Abstract: Objective To investigate the correlation of inducible co-stimulatory molecules (ICOS) with mesenteric vascular endothelial- mesenchymal transition (EndMT) and sclerosis in spontaneously hypertensive rats (SHR). Methods Twenty 4-week-old WKY rats and 20 SHRs of the same strain were both randomly divided into 4 groups for observation at 4, 6, 10 and 30 weeks of age. ICOS expression frequency in rat spleen CD4+ T cells was analyzed using flow cytometry, and the expressions of ICOS, VE-cad, α-SMA and Col3 mRNA in rat mesentery were detected by RT-PCR. The distributions of ICOS, IL-17A and TGF-β in rat mesentery were detected by immunohistochemistry. The levels of IL-17A and TGF-β in rat plasma were measured using ELISA. The morphological changes of rat mesenteric vessels were observed with Masson staining. Spearman or Pearson correlation analyses were used to evaluate the correlation between ICOS expression and the expressions of the markers of vascular EndMT and sclerosis. Results Compared with the control WKY rats, the SHRs began to show significantly increased systolic blood pressure and ICOS expression frequency on CD4+ T cells at 6 weeks of age (P<0.05). In the SHRs, the mRNA and protein expressions of ICOS, α-SMA, Col3, IL-17A and TGF-β in the mesentery were significantly higher than those in control group (P<0.05), while the mRNA and protein expressions of VE-cad started to reduce significantly at 10 weeks of age (P<0.05). The plasma levels of IL-17A and TGF-β were significantly increased in SHRs since 6 weeks of age (P<0.05) with progressive worsening of mesenteric vascular sclerosis (P<0.05). ICOS mRNA and protein expression levels in the mesenteric tissues of SHRs began to show positive correlations with α- SMA and Col3 expression levels and the severity of vascular sclerosis at 6 weeks of age (P<0.05) and a negative correlation with VE-cad expression level at 10 weeks (P<0.05). Conclusion ICOS play an important pathogenic role in EndMT and sclerosis of mesenteric vessels in essential hypertension by mediating related immune responses.

Key words: inducible co-stimulatory molecules; hypertension; endothelial-mesenchymal transition; vascular sclerosis