慢性心力衰竭机制与免疫的相关性-现代医学

慢性心力衰竭机制与免疫的相关性

单位：1. 贵州医科大学研究生院, 贵州贵阳 550025;
2. 贵州医科大学附属医院急诊科, 贵州贵阳 550025;
3. 贵州医科大学附属医院急诊科, 贵州贵阳 550025

关键词：心力衰竭免疫激活 Toll样受体(TLRs) 白细胞介素肿瘤坏死因子-α

分类号：R541.7

出版年·卷·期（页码）：2020·48·第一期（135-140）

摘要：

心力衰竭（HF）指的是一种心脏功能不足的状态，由于心脏的收缩功能和（或）舒张功能发生障碍，不能将静脉回心血量充分排出心脏，导致静脉系统血液淤积，动脉系统血液灌注不足，从而引起心脏循环障碍症候群。HF是全球人类发病和死亡率高的主要原因。目前的研究工作集中在寻找新的机制和信号传导途径。免疫激活，炎症，氧化应激，线粒体生物学的改变被认为是该过程中的重要病理生理事件。我们对于慢性心衰的免疫相关机制进行概述总结。

Heart failure (HF) refers to a state of insufficient heart function. Due to the systolic function and/or diastolic function of the heart, it is impossible to completely discharge the venous return blood to the heart, resulting in venous system blood accumulation, arteries. Insufficient blood perfusion in the system causes cardiac dysfunction syndrome. Heart failure (HF) is the leading cause of morbidity and mortality worldwide. Current research efforts focus on finding new mechanisms and signaling pathways. Immune activation, inflammation, oxidative stress, and changes in mitochondrial bioenergetics are thought to be important pathophysiological events in the process. We provide an overview of the immune-related mechanisms of chronic heart failure.

