The role and therapeutic potential of the sphingosine ⁃ 1 ⁃ phosphate signaling pathway in cardiac diseases associated with microcirculatory dysfunction
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1Department of Basic Medicine,Jiangsu Medical College,Yancheng 224005 ; 2.BioBank of Jiangsu Cancer Hospital,Nanjing 210009 ,China

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R541

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    Abstract:

    The sphingosine-1-phosphate(S1P)signaling axis plays a pivotal role in maintaining vascular homeostasis,modulating inflammatory responses,and promoting cardiomyocyte survival. However,current research has largely centered on the macrovascular and global cardiac function,with limited systematic exploration of S1P’s role in the cardiac microcirculation,a key driver of myocardial ischemia,heart failure,and fibrosis. In this review,we adopt a microcirculatory perspective to delineate the differential expression patterns and functional roles of S1P receptor subtypes in microvascular endothelial cells,vascular smooth muscle cells,and immune cell populations. We further summarize the therapeutic advances and limitations of S1P modulators,including fingolimod, siponimod,and sphingosine kinase inhibitors,in models of myocardial ischemia,heart failure,diabetic cardiomyopathy,and hypertensive heart disease. Precision intervention strategies are then proposed,integrating biomarker - guided patient stratification, receptor-subtype selective modulation,targeted nanocarrier delivery,and multi-target combination therapy. Looking ahead,single-cell spatial omics to resolve dynamic S1P receptor expression,optimized carrier design,and stratified clinical trials hold promises to accelerate the translational application of S1P pathway-based therapies in microcirculation-related cardiac diseases.

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DAI Li, ZUO Xianglin, HU Jun. The role and therapeutic potential of the sphingosine ⁃ 1 ⁃ phosphate signaling pathway in cardiac diseases associated with microcirculatory dysfunction[J].,2025,45(12):1810-1822.

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  • Received:
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  • Online: December 13,2025
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