S1PR1 knockdown protects endothelial cells from oxidized low-density lipoprotein-induced injury via reducing interleukin-1β and tumor necrosis factor-α expression

Abstract

BACKGROUND

Coronary atherosclerotic heart disease (CAHD) is a prevalent cardiovascular condition. Recent research has uncovered the significant role of sphingosine-1-phosphate receptor 1 (S1PR1) in cardiovascular disorders, including atherosclerosis, acute myocardial infarction, myocardial ischemia, and reperfusion.

AIM

To explore the clinical relevance, diagnostic utility, and molecular mechanisms of S1PR1 in CAHD.

METHODS

The expression of S1PR1 was examined by quantitative real-time polymerase chain reaction. Cytokines in serum were detected by flow cytometry using a twelve-cytokine detection kit. Receiver operating characteristic curves were employed to assess the diagnostic value of S1PR1, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α in CAHD. The cell counting kit-8 assay was utilized to determine cell viability, and flow cytometry was used to detect cell apoptosis. Western blot analysis was conducted to detect the protein levels of S1PR1.

RESULTS

S1PR1 was highly expressed in CAHD, with significantly higher levels observed in the high Gensini score group (≥ 40) compared to the low score group (< 40). Compared with the healthy control group, the CAHD group exhibited significantly increased levels of IL-1β and TNF-α, no significant difference in IL-2 and IL-6 levels, and a significant decrease in the levels of other cytokines. Furthermore, a correlation was observed between S1PR1 and both IL-1β and TNF-α in CAHD. The receiver operating characteristic curve analysis demonstrated that the combined detection of S1PR1, IL-1β, and TNF-α exhibited superior diagnostic value for CAHD compared to individual tests. Additionally, in oxidized low-density lipoprotein-treated human umbilical vein endothelial cells, the expressions of S1PR1, IL-1β, and TNF-α were increased. However, knockdown of S1PR1 resulted in decreased expression of IL-1β and TNF-α, accompanied by enhanced cell viability and attenuated apoptosis.

CONCLUSION

S1PR1 could act as a new diagnostic and monitoring biomarker for CAHD. Knockdown of S1PR1 protected human umbilical vein endothelial cells from oxidized low-density lipoprotein-induced injury, which is mediated through regulation of IL-1β and TNF-α expression.

Keywords: Sphingosine-1-phosphate receptor 1; Coronary atherosclerotic heart disease; Oxidized low-density lipoprotein; Interleukin-1β; Tumor necrosis factor-α

Core Tip: In this study, sphingosine-1-phosphate receptor 1 (S1PR1) is upregulated in coronary atherosclerotic heart disease and positively correlates with interleukin-1β and tumor necrosis factor-α. It serves as a promising diagnostic biomarker, and combined detection with inflammatory cytokines enhances diagnostic performance. S1PR1 knockdown alleviates oxidized low-density lipoprotein-induced endothelial cell injury via modulating inflammatory responses, highlighting S1PR1 as a potential target for coronary atherosclerotic heart disease diagnosis and intervention.