参考文献：

[1] WAGNER K B,FELIX S B,RIAD A.Innate immune receptors in heart failure:side effect or potential therapeutic target[J].World J Cardiol.2014,6(8):791-801.
[2] MANN D L.The emerging role of innate immunity in the heart and vascular system:for whom the cell tolls[J].Circ Res.2011,108(9):1133-1145.
[3] HENNESSY E J,PARKER A E,O'NEILL L A.Targeting toll-like recep-tors:emerging therapeutics[J].Nat Rev Drug Discov.2010,9(4):293-307.
[4] ZHU X,ZHAO H,GRAVELINE A R,et al.MyD88 and NOS2 are essential for toll-like receptor 4-mediated survival effect in cardiomyocytes[J].Am J Physiol Heart Circ Physiol.2006,291(4):H1900-1909.
[5] CHAO W.Toll-like receptor signaling:a critical modulator of cell survival and ischemic injury in the heart[J].Am J Physiol Heart Circ Physiol.2009,296(1):H1-12.
[6] FUKUNAGE T,SOEJIMA T,Soejima H,et al.Expression of interferon-gamma and interleukin-4 production in CD4 T cells in patients with chronic heart failure[J].Heart Vessel.2007,22(3):178-183.
[7] SATOH S,OYAMA J,et al.Increased productivity of tumor necrosis factor-alpha in helper T cells in patients with systolic heart failure[J].Int J Cardiol.2006,111(3):405-412.
[8] KAMANAKA M,O'CONNOR W Jr,et al.Memory/effector (CD45RB (lo)) CD4 T cells are controlled directly by IL-10 and cause IL-22-dependent intes-tinal pathology[J].Exp Med.2011,208(5):1027-1040.
[9] LIANG H E,REINHARDT R L.Divergent expression patterns of IL-4 and IL-13 define unique functions in allergic immunity[J].Nat Immunol.2011,13(1):58-66.
[10] LAROUMANIE F,DOUIN-ECHINARD V,et al.CD4+T cells promote the transition from hypertro-phy to heart failure during chronic pressure overload[J].Circulation.2014,129(21):2111-2124.
[11] HOFMANN U,BEYERSDORF N,et al.Activation of CD4+T lymphocytes improves wound healing and survival after experimental myocar-dial infarction in mice[J].Circulation.2012,125(13):1652-1663.
[12] SWIRSKI F K,NAHRENDORF M.Leukocyte behavior in atherosclero-sis,myocardial infarction,and heart failure[J].Science.2013,339(6116):161-166.
[13] LIBBY P,NAHRENDORF M,SWIRSKI F K.Leukocytes link local and systemic inflammation in Is Chemic Cardiovascular Disease:An Expanded "Cardiovascular Continuum"[J].Am Coll Cardiol.2016,67(9):1091-1103.
[14] OKAMOTO N,NOMA T,et al.Prognostic value of circulating regulatory T cells for worsening heart failure in heart failure patients with reduced ejection fraction[J].Int Heart,2014,55(3):271-277.
[15] FRIELER R A,MORTENSEN R M.Immune cell and other noncardiomyocyte regulation of cardiac hypertrophy and remod-eling[J].Circulation.2015,131(11):1019-1030.
[16] MULLER-WERDAN U,BUERKE M,et al.Septic cardiomyopathy-A not yet discovered cardiomyopathy[J].Exp Clin Cardiol.2006,11(3):226-236.
[17] KUMAR A,THOTA V.Tumor necrosis factor alpha and interleukin 1beta are responsible for in vitro myocardial cell depression induced by human septic shock serum[J].Exp Med.1996,183(3):949-958.
[18] VAN TASSELL B W,ARENA R A,TOLDO S,et al.Enhanced interleukin-1 activity contributes to exercise intolerance in patients with systolic heart failure[J].PLoS One.2012,7(3):e33438.
[19] VAN TASSELL B W,SEROPIANI M,TOLDO S,et al.Interleukin-1beta induces a reversible cardiomyopathy in the mouse[J].Inflamm Res.2013,62(7):637-640.
[20] ALEKSOVA A,BELTRAMI A P,CARRIERE C,et al.Interleukin-1beta levels predict long-term mortality and need for heart transplantation in ambula-tory patients affected by idiopathic dilated cardiomyopathy[J].Oncotarget.2017,8(15):25131-25140.
[21] HILFIKER-KLEINER D,SHUKLA P,KLEIN G,et al.Continuous glycoprotein-130-mediated signal transducer and activator of transcription-3 activation promotes inflammation,left ventricular rupture,and adverse outcome in subacute myocar-dial infarction[J].Circulation.2010,122(2):145-155.
[22] SWERDLOW D I,HOLMES M V,KUCHENBAECKER K B,et al.The interleukin-6 receptor as a target for prevention of coronary heart disease:a mendelian randomisation analysis[J].Lancet.2012,379(9822):1214-1224.
[23] FISCHER P,HILFIKER-KLEINER D.Role of gp130-mediated signalling pathways in the heart and its impact on potential therapeutic as-pects[J].Br J Pharmacol.2008,153(Suppl 1):S414-427.
[24] FISCHER P,HILFIKER-KLEINER D.Survival pathways in hypertrophy and heart failure:the gp130-STAT axis[J].Basic Res Cardiol.2007,102(5):393-411.
[25] SMART N,MOJET M H,LATCHMAN D S,et al.IL-6 induces PI 3-kinase and nitric oxide-dependent protection and preserves mitochondrial function in cardiomyocytes[J].Cardiovasc Res.2006,69(1):164-177.
