosphate dehydrogenase (G6PDH), can alleviate oxidative damage, reduce pathological fibrosis, and modulate immune cell activity in CVDs. Some inhibitors of G6PDH, such as dehydroepiandrosterone and 6-amino-nicotinamide (6-AN), are in the preclinical stage. This review emphasizes the importance of the PPP in CVDs, advocating for targeted metabolic therapies to enhance treatment efficacy and patient outcomes in CVDs.

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来源期刊
Cardiovascular Drugs and Therapy
Cardiovascular Drugs and Therapy 医学-心血管系统
CiteScore
8.30
自引率
0.00%
发文量
110
审稿时长
4.5 months
期刊介绍: Designed to objectively cover the process of bench to bedside development of cardiovascular drug, device and cell therapy, and to bring you the information you need most in a timely and useful format, Cardiovascular Drugs and Therapy takes a fresh and energetic look at advances in this dynamic field. Homing in on the most exciting work being done on new therapeutic agents, Cardiovascular Drugs and Therapy focusses on developments in atherosclerosis, hyperlipidemia, diabetes, ischemic syndromes and arrhythmias. The Journal is an authoritative source of current and relevant information that is indispensable for basic and clinical investigators aiming for novel, breakthrough research as well as for cardiologists seeking to best serve their patients. Providing you with a single, concise reference tool acknowledged to be among the finest in the world, Cardiovascular Drugs and Therapy is listed in Web of Science and PubMed/Medline among other abstracting and indexing services. The regular articles and frequent special topical issues equip you with an up-to-date source defined by the need for accurate information on an ever-evolving field. Cardiovascular Drugs and Therapy is a careful and accurate guide through the maze of new products and therapies which furnishes you with the details on cardiovascular pharmacology that you will refer to time and time again.
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