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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
Atherosclerosis, 2012-01, Vol.220 (1), p.102-109
2012

Details

Autor(en) / Beteiligte
Titel
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
Ist Teil von
  • Atherosclerosis, 2012-01, Vol.220 (1), p.102-109
Ort / Verlag
Amsterdam: Elsevier Ireland Ltd
Erscheinungsjahr
2012
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
  • 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. Methods and 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.
Sprache
Englisch
Identifikatoren
ISSN: 0021-9150, 1879-1484
eISSN: 1879-1484
DOI: 10.1016/j.atherosclerosis.2011.10.032
Titel-ID: cdi_swepub_primary_oai_prod_swepub_kib_ki_se_123799950
Format
–
Schlagworte
Adult, Aged, Aged, 80 and over, Animals, atherosclerosis, Atherosclerosis (general aspects, experimental research), binding proteins, Biological and medical sciences, Blood and lymphatic vessels, Blood vessels and receptors, Cardiology. Vascular system, Cardiovascular, Carotid Artery Diseases - genetics, Carotid Artery Diseases - metabolism, Carotid Artery Diseases - pathology, Carotid plaque, Cell Proliferation, Cells, Cultured, correlation, ERK1/2, Female, Fundamental and applied biological sciences. Psychology, gene expression, Gene Expression Profiling - methods, Humans, IGF, IGFBP-1, iliac artery, Immunohistochemistry, in vitro studies, inflammation, Insulin-Like Growth Factor Binding Protein 1 - genetics, Insulin-Like Growth Factor Binding Protein 1 - metabolism, insulin-like growth factor I, insulin-like growth factor I receptor, insulin-like growth factor II, interleukin-1beta, Interleukin-1beta - metabolism, interleukin-6, Interleukin-6 - metabolism, macrophages, Macrophages - metabolism, Male, Medical sciences, Medicin och hälsovetenskap, messenger RNA, Middle Aged, Mitogen-Activated Protein Kinase 1 - metabolism, Mitogen-Activated Protein Kinase 3 - metabolism, Muscle, Smooth, Vascular - metabolism, Muscle, Smooth, Vascular - pathology, myocytes, Myocytes, Smooth Muscle - metabolism, Myocytes, Smooth Muscle - pathology, Oligonucleotide Array Sequence Analysis, Rats, RNA, Messenger - metabolism, SMC, smooth muscle, Somatomedins - genetics, Somatomedins - metabolism, tumor necrosis factor-alpha, Tumor Necrosis Factor-alpha - metabolism, Up-Regulation, Vertebrates: cardiovascular system

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