Russian Heart Failure Journal 2011year Influence of therapy by selective beta1-blocker bisoprolol and selective beta1-blocker with NO-modeling nebivolol on myocardial collagen balance at CHF patients

To access this material please log in or register

Register Authorize

Influence of therapy by selective beta1-blocker bisoprolol and selective beta1-blocker with NO-modeling nebivolol on myocardial collagen balance at CHF patients

Zhubrina E. S., Ovchinnikov A. G., Seredina E. M., Masenko V. P., Ageyev F. T.
Federal State Budgetary Institution, “Russian Cardiology Research and Production Complex” of the RF Ministry of Health Care, 3rd Cherepkovskaya 15a, Moscow 121552

Keywords: beta-adrenergic blocker agents, collagen exchange, CHF

DOI: 10.18087/ rhfj.2011.5.1570

Relevancy. Imbalance in myocardial collagen plays an important role in physiopathology of both systolic and diastolic heart failure. Objective. Evaluation of β1-adrenergic blocker agent of bisoprolol and β1-adrenergic blocker agent with NO-modeling properties of nebivolol influence on marker balance content of type I collagen. Materials and methods. 67 patients with stable CHF II–III FC, with reduced and safe systolic function of left ventricle, being at standard therapy, were randomized by groups treated by bisoprolol (n=35) or nebivolol (n=32). Initially and 6 months later after a therapy the patents were evaluated for clinical and haemodynamic status as well as for the level of C-terminal collagen propeptide of the type I (СICP), collagen synthesis marker of the type I and C-terminal collagen telopeptide, the type I (CITP), collagen deterioration marker of the type I, in blood serum. Results. Subgroups of CHF patients with safe and reduced (<50 %) function of left ventricle did not authentically differ by initial level of collagen change markers of the type I. Notwithstanding that CHF patients therapy by bisoprolol and nebivolol in equivalent doses was accompanied by comparable authentic improvement of clinical and haemodynamic status, the nebivolol group only showed the authentic reduce of CICP level, including patients both with diastolic and systolic CHF, by 12.8 and 13.1 % accordingly, as well as authentic reduce of CICP / CITP ratio (all р<0.05). Neither nebivolol group nor bisoprolol group showed authentic dynamic of CITP content. Thus the results of this research showed that despite comparable clinical efficiency of both specimens, nebivolol only demonstrated an authentic influence on collagen exchange for CHF patients both with safe and reduced function of left ventricle, relocating it towards collagen synthesis reduction of the type I.
  1. Alberts B, Bray D, Lewis J, et al. Molecular Biology of the Cell. 3rd ed. New York, NY: Garland Publishing; 1994.
  2. Streeter DD Jr, Spotnitz HM, Patel DP, Ross J Jr, Sonnenblick E. H. Fiber orientation in the canine left ventricle during diastole and systole. Circ Res. 1969;24 (3):339–347.
  3. Covell JW. Factors influencing diastolic function: possible role of the extracellular matrix. Circulation. 1990;81 (2 Suppl):III155–158.
  4. Fedak P. W, Altamentova S. M, Weisel R. D, et al. Matrix remodeling in experimental and human heart failure: a possible regulatory role for TIMP-3. Am J Physiol Heart Circ Physiol. 2003;284 (2):H626–634.
  5. Heymans S, Luttun A, Nuyens D et al. Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure. Nat Med. 1999;5 (10):1135–1142.
  6. Ichihara S, Senbonmatsu T, Price E Jr et al. Targeted deletion of angiotensin II type 2 receptor caused cardiac rupture after acute myocardial infarction. Circulation. 2002 Oct 22;106 (17):2244–2249.
  7. Kanoupakis EM, Manios EG, Kallergis EM et al. Serum markers of collagen turnover predict future shocks in implantable cardioverter-defibrillator recipients with dilated cardiomyopathy on optimal treatment. J Am Coll Cardiol. 2010;55 (24):2753–2759.
  8. Klappacher G, Franzen P, Haab D et al. Measuring extracellular matrix turnover in the serum of patients with idiopathic or ischemic dilated cardio­myopathy and impact on diagnosis and prognosis. Am J Cardiol. 1995;75 (14):913–918.
