Skip to main content

Advertisement

SpringerLink
Log in

Presence of irregularity in region between −1115 and −784 nt in P1 promoter of Insulin-Like Growth Factor-1 gene may indicate beneficial effect on coronary arteries in a group of patients with stable angina: preliminary data

  • Original Article
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Abstract

Insulin-like growth factor-1 (IGF-1) plays an important role in arterial homeostasis. Its properties seem to depend on circulating IGF-1 level changes. The various IGF-1 levels are caused by varied expression of IGF-1 gene, due to the polymorphic structure of IGF-1 gene or its regulatory sequences. We examined the P1 promoter, being responsible for most IGF-1 transcripts, in patients with stable angina, to evaluate its sequence changes and to assess its influence on protein synthesis as well as on the degree of arteriosclerosis. For that purpose we evaluated the DNA isolated from blood cells. The DNA was amplified by using polymerase chain reaction (PCR), then analyzed using the SSCP (single-strand conformation polymorphism) technique. Products of every stage were verified by electrophoresis on agarose gel. In addition, every patient had coronary angiography performed and IGF-1, IGFBP3, and lipid levels measured. The SSCP in the region between −1115 and −784 nt was less commonly observed among subjects with positive MI (myocardial infarction) familial history (P = 0.0008) and with MI history (P = 0.012) than in patients without these conditions. Subjects with this irregularity tended towards higher circulating IGF-1 levels. In addition high Gensini scores — over 95th percentile, 105 points in our study — were more frequent in SSCP patients (P = 0.03). We presume that presence of SSCP in the P1 region between −1115 and −784 nt may positively affect coronary arteries by increasing circulating IGF-1 levels, but its clinical importance requires molecular verification and further studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Delafontaine P, Song Y-H, Li Y (2004) Expression, regulation, and function of IGF-1, IGF-1R, and IGF-1 binding proteins in blood vessels. Arterioscler Thromb Vasc Biol 24:435–444

    Article  CAS  PubMed  Google Scholar 

  2. Burchardt P, Gozdzicka-Jozefiak A, Siminiak T (2006) IGF-1 — a new risk factor for coronary atherosclerosis. Kardiol Pol 64:1297–1302

    PubMed  Google Scholar 

  3. Van der Wal AJ, Becker AE (1999) Atherosclerotic plaque rupture-pathologic basis of plaque stability and instability. Cardiovasc Res 41:334–344

    Article  PubMed  Google Scholar 

  4. Bolster D, Kim S, Jefferson L (2004) Regulation of protein synthesis associated with skeletal muscle hypertrophy by insulin-, amino acid- and exercise-induced signaling ball. Proc Nutr Soc 63:351–356

    Article  CAS  PubMed  Google Scholar 

  5. Bienertova-Vasku JA, Vasku OHA (2007) Are common leptin promoter polymorphisms associated with restenosis after coronary stenting? Heart Vessels 22:310–315

    Article  PubMed  Google Scholar 

  6. Mizia-Stec K, Gasior Z, Zahorska-Markiewiez B, Holecki M, Kumor P (2006) Inflammatory markers in a 2-year follow-up of coronary artery disease. Heart Vessels 21:302–308

    Article  PubMed  Google Scholar 

  7. Yazdanpanah M, Rietveld I, Janssen J, Njajou O, Hofman A, Stijnen T, Pols H, Lamberts S, Witteman J, van Duijn C (2006) An insulin-like growth factor-1 promoter polymorphism is associated with increased mortality in subjects with myocardial infarction in an elderly caucasian population. Am J Cardiol 97:1274–1276

    Article  CAS  PubMed  Google Scholar 

  8. Vaessen N, Heutink P, Janssen JA, Witteman J, Testers L, Hofman A, Lamberts S, Oostra B, Pols H, Duijn C (2001) A polymorphism in the gene for IGF-1 functional properties and risk for type 2 diabetes and myocardial infarction. Diabetes 50:697–704

    Article  Google Scholar 

  9. Withers DJ, Burks DJ, Towery HH, Altamuro SL, Flint CL, White MF (1999) IRS-2 coordinates IGF-1 receptor-mediated-cell development and peripheral insulin signaling. Nat Genet 23:32–40

    CAS  PubMed  Google Scholar 

  10. Tsuruzoe K, Emkey R, Kriauciunas KM, Ueki K, Kahn C (2001) Insulin receptor substrate 3 (IRS-3) and IRS-4 impair IRS-1- and IRS-2-mediated signaling. Mol Cell Biol 21:26–38

    Article  CAS  PubMed  Google Scholar 

  11. Isenovic ER, Meng Y, Divald A, Milivojevic N, Sowers JR (2002) Role of phosphatidylinositol 3-kinase/Akt pathway in angiotensin and insulin-like growth factor-1 modulation of nitric oxide synthesis in vascular smooth muscle cells. Endocrine 19:287–292

