title: The expression of IGFs and IGF binding proteins in human carotid atherosclerosis, and the possible role of IGF binding protein-1 in the regulation of smooth muscle cell proliferation.
abstract: OBJECTIVE
  Proliferation of smooth muscle cells (SMCs) in the fibrous cap of atherosclerotic lesions has been proposed to be important for plaque stability. Since the insulin-like growth factor (IGF) system has been implicated to play a role in atherosclerosis and plaque stability, we investigated the expression of members of the IGF system in carotid plaques, in particular IGFBP-1 and its role in the regulation of SMC proliferation.
  
  
  RESULTS
  Gene expression profiles of the IGF system in 164 human carotid plaques obtained from our Biobank of Karolinska Endarterectomies (BiKE) were analyzed. Expression of IGFBP-1 mRNA was significantly increased in carotid plaques compared with normal iliac arteries in contrast to IGF-1, IGF-2, and IGFBP-3 to IGFBP-6. The expression of IGFBP-1 mRNA correlated positively to that of CD163, CD68, IL-1β, IL-6, TNFα, IGFBP-4 and IGFBP-5. Immunohistochemistry demonstrated co-localization of IGFBP-1 with SMCs and macrophages. In vitro studies showed that IL-1β, IL-6 and TNFα stimulated IGFBP-1 mRNA expression in SMCs. IGFBP-1 stimulated SMC proliferation through ERK1/2 activation but independently of the IGF-1 receptor. In addition, IGFBP-1 modulated the effect of IGF-1 on SMC proliferation and ERK1/2 activation.
  
  
  CONCLUSIONS
  Our results demonstrate that IGFBP-1 mRNA and protein is detected at increased levels in human carotid plaques, possibly as a consequence of plaque inflammation. IGFBP-1 affects SMC proliferation and may be involved in the regulation of plaque stability.
authors: Division of Vascular Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Sweden. jing.wang@ki.se
authors: Jing
authors: J
authors: Wang
authors: Anton
authors: A
authors: Razuvaev
authors: Lasse
authors: L
authors: Folkersen
authors: Erika
authors: E
authors: Hedin
authors: Joy
authors: J
authors: Roy
authors: Kerstin
authors: K
authors: Brismar
authors: Ulf
authors: U
authors: Hedin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002340:Carotid Artery Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013002:Somatomedins / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C032231:IGFBP1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D013002:Somatomedins; D014409:Tumor Necrosis Factor-alpha; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3