  9. Zannad F, Alla F, Dousset B et al. Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure. Insights from Randomized Aldactone Evaluation Study (RALES). Circulation. 2000;102 (22):2700–2706.
  10. Spinale FG. Myocardial matrix remodeling and matrix metalloproteinases: influence on cardiac form and function. Physiol Rev. 2007;87 (4):1285–1342.
  11. Jugdutt BI. Ventricular remodeling after infarction and the extracellular collagen matrix: when is enough enough? Circulation. 2003;108 (11):1395–1403.
  12. Risteli J, Elomaa I, Niemi S et al. Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen: a new serum marker of bone collagen degradation. Clin Chem. 1993;39 (4):635–640.
  13. Melkko J, Niemi S, Risteli L, Risteli J. Radioimmunoassay of the carboxyterminal propeptide of human type I procollagen. Clin Chem. 1990;36 (7):1328–1332.
  14. Querejeta R, Varo N, Lopez B et al. Serum carboxy-terminal propeptide of procollagen type I is a marker of myocardial fibrosis in hypertensive heart disease. Circulation. 2000;101 (14):1729–1735.
  15. Barasch Е, Gottdiener JS, Aurigemma G et al. Myocardial matrix remode­ling and the matrix metalloproteinases: influence on cardiac form and function. Physiol Rev. 2007;87 (4):1285–1342.
  16. Frustaci A, Chimenti C, Bellocci F et al. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation. 1997;96 (4):1180–1184.
  17. Kallergis ЕМ, Manios EG, Kanoupakis EM et al. Extracellular matrix alterations in patients with paroxysmal and persistent atrial fibrillation: biochemical assessment of collagen type-I turnover. J Am Coll Cardiol. 2008;52 (3):211–215.
  18. Gunja-Smith Z, Morales AR, Romanelli R, Woessner JF Jr. Remodeling of human myocardial collagen in idiopathic dilated cardiomyopathy. Role of metalloproteinases and pyridinoline cross-links. Am J Pathol. 1996;148 (5):1639–1648.
  19. Dorn GW. Adrenergic pathways and left ventricular remodeling. J Card Fail. 2002;8 (6 Suppl):S370–373.
  20. Pick R, Jalil JE, Janicki JS, Weber KT. The fibrillar nature and structure of isoproterenol-induced myocardial fibrosis in the rat. Am J Pathol. 1989;134 (2):365–371.
  21. Akiyama-Uchida Y, Ashizawa N, Ohtsuru A et al. Norepinephrine enhan­ces fibrosis mediated by TGF-beta in cardiac fibroblasts. Hypertension. 2002;40 (2):148–154.
  22. Barth W, Deten A, Bauer M et al. Differential remodeling of the left and right heart after norepinephrine treatment in rats: studies on cytokines and collagen. J Mol Cell Cardiol. 2000;32 (2):273–284.
  23. Bhambi B, Eghbali M. Effect of norepinephrine on myocardial collagen gene expression and response of cardiac fibroblasts after norepinephrine treatment. Am J Pathol. 1991;139 (5):1131–1142.
  24. Grimm D, Huber M, Jabusch H. C, et al. Extracellular matrix proteins in cardiac fibroblasts derived from rat hearts with chronic pressure overload: effects of beta-receptor blockade. J Mol Cell Cardiol. 2001;33 (3):487–501.
  25. Myers PR, Tanner MA. Vascular endothelial cell regulation of extracellular matrix collagen: role of nitric oxide. Arterioscler Thromb Vasc Biol. 1998;18 (5):717–722.
  26. Kolpakov V, Gordon D, Kulik TJ. Nitric oxide-generating compounds inhibit total protein and collagen synthesis in cultured vascular smooth muscle cells. Circ Res. 1995;76 (2):305–309.
  27. Rizvi M, Myers P. Nitric oxide modulates basal and endothelin-induced coronary artery vascular smooth muscle cell proliferation and collagen le­vels. J Mol Cell Cardiol. 1997;29 (7):1779–1789.
  28. Westermann D, Riad A, Richter U et al. Enhancement of the endothelial NO synthase attenuates experimental diastolic heart failure. Basic Res Cardiol. 2009;104 (5):499–509.
  29. Sorrentino SA, Doerries C, Mohmand W et al. Abstract 1869: Effect of Nebivolol vs. Metoprolol on Endothelial Function, Endothelial Progenitor Cell Mobilization and Left Ventricular Remodeling and Dysfunction Early After Myocardial Infarction. Circulation. 2006;114:II.
Zhubrina E. S., Ovchinnikov A. G., Seredina E. M. et al. Influence of therapy by selective beta1-blocker bisoprolol and selective beta1-blocker with NO-modeling nebivolol on myocardial collagen balance at CHF patients. Russian Heart Failure Journal. 2011;12(5):260-266.

To access this material please log in or register

Register Authorize
Ru En