    Article  CAS  PubMed  Google Scholar 

  12. Castrillo A, Bodelon OG, Bosca L (2000) Inhibitory effect of IGF-1 on type 2 nitric oxide synthase expression in Ins-1 cells and protection against activation dependent apoptosis: involvement of phosphatidylinositol 3-kinase. Diabetes 49:209–217

    Article  CAS  PubMed  Google Scholar 

  13. LeRoith D, Werner H, Beitner-Johnson, Roberts CT Jr (1995) Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev 16:143–163

    CAS  PubMed  Google Scholar 

  14. Saltiel AR, Kahn CR (2001) Insulin signaling and the regulation of glucose and lipid metabolism. Nature 414:799–806

    Article  CAS  PubMed  Google Scholar 

  15. Schini-Kerth VB (1999) Dual effects of insulin-like growth factor-1 on the constitutive and inducible nitric oxide (NO) synthase-dependent formation of NO in vascular cells. J Endocrinol Invest 22:82–88

    CAS  PubMed  Google Scholar 

  16. Michell BJ, Griffiths JE, Mitchelhill KI, Rodriguez-Crespo I, Tiganis T, Bozinovski S, de Montellano PR, Kemp BE, Pearson RB (1999) The Akt kinase signals directly to endothelial nitric oxide synthase. Curr Biol 9:845–848

    Article  CAS  PubMed  Google Scholar 

  17. Renier G, Clement I, Desfaits AC, Lambert A (1996) Direct stimulatory effect of insulin-like growth factor I on monocyte and macrophage tumor necrosis-a production. Endocrinology 137: 4611–4618

    Article  CAS  PubMed  Google Scholar 

  18. Hochberg Z, Hertz P, Maor G, Oiknine J, Aviram M (1992) Growth hormone and insulin-like growth factor I increase macrophage uptake and degradation of low-density lipoprotein. Endocrinology 131:430–435

    Article  CAS  PubMed  Google Scholar 

  19. Juul A, Scheike T, Davidsen M, Gyllenborg J, Jørgensen T (2002) Low serum insulin-like growth factor I is associated with increased risk of ischemic heart disease: a population-based case-control study. Circulation 106:939–944

    Article  CAS  PubMed  Google Scholar 

  20. Janssen JA, Stolk RP, Pols HA, Grobbee DE, Lamberts SW (1998) Serum total IGF-I, free IGF-I, and IGFB-1 levels in an elderly population: relation to cardiovascular risk factors and disease. Arterioscler Thromb Vasc Biol 18:277–282

    CAS  PubMed  Google Scholar 

  21. Grant MB, Wargovich TJ, Ellis EA, Caballero S, Mansour M, Pepine CJ (1996) Expression of IGF-I, IGF-I receptor and IGF binding proteins-1, -2, -3, -4 and -5 in human atherectomy specimens. Regul Pept 67:137–144

    Article  CAS  PubMed  Google Scholar 

  22. Okura Y, Brink M, Zhadi AA, Anwar A, Delafontaine P (2001) Decreased expression of insulin-like growth factor-1 and apoptosis of vascular smooth muscle cells in human atherosclerotic plaque. J Mol Cell Cardiol 33:1777–1789

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biology and Environmental Sciences, Division of Cardiology — Intensive Therapy Department of Internal Medicine, University School of Medicine, Poznan, Poland

    Pawel Burchardt

  2. Department of Biology, University of Adam Mickiewicz, Poznan, Poland

    Witold Nowak & Anna Gozdzicka-Jozefiak

  3. Kowanowko Cardiac and Rehabilitation Hospital, Kowanowko, Poland

    Rafal Link & Tomasz Grotowski

  4. Department of Communication Sciences, University of Connecticut, Storrs, CT, USA

    Anna Wisniecka

  5. Kowanowko Cardiac and Rehabilitation Hospital, University of Medical Sciences, Kowanowko, Poland

    Tomasz Siminiak

  6. ul. Szczesna 4c, 60-587, Poznan, Poland

    Pawel Burchardt

Authors
  1. Pawel Burchardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Witold Nowak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anna Gozdzicka-Jozefiak
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tomasz Grotowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anna Wisniecka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tomasz Siminiak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pawel Burchardt.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Burchardt, P., Nowak, W., Gozdzicka-Jozefiak, A. et al. Presence of irregularity in region between −1115 and −784 nt in P1 promoter of Insulin-Like Growth Factor-1 gene may indicate beneficial effect on coronary arteries in a group of patients with stable angina: preliminary data. Heart Vessels 24, 254–259 (2009). https://doi.org/10.1007/s00380-008-1116-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00380-008-1116-z

Key words

Search

Navigation