Association of increased serum CTRP5 levels with in-stent restenosis after coronary drug-eluting stent implantation: CTRP5 promoting inflammation, migration and proliferation in vascular smooth muscle cells

作者：Shen, Ying; Li, Chang; Zhang, Rui Yan; Zhang, Qi; Shen, Wei Feng; Ding, Feng Hua^*; Lu, Lin^*

来源：International Journal of Cardiology, 2017, 228: 129-136.

DOI：10.1016/j.ijcard.2016.11.034

• Percutaneous coronary intervention
• Drug-eluting stent
• Restenosis
• C1q/TNF-related protein

Background: We investigated whether serum level of C1q/TNF-related protein (CTRP) 5 is associated with instent 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: SerumCTRP5 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 +/- 84 ng/mL vs. 150 +/- 74 ng/mL, P < 0.001). Compared with the lowest tertile (<125 ng/mL) of CTRP5, patients with the mid (125-200 ng/mL) and the highest tertile (>200 ng/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-alpha in hASMCs, with activation of Notch1, TGF-beta 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.

• 出版日期2017-2-1
• 单位上海市闵行区中心医院