Impact of insulin like growth factor-1 in development of coronary artery ectasia
Coronary artery ectasia (CAE) is characterized by inappropriate dilatation of the coronary vasculature. The mechanisms of CAE are not well known. Insulin-like growth factor-1 (IGF-1) may make endothelial cells and smooth muscle cells more sensitive to the effects of growth hormone. In the present study, we hypothesized that IGF-1 may have an impact on the formation of ectasia and aneurysm in arterial system, and aimed to investigate the associations between the presence of CAE and serum IGF-1 levels in patients undergoing coronary angiography. The study included 2.980 subjects undergoing elective diagnostic coronary angiography. We selected 40 patients diagnosed with CAE as CAE group and 44 subjects with absolutely normal coronary arteries were assigned as normal control group. IGF-1 levels were measured in both groups of patients. Groups were similar in terms of age, sex and coronary artery disease risk factors. The serum IGF-1 levels were significantly higher in CAE patients with 109.64±54.64 ng/mL than in controls with 84.76±34.01 ng/mL (p=0.016). HDL levels were lower in ectasia group with 41.5±10.7 mg/dL than controls with 47.7±10.4 mg/dL (p=0.018). By means of logistic regression analysis, high IGF-1 and low HDL levels were found to be independent risk factors for the presence of CAE (p<0.02, p<0.016, respectively). The study revealed that there was a positive correlation between serum IGF-1 levels and presence of CAE, and high IGF-1 levels and low HDL levels were independent risk factors for the presence of CAE. Future studies are needed to confirm these results.
Manginas A, Cokkinos DV. Coronary artery ectasias: imaging, functionalassessment and clinical implications. Eur Heart J 2006; 27:1026-31.
Swaye PS, Fisher LD, Litwin P, Vignola PA, Judkins MP, Kemp HG, et al. Aneurysmal coronary artery disease. Circulation 1983; 67:134-138.
Markis JE, Joffe CD, Cohn PF, Feen DJ, Herman MV, Gorlin R. Clinical signiﬁcance of coronary arterial ectasia. Am J Cardiol 1976;37:217-222.
Krüger D, Stierle U, Herrmann G, Simon R, Sheikhzadeh, A. Exercise-induced myocardial ischaemia in isolated coronary artery ectasias and aneurysms ("dilated coronaropathy"). J Am Coll Cardiol 1999;34:1461-1470.
Hartnell GG, Parnell BM, Pridie RB. Coronary artery ectasia. Its prevalence and clinical significance in 4993 patients. Br Heart J 1985; 54:392-395.
Yetkin E, Waltenberger J. Novel insights into an old controversy: is coronary artery ectasia a variant of coronary atherosclerosis? Clin Res Cardiol 2007;96:331-9.
Satran A, Bart BA, Henry CR, Murad MB, Talukdar S, Satran D, et al. Increased prevalence of coronary artery aneurysms among cocaine users. Circulation 2005;111:2424-9.
Antoniadis AP, Chatzizisis YS, Giannoglou GD. Pathogenetic mechanisms of coronary ectasia. Int J Cardiol 2008; 130:335-343.
Boles U, Rakhit R, Shiu MF, Patel K, Henein M. Coronary artery ectasia as a culprit for acute myocardial infarction: review of pathophysiology and management. Anadolu Kardiyol Derg. 2013;13:695-701.
Brunetti ND, Salvemini G, Cuculo A, Ruggiero A, De Gennaro L, Gaglione A, et al. Coronary artery ectasia is related to coronary slow flow and inflammatory activation. Atherosclerosis 2014; 233:636-640.
Turhan H, Erbay AR, Yasar AS,Aksoy Y, Bicer A, Yetkin G, et al. Plasma soluble adhesion molecules; intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin levels in patients with isolated coronary artery ectasia. Coron Artery Dis 2005; 16:45-50.
Sukhanov S, Higashi Y, Shai SY, Vaughn C, Mohler J, Li Y, et al. IGF-1reduces inflammatory responses, suppresses oxidative stress, anddecreases atherosclerosis progression in ApoE-deficient mice. ArteriosclerThromb Vasc Biol 2007; 27:2684-2690.
