Cardioprotection of exogenous erythropoietin in mice with ligature-induced aortic stenosis: effects on maladaptive cardiac hypertrophy

• Autorzy: Zheng L. , Xu J. , Qiu W. , Liu X. , Zhao C.-M. , Chen D. , Chen Y.
• Języki publikacji: EN

Abstrakty

EN

Pre-operative treatment with recombinant human erythropoietin may improve aortic stenosis patients' condition, including anemia and/or cardiac dysfunction, for subjecting to aortic valve replacement. In this study, we tested this hypothesis in a mouse model of aortic stenosis. Adult male mice were subjected to either aortic stenosis created by aortic ligature or sham operation. Aortic stenosis for 4 weeks caused cardiac hypertrophy, pulmonary congestion and left ventricular dysfunction. It was associated with increased levels of tumor necrosis factor-a in serum and myocardium, and reduced levels of interleukin-10 in myocardium but not in serum. Mytocyte apoptosis rate, level of cleaved caspase 3, activity of nuclear factor-B and expression of p38-MAPK pathway were also elevated. Erythropoietin treatment increased hematocrit but did not prevent the development of cardiac hypertrophy. It, however, reduced the apoptosis, prevented the increases in tumor necrosis factor-, nuclear factor-B activation and phosphorylation of p38, and attenuated the increases in lung weight, the decreases in LVEF and LVFS, and the increases in LVDd and LVDs. In conclusion recombinant human erythropoietin has cardioprotective effects in maladaptive cardiac hypertrophy by inhibiting nuclear factor-B activation, phosphorylation of p38-MAPK pathway, and production of tumor necrosis factor-, together leading to a reduced apoptosis.

Słowa kluczowe

EN

cardioprotection; exogenous erythropoietin; mice; mouse; ligature; aortic stenosis; cardiac hypertrophy; erythropoietin; heart failure; inflammation; tumour necrosis factor-alpha; apoptosis

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2010
• Tom: 61
• Numer: 1
• Opis fizyczny: p.13-20,fig.,ref.

Twórcy

autor

Zheng L.

• The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

autor

Xu J.

autor

Qiu W.

autor

Liu X.

autor

Zhao C.-M.

autor

Chen D.

autor

Chen Y.

