Are elevated levels of IGF-1 caused by coronary arteriesoclerosis?: Molecular and clinical analysis.

The importance of insulin-like growth factor-1 (IGF-1) in coronary artery disease (CAD) due to wide range of its biological effects and its therapeutic potential, has already been described. Our aim was to evaluate possible influence of IGF-1 serum level changes on coronary atherosclerosis. In case of existence of such association our further aim was to verify and explain this phenomenon by examination of promoter P1 of IGF-1gene and receptor gene for IGF-1. The study was performed in 101 consecutive patients undergo for routine coronary angiography. Quantitative and qualitative assessment of coronary atherosclerosis was performed respectively by estimation of the number of culprit lesions in coronary arteries and by Gensini score calculation. IGF-1, IGFBP3 and plasma lipoproteins were measured in all patients. In addition, we evaluated DNA from 101 patients, isolated from blood cells, which was amplified by using PCR with sophisticated primers for P1 promoter of IGF-1 gene and IGF-1 receptor gene, then analyzed utilizing SSCP technique and automatically sequenced. We observed significant increase of serum IGF-1 levels in patients with "3 vessel disease" and with high score in Gensini scale when compared to those without any narrowing lesions in coronary arteries and 0 Gensini score (in group with 3 vessel disease 215.0 ± 71.3 versuss 176.7 ± 34.2 ng/ml p = 0.04 and with high Gensini score 231.4 ± 59.3 versus 181.0 ± 37.8 ng/ml p = 0.01).We found different genotypes for five P1 promoter polymorphisms of IGF-1 gene (RS35767, RS5742612, RS228837, RS11829693, RS17879774). There were no significant associations between the observed single nucleotide polymorphism (SNP) and coronary atherosclerosis nor with levels of circulating IGF-1. We found no structural polymorphism in receptor gene for IGF-1 nor in its extracellular domain(exon 2-4) nor in internal domain (exon 16-21). The effect of increased IGF-1 serum level in our study was probably independent from structural polymorphism in promoter P1 for IGF-1 or in receptor gene for IGF-1.

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.

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.