Atherosklerose: Verlust des Sphingosin-1-phosphat-Rezeptors 3 im Menschen

Greulich, S.; Winter, C.; Odinga, M.; Ring, S.; Geissen, M.; Wipper, S.; Keil, W.; Debus, E. S.; Daum, G. und Larena-Avellaneda, A. (2021): Atherosklerose: Verlust des Sphingosin-1-phosphat-Rezeptors 3 im Menschen. In: Gefasschirurgie, Bd. 26, Nr. 4: S. 281-289

Abstract

Background and aim Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates important functions in the vasculature including vascular permeability and vascular tone. The overall objective of this study was to investigate whether the expression of the S1P receptor 3 (S1PR3) is associated with atherosclerosis in humans. Methods Tissue samples from 6 arteries (coronary artery, carotid artery, the ascending aorta, the descending aorta, the abdominal aorta and iliac artery) were collected from 163 randomly chosen subjects during autopsies. Based on autopsy protocols, the plaque burden was scored for each artery (0 = none, 1 = soft plaque, 2 = hard plaque). For each subject a cumulative plaque score (CPS) was calculated by the addition of all individual scores. The expression of S1PR3 was measured by qPCR. Spearman correlation coefficients were calculated to detect potential correlations between clinical and epidemiological parameters with S1PR3 expression. Results The expression of S1PR3 differed between the various arteries, generally declined with age, most profoundly in coronary arteries (r = -0.225, p < 0.01) and was independent of gender. The highest S1PR3 expression levels were found in the coronary artery and the lowest in the descending aorta. With increasing atherosclerotic burden S1PR3 expression in all arteries responded similarly: it first remained almost unchanged (CPS 0-4) before it decreased between CPS 4-6 by about 50% (-0.8 log2%). A further increase of CPS no longer affected S1PR3 expression. The sharp decrease of S1PR3 expression was statistically independent of age. Conclusion Increasing CPS is accompanied by a systemic decrease of S1PR3 expression. This observation opens up the possibility that vascular S1PR3 expression may be used as a marker for atherosclerosis progression. Moreover, an S1PR3 agonist could represent a novel pharmacological approach to slow atherosclerosis progression;however, further studies are necessary before this approach can be implemented.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0948-7034
• Sprache: Deutsch