title: Increment of HFABP Level in Coronary Artery In-Stent Restenosis Segments in Diabetic and Nondiabetic Minipigs: HFABP Overexpression Promotes Multiple Pathway-Related Inflammation, Growth and Migration in Human Vascular Smooth Muscle Cells.
abstract: BACKGROUND
  Our previous study suggested that heart-type fatty acid-binding protein (HFABP) levels were greatly elevated in the conditioned medium of explant culture of in-stent restenosis (ISR) tissue from diabetic minipigs compared with those of non-ISR tissue. We here verified this result in animal tissues and investigated the impact of HFABP overexpression in human aortic smooth muscle cells (hASMCs).
  
  
  RESULTS
  In Western blot and real-time RT-PCR, HFABP protein and mRNA levels were significantly higher in ISR than in non-ISR tissues from minipigs, and higher in the ISR tissue from diabetic minipigs than that from nondiabetic minipigs. The mRNA microarray and cellular effects of hASMC retroviral overexpression of HFABP and vector was analyzed. Compared with vector, HFABP transduction activates multiple signaling pathways (e.g. adipokine, TGF-β, Toll-like receptor, Wnt, Hedgehog, ErbB and Notch) and promotes inflammation, growth and migration in hASMCs whereas the knockdown of HFABP by small hairpin RNA attenuates these effects.
  
  
  CONCLUSIONS
  HFABP expression is significantly higher in ISR tissue than in non-ISR tissue from diabetic and nondiabetic minipigs. Overexpression of HFABP induces multiple pathway-related promotion of inflammation, growth and migration in vascular SMCs, suggesting a potential role in coronary artery ISR.
authors.affiliation: Institute of Cardiovascular Diseases, Medical School of Jiaotong University, Shanghai, PR China.
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.forename: Qiu Jing
authors.initials: QJ
authors.lastname: Chen
authors.forename: Ling Jie
authors.initials: LJ
authors.lastname: Wang
authors.forename: Zhu Hui
authors.initials: ZH
authors.lastname: Liu
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.forename: Hai Bo
authors.initials: HB
authors.lastname: Wang
authors.forename: Xiao Xiang
authors.initials: XX
authors.lastname: Yan
authors.forename: Zhen Bin
authors.initials: ZB
authors.lastname: Zhu
authors.forename: Run
authors.initials: R
authors.lastname: Du
authors.forename: Rui Yan
authors.initials: RY
authors.lastname: Zhang
authors.forename: Wei Feng
authors.initials: WF
authors.lastname: Shen
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D023903:Coronary Restenosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D053263:Gene Regulatory Networks; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000295:instrumentation*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015607:Stents; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D046509:Tissue Culture Techniques; D014162:Transfection; D015854:Up-Regulation
chemical_list: C493408:FABP3 protein, human; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D018836:Inflammation Mediators; D012333:RNA, Messenger