Whole blood levels of S1PR4 mRNA associated with cerebral vasospasm after aneurysmal subarachnoid hemorrhage

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  • 1 Sorbonne Université, UPMC, INSERM UMR_S 1166, F-75013, Paris;
  • 2 ICAN Institute for Cardiometabolism and Nutrition, Paris;
  • 3 Department of Anesthesia and Intensive Care, Pitié-Salpetrière Hospital, Assistance, Publique-Hopitaux de Paris, Paris;
  • 4 Université Paris 7, INSERM UMR 1141, Paris;
  • 5 INSERM UMR_S 1219, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux;
  • 6 Sorbonne Université, UPMC, Groupe de Recherche Clinique Biosfast, Paris; and;
  • 7 Department of Neuroradiology, Pitié-Salpêtrière Hospital, Paris, France
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OBJECTIVE

The authors sought to identify mRNA biomarkers of cerebral vasospasm in whole blood of patients suffering from aneurysmal subarachnoid hemorrhage (aSAH).

METHODS

A prospective transcriptomic study for vasospasm was conducted in whole blood samples of 44 aSAH patients who developed (VSP+ group, n = 22) or did not develop (VSP group, n = 22) vasospasm. Samples from all patients were profiled for 21,460 mRNA probes using the Illumina Human HT12v4.0 array. Differential statistical analysis was performed using a linear mixed model.

RESULTS

Levels of sphingosine-1-phosphate receptor 4 (S1PR4) mRNA were significantly higher (p = 8.03 × 10−6) at presentation in patients who developed vasospasm after aSAH than in patients who did not.

CONCLUSIONS

The results, which are consistent with findings of previous experimental investigations conducted in animal models, support the role of S1PR4 and its ligand, sphingosine-1-phosphate (S1P), in arterial-associated vasoconstriction, which suggests that S1PR4 could be used as a biomarker for cerebral vasospasm in aSAH patients.

ABBREVIATIONS aSAH = aneurysmal subarachnoid hemorrhage; D0 = day of admission; Dv3 = 3 days before the day VSP+ patients experienced vasospasm (or the corresponding day for the matched VSP− patients); miRNA = microRNA; S1P = sphingosine-1-phosphate; S1PR4 = sphingosine-1-phosphate receptor 4; TCD = transcranial Doppler; VSP = vasospasm patient group.

Supplementary Materials

    • Supplementary Tables 1–5 (ZIP 2.52 MB)

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Contributor Notes

Correspondence David-Alexandre Trégouët: INSERM UMR_S 1219, Bordeaux Population Health Research Center, Bordeaux, France. david-alexandre.tregouet@inserm.fr.

INCLUDE WHEN CITING Published online November 29, 2019; DOI: 10.3171/2019.9.JNS191305.

V.D. and D.A.T. contributed equally to this work.

Disclosures Dr. Clarençon reports personal and consultant or advisory relationships, including paid lectures, with Balt, Medtronic, and Penumbra.

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