Differential expression of sphingosine-1-phosphate receptors in abdominal aortic aneurysms

Inflammation plays a key role in the pathophysiology of abdominal aortic aneurysms (AAAs). Newly discovered Sphingosine-1-Phosphate Receptors (S1P receptors) are critical in modulating inflammatory response via prostaglandin production. The aim of the current study was to investigate the expression of different S1P receptors in AAAs and compared with normal aortas at the protein level.

Aortic specimens were harvested during aortic reconstructive surgery for the AAA group or during organ transplant for the control group. The protein expression of S1P1, 2 and 3 in AAAs and normal aortas was assessed by Western blotting and immunohistochemical analysis.

There were 40 AAAs and 20 control aortas collected for the receptor analysis. For Western blot analysis, S1P1 expression was not detected in either group; S1P2 protein was constitutively detected in both types of aortas but its expression level was significantly decreased by 73% (P < 0.05) in AAAs compared with the control group. In contrast, strong S1P3 expression was detected in AAAs aortas but not in normal aortas. Immumohistochemical staining showed similar results, except a weak S1P3 signal was detectable in normal aortas.

Western blot and staining results consistently showed the down-regulation of the S1P2 protein with simultaneous up-regulation of the S1P3 protein in AAAs. Since those newly discovered receptors play an important role in the inflammatory cascade, the modulating of S1P signaling, particularly via S1P2 and S1P3, could represent novel therapeutic targets in future AAA treatments.