{"title":"Inflammation in cardiovascular-kidney-metabolic syndrome: key roles and underlying mechanisms-a comprehensive review.","authors":"Zhen Xu, Shuo Yang, Yuan Tan, Qian Zhang, He Wang, Jingjin Tao, Qi Liu, Qingchen Wang, Weimin Feng, Zhongxin Li, Chong Wang, Liyan Cui","doi":"10.1007/s11010-025-05379-9","DOIUrl":null,"url":null,"abstract":"<p><p>Cardiovascular-Kidney-Metabolic (CKM) syndrome, a newly defined systemic disorder, is characterized by the pathological interplay among diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD). Recent studies have identified chronic inflammation not only as a central mediator in the pathological progression of CKM syndrome but also as a pivotal molecular hub that drives coordinated damage across multiple organ systems. Mechanistic investigations have revealed that aberrant activation of signaling pathways such as NF-κB, Wnt, PI3K-AKT, JAK-STAT, and PPAR constitutes a complex inflammatory regulatory network. Notably, these pathways facilitate inter-organ inflammatory crosstalk, establishing positive feedback loops among the heart, kidneys, and metabolic tissues. This, in turn, amplifies pathological processes such as oxidative stress, endothelial dysfunction, and fibrosis in a cascading manner.This review systematically delineates the multidimensional pathophysiological mechanisms of CKM syndrome, with particular emphasis on the inter-organ inflammatory regulation mediated by key signaling pathways. Furthermore, we explore the translational potential of therapeutic strategies targeting inflammatory cytokines (e.g., IL-1β, IL-6, and TNF-α) based on the latest clinical evidence, aiming to provide a theoretical framework and novel perspectives for disrupting the vicious cycle of CKM syndrome.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Biochemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s11010-025-05379-9","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Cardiovascular-Kidney-Metabolic (CKM) syndrome, a newly defined systemic disorder, is characterized by the pathological interplay among diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD). Recent studies have identified chronic inflammation not only as a central mediator in the pathological progression of CKM syndrome but also as a pivotal molecular hub that drives coordinated damage across multiple organ systems. Mechanistic investigations have revealed that aberrant activation of signaling pathways such as NF-κB, Wnt, PI3K-AKT, JAK-STAT, and PPAR constitutes a complex inflammatory regulatory network. Notably, these pathways facilitate inter-organ inflammatory crosstalk, establishing positive feedback loops among the heart, kidneys, and metabolic tissues. This, in turn, amplifies pathological processes such as oxidative stress, endothelial dysfunction, and fibrosis in a cascading manner.This review systematically delineates the multidimensional pathophysiological mechanisms of CKM syndrome, with particular emphasis on the inter-organ inflammatory regulation mediated by key signaling pathways. Furthermore, we explore the translational potential of therapeutic strategies targeting inflammatory cytokines (e.g., IL-1β, IL-6, and TNF-α) based on the latest clinical evidence, aiming to provide a theoretical framework and novel perspectives for disrupting the vicious cycle of CKM syndrome.
期刊介绍:
Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell.
In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.