Soluble gp130– a serum marker for vascular remodelling?

Introduction: An increased pressure load can elicit remodeling of the cardiovascular system. Experimental data has implicated gp130, a subunit of the receptor for IL-6-related cytokines, in the regulation of proliferation and apoptosis of cardiomyocytes and vascular smooth muscle cells (VSMC). We investigated whether gp130 is involved also in humans in the vascular adaptation to elevated blood pressure.

Methods: Three populations were included in this study. A group of 48 patients with acute stroke, a group of 48 elderly control patients, and a third group of 200 healthy blood donors with an age of 18 to 66 years.

The serum concentrations of sgp130 were measured using a commercially available ELISA-Kit (Quantikine). Ultrasonographic measurement of the intima-media thickness (IMT) of the common carotid artery was performed in stroke patients and elderly controls. Blood pressure was measured on admission or before blood donation.

Immunohistochemistry was done on the aorta of male Wistar Kyoto rats and Spontaneously Hypertensive Rats (SHR).

Human vascular smooth muscle cells (VSMC) were cultured in SmGM-2 (Cambrex), supplements were added to the medium. The cells were stimulated with 1µmol/L angiotensin II Σ or 1µmol/L endothelin I (human, Sigma) and mRNA was extracted. Unstimulated sister cultures were used as controls. RNA from cultured cells was extracted with peqGOLD RNAPure^TM and real time PCR was performed.

Results: Sgp130 serum concentration correlated with blood pressure in all three study groups and with the intima-media thickness of the common carotid artery in stroke patients (sgp130-SABP stroke patients: r=0,35, p=0,015; sgp130-MABP stroke patients: r=0,38, p=0,007, in young controls: r=0,15, p=0,03; sgp130-DABP stroke patients: r=0,3, p=0,036, elderly controls: r=0,33, p=0,038, young controls r=0,14, p=0,048). Sgp130-IMT in stroke patients: r=0,47, p=0,001.

The immunohistochemistry showed the marked staining of gp130 in the aorta of SHR.

Angiotensin II stimulated gp130 mRNA accumulation (p<0.05 compared to unstimulated control).

Conclusions: The hypothesis that elevated sgp130 derives from the vascular system was supported by an enhanced expression of gp130 in the aortic wall of spontaneously hypertensive rats. Furthermore, treatment of human VSMC with angiotensin II stimulated gp130 expression. In summary, our data suggest that sgp130 serum concentrations reflect vascular remodeling in response to pressure load.