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

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• 作者：Ying Shen ; Chang Li ; Rui Yan Zhang ; Qi Zhang ; Wei Feng Shen ; Feng Hua Ding ; ^{ruijindfh@126.com} ; Lin Lu ; ^{rjlulin1965@163.com}
• 关键词：Percutaneous coronary intervention ; Drug-eluting stent ; Restenosis ; C1q/TNF-related protein
• 刊名：International Journal of Cardiology
• 出版年：2017
• 出版时间：1 February 2017
• 年：2017
• 卷：228
• 期：Complete
• 页码：129-136
• 全文大小：1040 K
• 卷排序：228

文摘

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 resultsSerum 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 ± 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-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.ConclusionIncreased 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.