Higashi Y, Sukhanov S, Anwar A, Shai SY, Delafontaine P. Aging,atherosclerosis, and IGF-1. J Gerontol A Biol Sci Med Sci 2012; 67: 626-639.
Burchardt P, Gozdzicka-Jozefiak A, Zurawski J, Nowak W, Durzynska J, Link R, et al. Are Elevated Levels of IGF-1 Caused by Coronary Arteriesoclerosis?: Molecular and Clinical Analysis. Protein J 2010; 29:538-544.
Andreassen M, Raymond I, Kistorp C, Hildebrandt P, Faber J, Kristensen LO. IGF1 as predictor of all cause mortality and cardiovas¬cular disease in an elderly population. Eur J Endocrinol 2009;160:25-31.
Schuler-Luttmann S, Monnig G, Enbergs A, Schulte H, Breithardt G, Assmann G, et al. Insulin-like growth factor-binding protein-3 is associated with the presence and extent of coronary arteriosclerosis. Arterioscler Thromb Vasc Biol 2000;20:E10–E15.
Vaessen N, Heutink P, Janssen JA,Witteman JC, Testers L, Hofman A, et al. A polymorphism in the gene for IGF-1; functional properties and risk for type 2 diabetes and myocardial infarction. Diabetes 2001; 50:637-42.
Moschos SJ, Mantzoros CS. The role of IGF system in cancer: from basic to clinical studies and clinical applications. Oncology 2002; 63:317-32.
Rajpathak SN, Gunter MJ, Wylie-Rosett J, Ho GY, Kaplan RC, Muzumdar R, et al. The role of insulin-like growth factor-I and its binding proteins in glucose homeostasis and type 2 diabetes. Diabetes Metab Res Rev 2009; 25:3-12.
Krebs A, Wallaschofski H, Spilcke-Liss E, Kohlmann T, Brabant G, Völzke H, et al. Five commercially available insulin-like growth factor I (IGF-I) assays in comparison to the former Nichols Advantage IGF-I in a growth hormone treated population. Clin Chem Lab Med 2008; 46:1776-83.
American Society of Echocardiography Recommendations for Use of Echocardiography in Clinical Trials. A Report from the American Society of Echocardiography's Guidelines and Standards Committee and The Task Force on Echocardiography in Clinical Trials. J Am SocEchocardiogr 2004; 17:1086-1119.
Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 1987;316: 1371-1375
Sorrell VL, Davis MJ, Bovee AA. Origins of coronary artery ectasia. Lancet 1996;347:136-137.
Lamblin N, Bauters C, Hermant X, Lablanche JM, Helbecque N, Amouyel P. Polymorphisms in the promoter regions of MMP-2, MMP-3, MMP-9 and MMP-12 genes as determinants of aneurysmal coronary artery disease. J Am Coll Cardiol 2002;40:43-48.
Adiloglu AK, Can R, Nazlı C, Ocal A, Ergene O, Tinaz G, et al. Ectasia and severe atherosclerosis: relationships with chlamydia pneumonia, helicobacter pylori, and inflammatory markers. Tex Heart Inst J 2005; 32:21-7.
Triantafyllis AS, Kalogeropoulos AS, Rigopoulos AG, Sakadakis EA, Toumpoulis IK, Tsikrikas S, et al. Coronary artery ectasia and inflammatory cytokines: link with a predominant Th-2 immune response? Cytokine 2013; 64:427-32.
Li JJ, Nie SP, Qian XW, Zeng HS, Zhang CY. Chronic inflammatory status in patients with coronary artery ectasia. Cytokine 2009; 46:61-4.
Liu SJ, Zhong Y, You XY, Liu WH, Li AQ, Liu SM. Insulin-like growth factor 1 opposes the effects of C-reactive protein on endothelial cell activation. Mol Cell Biochem. 2014; 385:199-205.
Delafontaine P, Song YH, Li Y. Expression, regulation, and function of IGF-1, IGF-1R, and IGF-1 binding proteins in blood vessels. Arterioscler Thromb Vasc Biol 2004;24:435-44.
