RRML - Function of the S1P pathway in hypoxia-induced cardiovascular failure

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Nr. 32(1)/2024 DOI:10.2478/rrlm-2023-0006

Research article

Function of the S1P pathway in hypoxia-induced cardiovascular failure

Fangping Zhou, Weihong Tang

Correspondence should be addressed to: Weihong Tang

Abstract:

Background: Vascular failure (VF) and heart failure (HF) are extremely harmful and are the primary causes of hypoxia. Our previous results have shown that the sphingosine-1-phosphate (S1P) pathway was involved in regulating intermittent hypoxia–induced vascular defection, but the clinical role and molecular mechanism of the S1P pathway remain unclear. Methods: Normalized relative expression values and differentially expressed genes were downloaded in GSE145221 from the Gene Expression Omnibus dataset. WGCNA was used to construct a gene co-expression network. The Spearman correlation matrix was used to identify the top 500 highly correlated genes with the S1P pathway genes. R package clusterProfiler was used to perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses on the WGCNA modules. Homer software was utilized to identify regulatory motifs in the promoter and gene body regions of S1P pathway genes. An intermittent hypoxic injury cell model was induced by chronic intermittent hypoxia (CIH). ROS and TUNEL staining and Western blot were used to detect cell apoptosis and reactive oxygen species. Results: The transcriptional regulatory regions of S1P pathway genes were enriched with hypoxia-inducible factor 1-alpha, which indicated the close connection between the S1P pathway and the CIH process. In vitro, we confirmed that the endothelial cell apoptosis induced by CIH could be reversed by exogenous addition of S1P. Conclusions: This study elucidated the mechanism of the S1P pathway in regulating cardiovascular injury caused by CIH and provided a new strategy for early intervention in people with cardiovascular dysfunction induced by hypoxia.

Keywords: sphingosine-1-phosphate, hypoxia, vascular failure, heart failure; atherosclerosis, sleep-disordered breathing

Received: 12.12.2023
Accepted: 9.1.2024
Published: 16.1.2024

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Zhou F, Tang W. Function of the S1P pathway in hypoxia-induced cardiovascular failure. Rev Romana Med Lab. 2024;32(1):69-80. DOI:10.2478/rrlm-2023-0006