Bibliografia

• Lindroos M, Kupari M, Heikkila J, et al. Prevanlence of aortic valve abnormalities in the elderly: an echocardiographic study of a random population sample. J Am Coll Cardiol 1993; 21: 1220-1225.
• Martinez MW, Nishimura RA. Approach to the patient with aortic stenosis and low ejection fraction. Curr Cardiol Rep 2006; 8: 90-95.
• Grimard BH, Larson JM. Aortic stenosis: diagnosis and treatment. Am Fam Physician 2008; 78: 717-724.
• Ding WH, Lam YY, Pepper JR, et al. Early and long-term survival after aortic valve replacement in septuagenarians and octogenarians with severe aortic stenosis. Int J Cardiol 2009; doi:10.1016/j.ijcard.2008.11.126
• Maiese K, Li F, Chong ZZ. New avenues of exploration for erythropoietin. JAMA 2005; 293: 90-95.
• Parsa CJ, Kim J, Riel RU, Pascal LS, et al. Cardioprotective effects of erythropoietin in the reperfused ischemic heart: a potential role for cardiac fibroblasts. J Biol Chem 2004; 279: 20655-20662.
• Ruifrok WP, de Boer RA, Westenbrink BD, et al. Erythropoietin in cardiac disease: new features of an old drug. Eur J Pharmacol 2008; 585: 270-277.
• Asaumi Y, Kagaya Y, Takeda M, et al. Protective role of endogenous erythropoietin system in nonhematopoietic cells against pressure overload-induced left ventricular dysfunction in mice. Circulation 2007; 115: 2022-2032.
• Brines M, Cerami A. Discovering erythropoietin's extra-hematopoietic functions: biology and clinical promise. Kidney Int 2006; 70: 246-250.
• Beholz S, Liu J, Thoelke R, et al. Use of despopressin and erythropoietin in an anaemic Jehovah's Witness patient with severely impaired coagulation capacity undergoing stentless aortic valve replacement. Perfusion 2001; 16: 485-489.
• Cheung EH, Sutton SW, Marcel R. Aortic valve replacement in a dialysis dependent Jehovah' Witness: successful use of a minicircuit, microplegia and multimodality blood conservation technique. Proc (Bayl Univ Med Cent) 2007; 20: 32-35.
• Rajamannan NM. Low-density lipoprotein and aortic stenosis. Heart 2008; 94: 1111-1112.
• Molina EJ, Palma J, Gupta D, et al. Improvement in hemodynamic performance, exercise capacity, inflammatory profile, and left ventricular reverse remodeling after intracoronary delivery of mesenchymal stem cells in experimental model of pressure overload hypertrophy. J Thorac Cardiovasc Sury 2008; 135: 292-299.
• Li Y, Takemura G, Okada H, et al. Reduction of inflammatory cytokine expression and oxidative damage by erythropoietin in chronic heart failure. Cardiovasc Res 2006; 71: 684-694.
• Xu Q, Lekgabe ED, Gao XM, et al. Endogenous relaxin does not affect chronic pressure overload-induced cardiac hypertrophy and fibrosis. Endocrinology 2008; 149: 476-482.
• Li J, Wu M, Que L, et al. 17beta-estradiol attenuates cardiac dysfunction and decreases NF-kappaB binding activity in mechanically stretched rat hearts. Steroids 2008; 73: 720-726.
• Sun M, Chen M, Dawood F, et al. Tumor necrosis factor-alpha mediates cardiac remodeling and ventricular dysfunction after pressure overload state. Circulation 2007; 115: 1398-1407.
• Bozkurt B, Torre-Amione G, Warren MS, et al. Results of targeted anti-tumor necrosis factor therapy with etanercept (ENBREL) in patients with advanced heart failure. Circulation 2001; 103: 1044-1047.
• Kaur K, Sharma AK, Singal PK. Significance of changes in TNF-alpha and IL-10 levels in the progression of heart failure subsequent to myocardial infarction. Am J Physiol Heart Circ Physiol 2006; 291: H106-H113.
• Higuchi Y, Chan TO, Brown MA, et al. Cardioprotection afforded by NF-kappaB ablation is associated with activation of Akt in mice overexpression TNF-alpha. Am J Physiol Heart Circ Physiol 2006; 290: H590-H598.
• Selvetella G, Hirsch E, Notte A, et al. Adaptive and maladaptive hypertrophic pathways: points of convergence and divergence. Cardiovasc Res 2004; 63: 373-380.
• Heymans S, Hirsch E, Anker SD, et al. Inflammation as a therapeutic target in heart failure? A scientific statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2009; 11: 119-129.
• Shaw SM, Shah MK, Williams SG, Fildes JE. Immunological mechanisms of pentoxifylline in chronic heart failure. Eur J Heart Fail 2009; 11: 113-118.
• Hilfiker-Kleiner D, Landmesser U, Drexler H. Molecular mechanisms in heart failure focus on cardiac hypertrophy, inflammation, angiogenesis, and apoptosis. J Am Coll Cardiol 2006; 48: A56-A66.
• Louhelainen M, Merasto S, Finckenberg P, et al. Effects of calcium sensitizer OR-1986 ona cardiovascular mortality and myocardial remodelling in hypertensive Dahl/Rapp rats. J Physiol Pharmacol 2009; 60: 41-47.
• Kiriazis H, Wang K, Xu Q, et al. Knockout of beta(1)- and beta(2)-adrenoceptors attenuates pressure overload-induced cardiac hypertrophy and fibrosis. Br J Pharmacol 2008; 153: 684-692.
• Heather LC, Catchpole AF, Stuckey DJ, et al. Isoproterenol induces in vivo functional and metabolic abnormalities: similar to those found in the infarcted rat heart. J Physiol Pharmacol 2009; 60: 31-39.
• Penna C, Abbadessa G, Mancardi D, et al. Synergistic effects against post-ischemic cardiac dysfunction by sub-chronic nandrolone pretreatment and postconditioning: role of beta2-adrenoceptor. J Physiol Pharmacol 2008; 59: 645-659.