Song H, Mowbray AL, Sykes MC, Jo H. Emerging role of IGF-1R in stretch-induced neointimal hyperplasia in venous grafts. Arterioscler Thromb Vasc Biol 2007;27:1679-1681.
Cruzado MC, Risler NR, Miatello RM, Yao G, Schiffrin EL, Touyz RM. Vascular smooth muscle cell NAD(P)H oxidase activity during the development of hypertension: Effect of angiotensin II and role of insulinlike growth factor-1 receptor transactivation. Am J Hypertens2005; 18:81-87.
Shigematsu S, Yamauchi K, Nakajima K, Iijima S, Aizawa T, Hashizume K. IGF-1 regulates migration and angiogenesis of human endothelial cells. Endocr J1999;46:S59-S62.
Che W, Lerner-Marmarosh N, Huang Q, Osawa M, Ohta S, Yoshizumi M, et al. Insulin-like growth factor-1 enhances inflammatory responses in endothelial cells: role of Gab1 and MEKK3 in TNF-a´-induced c-Jun and NF-B activation and adhesion molecule expression. Circ Res2002; 90:1222-1230.
Wickman A, Jonsdottir IH, Bergstrom G, Hedin L. GH and IGF-I regulate the expression of endothelial nitric oxide synthase (eNOS) in cardiovascular tissues of hypophysectomized female rats. Eur J Endocrinol. 2002;147:523-533.
Lindholt JS, Martin-Ventura JL, Urbonavicius S, Ramos-Mozo P, Flyvbjerg A, Egido J, et al. Insulin-like growth factor I - a novel biomarker of abdominal aortic aneurysms. Eur J VascEndovascSurg 2011; 42:560-2.
Yeap BB, Chubb SA, McCaul KA, Flicker L, Ho KK, Golledge J, et al. Associations of IGF1 and its binding proteins with abdominal aortic aneurysm and aortic diameter in older men. Eur J Endocrinol 2012; 166:191-7.
Casini AF, Neto LV, Fontes R, França RF, Xavier SS, Gadelha MR. Aortic root ectasia in patients with acromegaly: experience at a single center. Clin Endocrinol (Oxf) 2011; 75:495-500.
Oshino S, Nishino A, Suzuki T, Arita H, Tateishi A, Matsumoto K, et al. Prevalence of cerebral aneurysm in patients with acromegaly. Pituitary 2013; 16:195-201.
Ramos-Mozo P, Rodriguez C, Pastor-Vargas C, Blanco-Colio LM, Martinez-Gonzalez J, Meilhac O, et al. Plasma profiling by a protein array approach identifies IGFBP-1 as a novel biomarker of abdominal aortic aneurysm. Atherosclerosis 2012; 221:544-50.
Sudhir K, Ports TA, Amidon TM, Goldberger JJ, Bhushan V, Kane JP, et al. Increased prevalence of coronary ectasia in heterozygous familial hypercholesterolemia. Circulation. 1995; 91:1375-80.
Altıparmak IH, Kaya Z, Sezen H, Aydın MS, Demirbağ R, Aksoy N. The relation of serum paraoxonase-1 activity with isolated coronary artery ectasia: an observational study. Anadolu Kardiyol Derg. 2012; 12:307-312.
Burchardt P, Tabaczewski P, Goździcka-Józefiak A, Siminiak T, Szczepaniak A, Banaszak A, et al. Association between insulin like growth factor-1 and lipoprotein metabolism in stable angina patients on statin therapy: a pilot study. Kardiol Pol. 2012; 70:1017-22.
Friedrich N, Nauck M, Schipf S, Völzke H, Brabant G, Wallaschofski H. Cross-sectional and longitudinal associations between insulin-like growth factor I and metabolic syndrome: a general population study in German adults. Diabetes Metab Res Rev. 2013; 29:452-62.
Elbornsson M, Götherström G, Bosæus I, Bengtsson BÅ, Johannsson G, Svensson J. Fifteen years of GH replacement improves body composition and cardiovascular risk factors. Eur J Endocrinol. 2013; 168:745-53.
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