title: 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.
abstract: 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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Institute of Cardiovascular Diseases, Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Institute of Cardiovascular Diseases, Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Chang
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Institute of Cardiovascular Diseases, Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Rui Yan
authors.initials: RY
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Institute of Cardiovascular Diseases, Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Institute of Cardiovascular Diseases, Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Wei Feng
authors.initials: WF
authors.lastname: Shen
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Institute of Cardiovascular Diseases, Jiaotong University School of Medicine, Shanghai, People's Republic of China. Electronic address: ruijindfh@126.com.
authors.forename: Feng Hua
authors.initials: FH
authors.lastname: Ding
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Institute of Cardiovascular Diseases, Jiaotong University School of Medicine, Shanghai, People's Republic of China. Electronic address: rjlulin1965@163.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
mesh_terms: D003094:Collagen / Q000097:blood*; D017023:Coronary Angiography / Q000706:statistics & numerical data; D023903:Coronary Restenosis / Q000097:blood / Q000175:diagnosis / Q000209:etiology; D054855:Drug-Eluting Stents / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000503:physiopathology; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects* / Q000295:instrumentation / Q000379:methods; D012307:Risk Factors; D015398:Signal Transduction; D013223:Statistics as Topic
chemical_list: C487851:C1QTNF5 protein, human; D003094:Collagen
keywords: C1q/TNF-related protein; Drug-eluting stent; Percutaneous coronary intervention; Restenosis