Statins as Modulators of Epithelial to Mesenchymal Transition in Cardiovascular-Kidney-Metabolic Syndrome: a...

Cardiovascular-kidney-metabolic (CKM) syndrome involves complex interactions among cardiovascular, renal, and metabolic disorders. This review provides an overview of the mechanistic aspects of the epithelial-mesenchymal transition (EMT) and analyzes the regulatory impact of various statins on EMT-associated signaling pathways.

EMT and endothelial-to-mesenchymal transition (EndoMT) are crucial in the development of cardiac fibrosis, vascular remodeling, and interstitial fibrosis. Several signaling pathways, including the TGF-β/Smad, Wnt/β-catenin, MAPK, and Notch signaling pathways, as well as oxidative stress and inflammatory mediators, regulate these processes. Statins exert significant biological effects by downregulating proinflammatory cytokines, suppressing ROS, and inhibiting EMT-related signaling pathways. Statins can also inhibit EndoMT and reduce the progression of vascular fibrosis and atherosclerosis in the context of cardiovascular diseases. Similarly, in renal disorders such as chronic kidney disease (CKD) and diabetic nephropathy, statins reduce EMT in renal tubular epithelial cells by targeting pathways such as Smad and MAPK. CKM syndrome involves complex interactions among cardiovascular, renal, and metabolic disorders. Among the factors implicated in the pathophysiology of CKM, the EMT process is recognized as a key biological process. Evidence from preclinical and clinical studies supports the emerging role of statins as promising agents in managing CKM through modulating EMT. Therefore, understanding the diverse mechanisms of statins may lead to the development of more effective therapeutic strategies against CKM's fibrotic and inflammatory complications.