bFGF and TGFbeta1 growth factors, inflammatory markers (IL-6, TNF-alpha, CRP) and advanced glycation end-products (AGE, RAGE) in patients with ischemic heart disease and type 2 diabetes mellitus

Aims.
To evaluate plasma levels of transforming growth factor beta (TGFbeta1), basic fibroblast growth factor (bFGF), markers for nonspecific inflammatory process (interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP)) and their putative correlation with advanced glycation end-products relative to diabetes compensation in patients with ischemic heart disease (IHD).
Materials and Methods.
87 patients with IHD were enrolled in this study. All subjects underwent standard clinical examination, including laboratory assessment of glycemic parameters, lipid panel and renal function, with echocardiography, supplemented with coronary angiography. Analyses for study parameters were performed on samples obtained from aorta and, separately, from cubital vein during coronary angiography.
Results.
Diabetes mellitus in patients with IHD is firmly associated with TGFbeta1, IL-6 and CRP elevation in both arterial and venous plasma. TGFbeta1 positively correlates with lipid profile parameters. Plasma concentration of inflammatory markers and advanced glycation end-products positively correlates with the extent of coronary lesions in relation to the presence of diabetes mellitus.
Conclusion.
Our data suggests the interplay between connective tissue growth factors and lipid metabolism in the atherosclerotic process.

fibroblast growth factors, diabetes mellitus, ischemic heart diseases

1. Flavell SJ, Hou TZ, Lax S, Filer AD, Salmon M, Buckley CD. Fibroblasts as novel therapeutic targets in chronic inflammation. British Journal of Pharmacology. 2008;153(S1):S241-S246. DOI: http://dx.doi.org/10.1038/sj.bjp.0707487

2. Yun Y-R, Won JE, Jeon E, Lee S, Kang W, Jo H, et al. Fibroblast Growth Factors: Biology, Function, and Application for Tissue Regeneration. Journal of Tissue Engineering. 2010 January 1, 2010;1(1). DOI: http://dx.doi.org/10.4061/2010/218142

3. Шурыгина ИА, Шурыгин МГ, Аюшинова НИ, Каня ОВ. Фибробласты и их роль в развитии соединительной ткани. Сибирский медицинский журнал.2012;110(3):8-12. [Shurygina IA, Shurygin MG, Ayushinova NI, Kanya OV. Fibroblasts and their role in the development of connective tissue. Sibirskiy meditsinskiy zhurnal. 2012;110(3):8-12]

4. Keeley EC, Mehrad B, Strieter RM. Fibrocytes: Bringing new insights into mechanisms of inflammation and fibrosis. The international journal of biochemistry & cell biology. 2010 Apr;42(4): 535-542. DOI: http://dx.doi.org/10.1016/j.biocel.2009.10.014

5. Chesney J, Metz C, Stavitsky AB, Bacher M, Bucala R. Regulated production of type I collagen and inflammatory cytokines by peripheral blood fibrocytes. Journal of immunology. 1998 Jan 1;160(1):419-425.

6. Hartlapp I, Abe R, Saeed RW, Peng T, Voelter W, Bucala R, et al. Fibrocytes induce an angiogenic phenotype in cultured endothelial cells and promote angiogenesis in vivo. FASEB journal. 2001 Oct;15(12):2215-2224. DOI: http://dx.doi.org/10.1096/fj.01-0049com

7. Conway EM, Collen D, Carmeliet P. Molecular mechanisms of blood vessel growth. Cardiovascular Research. 2001 February 16, 2001;49(3):507-521. DOI: http://dx.doi.org/10.1016/S0008-6363(00)00281-9

8. Шурыгин МГ, Шурыгина ИА. Фактор роста фибробластов как стимулятор ангиогенеза при инфаркте миокарда. Бюллетень Сибирского отделения Российской академии медицинских наук. 2010;30(6):89-92. [Shurygin MG, Shurygina IA. Fibroblast growth factor as angiogenesis stimulator at myocardial infarction. Bulletin of the Siberian Branch of the Russian Academy of Medical Sciences. 2010;30(6):89-92.]

9. Presta M, Dell’Era P, Mitola S, Moroni E, Ronca R, Rusnati M. Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine & growth factor reviews. 2005;16(2):159-178. DOI: http://dx.doi.org/10.1016/j.cytogfr.2005.01.004

10. Mignatti P, Rifkin DB. Biology and biochemistry of proteinases in tumor invasion. Physiological Reviews. 1993 January 1, 1993;73(1):161-195.

