Background: We investigated whether serum level of C1q/TNF-related protein (CTRP) 5 is associated with in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation, and assessed the biological effects of CTRP5 in human aortic smooth muscle cells (hASMCs).
Methods and results: Serum CTRP5 levels were assayed in 306 patients with and 306 patients without angiographic ISR at approximately one year after DES-based PCI. Multivariate logistic regression analysis was performed to determine risk factors for ISR. Notably, serum CTRP5 levels were higher in ISR patients than in non-ISR counterparts (197±84ng/mL vs. 150±74ng/mL, P<0.001). Compared with the lowest tertile (<125ng/mL) of CTRP5, patients with the mid (125-200ng/mL) and the highest tertile (>200ng/mL) of CTRP5 had a more than 1.6-fold (adjusted OR=1.670-2.127, P≤0.039) and 7.4-fold (adjusted OR=7.478-11.264, all P<0.001) increased risk of ISR (all P for trend <0.001), respectively, after adjustment for potential clinical, biochemical and angiographic characteristics. To assess the biological effects of CTRP5, we stimulated hASMCs with this protein. CTRP5 concentration-dependently induced the expression of MMP-2, cyclin D1 and TNF-α in hASMCs, with activation of Notch1, TGF-β and hedgehog signaling pathways. Consistently, this protein promoted migration and proliferation of hASMCs in wound-healing, Boyden chamber and Brdu incorporation assay.
Conclusion: Increased serum CTRP5 level is associated with ISR after PCI with DES implantation. CTRP5 promotes proliferation, inflammation and migration in vascular smooth muscle cells through activation of multiple pathways.
Keywords: C1q/TNF-related protein; Drug-eluting stent; Percutaneous coronary intervention; Restenosis.
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