TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000373304
  • Gene Name:CYSLTR1
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:qPCR
  • mRNA Pathway:NA
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB00471
  • Drug Name:Montelukast
  • Drug Method:down-regulated the gene expression

Disease basic infommation

  • Disease:obstructive sleep apnea
  • Tissue:patients tissues

Other information

  • Title:Cysteinyl-leukotriene pathway as a new therapeutic target for the treatment of atherosclerosis related to obstructive sleep apnea syndrome
  • Journal:Pharmacological Research
  • Published:2018
  • PubMed ID:29920371
  • Abstract:Aims:Obstructive sleep apnea (OSA) characterized by nocturnal intermittent hypoxia (IH) is associated with atherosclerosis and cysteinyl-leukotrienes (CysLT) pathway activation. We aimed to identify the determinants of CysLT pathway activation and the role of CysLT in OSA-related atherosclerosis. Methods and results:Determinants of the urinary excretion of LTE4(U-LTE4) including history of cardiovascular events, polysomnographic and biological parameters were studied in a cohort of 170 OSA patients and 29 controls, and in a subgroup of OSA patients free of cardiovascular event (n = 136). Mechanisms linking IH, the CysLT pathway and atherogenesis were investigated in Apolipoprotein E deficient (ApoE-/-) mice exposed to 8-week IH. In the whole cohort, U-LTE4was independently influenced by age, minimal oxygen saturation, and a history of cardiovascular events, and correlated significantly with intima-media thickness. In the subgroup of OSA patients free of cardiovascular event, increased U-LTE4was increased compared to controls and independently related to hypoxia severity and traditional risk factors aggregated in the 10-year cardiovascular risk score of European Society of Cardiology. In IH mice, atherosclerosis lesion size and mRNA levels of 5-lipoxygenase, 5-lipoxygenase activating protein (FLAP) and CysLT1receptor were significantly increased. This transcriptional activation was associated with the binding of HIF-1 to the FLAP promoter and was strongly associated with atherosclerosis lesion size. CysLT1receptor antagonism (montelukast) significantly reduced atherosclerosis progression in IH mice. Conclusions:IH-related CysLT pathway activation contributes to OSA-induced atherogenesis. In the era of personalized medicine, U-LTE4may be a useful biomarker to identify OSA patients for whom CysLT1blockade could represent a new therapeutic avenue for reducing cardiovascular risk.
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