11. Klein S, Giancotti FG, Presta M, Albelda SM, Buck CA, Rifkin DB. Basic fibroblast growth factor modulates integrin expression in microvascular endothelial cells. Molecular Biology of the Cell. 1993 October 1, 1993;4(10):973-982. DOI: http://dx.doi.org/10.1091/mbc.4.10.973

12. Alexandraki K, Piperi C, Kalofoutis C, Singh J, Alaveras A, Kalofoutis A. Inflammatory Process in Type 2 Diabetes. Annals of the New York Academy of Sciences. 2006;1084(1):89-117. DOI: http://dx.doi.org/10.1196/annals.1372.039

13. Подгребельный АН, Смирнова ОМ, Дедов ИИ. Роль фибробластов в развитии сахарного диабета и его осложнений. Проблемы эндокринологии. 2005;51(2):14-22. [Podgrebel'nyy AN, Smirnova OM, Dedov II. Rol' fibroblastov v razvitii sakharnogo diabeta i ego oslozhneniy. Problemy endokrinologii. 2005;51(2):14-22.]

14. Portero-Otín M, Pamplona R, Bellmunt MJ, Ruiz MC, Prat J, Salvayre R, et al. Advanced Glycation End Product Precursors Impair Epidermal Growth Factor Receptor Signaling. Diabetes. 2002 May 1, 2002;51(5):1535-1542. DOI: http://dx.doi.org/10.2337/diabetes.51.5.1535

15. Bellini A, Mattoli S. The role of the fibrocyte, a bone marrow-derived mesenchymal progenitor, in reactive and reparative fibroses. Laboratory investigation; a journal of technical methods and pathology. 2007 Sep;87(9):858-870. DOI: http://dx.doi.org/10.1038/labinvest.3700654

16. Rydén L, Standl E, Bartnik M, Van den Berghe G, Betteridge J, de Boer M-J, et al. Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary: The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). European heart journal. 2007 January 1, 2007;28(1):88-136. DOI: http://dx.doi.org/10.1093/eurheartj/ehl260

17. A Comparison of Recombinant Hirudin with Heparin for the Treatment of Acute Coronary Syndromes. New England Journal of Medicine. 1996;335(11):775-782. DOI: http://dx.doi.org/10.1056/NEJM199609123351103

18. King DE, Mainous AG, Buchanan TA, Pearson WS. C-Reactive Protein and Glycemic Control in Adults With Diabetes. Diabetes Care. 2003 May 1, 2003;26(5):1535-1539. DOI: http://dx.doi.org/10.2337/diacare.26.5.1535

19. Bartnik M, Rydén L, Ferrari R, Malmberg K, Pyörälä K, Simoons M, et al. The prevalence of abnormal glucose regulation in patients with coronary artery disease across Europe: The Euro Heart Survey on diabetes and the heart. European heart journal. 2004 November 1, 2004;25(21):1880-1890. DOI: http://dx.doi.org/10.1016/j.ehj.2004.07.027

20. Барбараш ОЛ, Авраменко ОЕ, Осокина АВ, Сумин АН, Веремеев АВ. Роль провоспалительных факторов в оценке прогноза больных с прогрессирующей стенокардией в сочетании с сахарным диабетом 2 типа. Сахарный диабет. 2012;4:39–45. [Barbarash OL, Avramenko OE, Osokina AV, Sumin AN, Veremeev A. Prognostic significance of proinflammatory factors in patients with progressive angina pectoris and type 2 diabetes mellitus. Diabetes mellitus. 2012;4:39-45.]

21. Подгребельный АН, Смирнова ОМ, Дедов ИИ, Ильин АВ, Никанкина ЛВ, Котельников МВ, Чернядьева ЮИ, Сунцов ЮИ. Атеросклероз и факторы роста (TGFb и bFGF) у пациентов с сахарным диабетом типа 2. Сахарный диабет. 2005;1:26-29. [Podgrebel'nyj A.N., Smirnova O.M., Dedov I.I., Il’in A.V., Nikankina L.V., Kotel'nikov M.V., Chernjad'eva Ju.I., Suntsov Y.I. Ateroskleroz i faktory rosta (TGFBL i BFGF) u patsientov s sakharnym diabetom tipa 2. Diabetes mellitus. 2005;1:26-29.]

22. Celec P, Hodosy J, Jáni P, Janega P, Kúdela M, Kalousová M, et al. Advanced glycation end products in myocardial reperfusion injury. Heart Vessels. 2012 2012/03/01;27(2):208-215. DOI: http://dx.doi.org/10.1007/s00380-011-0147-z

23. van Heerebeek L, Hamdani N, Handoko ML, Falcao-Pires I, Musters RJ, Kupreishvili K, et al. Diastolic Stiffness of the Failing Diabetic Heart: Importance of Fibrosis, Advanced Glycation End Products, and Myocyte Resting Tension. Circulation. 2008 January 1, 2008;117(1):43-51. DOI: http://dx.doi.org/10.1161/CIRCULATIONAHA.107.728550