{"title":"The Role of the Pentose Phosphate Pathway in Cardiovascular Diseases.","authors":"Zeyu Chen, Ying Zhang, Cheng Qian, Lin Xia","doi":"10.1007/s10557-025-07788-w","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cardiovascular Drugs and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10557-025-07788-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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.