[26] RITSCHEL V N,SELJEFLOT I,ARNESEN H,et al.IL-6 signalling in patients with acute ST-elevation myocardial infarction[J].Results Immunol.2014,(4):8-13.
[27] KAUR K,SHARMA A K,SINGAL P K.Significance of changes in TNF-alpha and IL-10 levels in the progression of heart failure subse-quent to myocardial infarction[J].Am J Physiol Heart Circ Physiol.2006,291(1):H106-113.
[28] STUMPF C,LEHNER C,YILMAZ A,et al.Decrease of serum levels of the anti-inflammatory cytokine interleukin-10 in patients with advanced chronic heart failure[J].Clin Sci (Lond).2003,105(1):45-50.
[29] AMIR O,ROGOWSKI O,DAVID M,et al.Circulating interleukin-10:association with higher mortality in systolic heart failure patients with elevated tumor necrosis factor-alpha[J].Isr Med Assoc J:IMAJ.2010,12(3):158-162.
[30] LIUZZO G,TROTTA F,PEDICINO D.Interleukin-17 in atherosclerosis and cardiovascular disease:the good,the bad,and the unknown[J].Eur Heart.2013,(8):556-559.
[31] LAFRAMBOISE W A,SCALISE D,STOODLEY P,et al.Cardiac fibroblasts influence cardiomyocyte phenotype in vitro[J].Am J Phys Cell Phys.2007;292(5),C1799-1808.
[32] LI XF,PAN D,ZHANG WL,et al.Association of NT-proBNP and interleukin-17 levels with heart failure in elderly patients[J].Genet Mol Res.2016,15(2).
[33] MORITA M,YANO S,YAMAGUCHI T,et al.Advanced glycation end products-induced reactive oxygen species genera-tion is partly through NF-kappa B activation in human aortic endothelial cells[J].Diabetes Complicat.2013,27(1):11-15.
[34] HUSBERG C,NYGARD S,FINSEN A V,et al.Cytokine expression profiling of the myocardium reveals a role for CX3CL1(fractalkine) in heart failure[J].Mol Cell Cardiol.2008,45(2):261-269.
[35] KOLLER L,BLUM S,KORPAK M,et al.Predictive power of the fractalkine receptor CX3CR1 on CD4 T cells in patients with chronic heart failure[J].Int J Cardiol.2014,171(1):96-79.
[36] FRANTZ S,FRACCAROLLO D,WAGNER H,et al.Sustained activation of nuclear factor kappa B and acti-vator protein 1 in chronic heart failure[J].Cardiovasc Res.2003,57(3):749-756.
[37] GRABELLUS F,LEVKAU B,SOKOLL A,et al.Reversible activation of nuclear factor-kappaB in human end-stage heart failure after left ventricular mechanical support[J].Cardiovasc Res.2002,53(1):124-130.
[38] MAEKAWA Y,ANZAI T,YOSHIKAWA T,et al.Effect of granulocyte-macrophage colony-stimulating factor inducer on left ventricular remodeling after acute myocardial infarction[J].Am Coll Cardiol.2004,44(7):1510-1520.
[39] HAYASAKI T,KAIKITA K,OKUMA T,et al.CC chemokine receptor-2 deficiency attenuates oxidative stress and infarct size caused by myocardial ischemia-reperfusion in mice[J].Circ 2006,70(3):342-351.
[40] HAYASHIDANI S,TSUTSUI H,SHIOMI T,et al.Anti-monocyte chemoattractant protein-1 gene therapy attenuates left ventricular remodeling and failure after experimental myocardial infarction[J].Circulation.2003;108(17):2134-2140.
[41] KOHNO T,ANZAI T,NAITO K,et al.Angiotensin-receptor blockade reduces border zone myocar-dial monocyte chemoattractant protein-1 expression and macro-phage infiltration in post-infarction ventricular remodeling[J].Circ 2008,72(10):1685-1692.
[42] HORTON J W,MAASS D,WHITE J,et al.Nitric oxide modulation of TNF-alpha-induced cardiac contractile dysfunction is concentration dependent[J].Am J Physiol Heart Circ Physiol.2000,278(6):H1955-1965.
[43] HAMID T,GU Y,ORTINES R V,et al.Divergent tumor necrosis factor receptor-related remodeling responses in heart failure:role of nuclear factor-kappaB and in-flammatory activation.[J].Circulation.2009,119(10):1386-1397.
[44] AWAD A E,KANDALAM V,CHAKRABARTI S,et al.Tumor necrosis factor induces matrix metallo-proteinases in cardiomyocytes and cardiofibroblasts differentially via superoxide production in a PI3Kgamma-dependent manner[J].Am J Phys Cell Phys.2010,298(3):C679-692.
[45] KAO Y H,CHEN Y C,CHENG C C,et al.Tumor necrosis factor-alpha decreases sarcoplasmic reticulum Ca²⁺-ATPase expressions via the promoter methylation in cardiomyocytes[J].Crit Care Med.2010,38(1):217-222.
[46] DIBBS Z I,DIWAN A,NEMOTO S,et al.Targeted overexpression of transmembrane tumor necrosis factor provokes a concentric cardiac hypertrophic phenotype[J].Circulation.2003,108(8):1002-1008.
[47] KUBOTA T,BOUNOUTAS G S,MIYAGISHIMA M,et al.Soluble tumor necrosis factor receptor abrogates myocardial inflammation but not hypertrophy in cytokine-induced cardiomyopathy[J].Circulation.2000,101(21):2518-2525.
[48] GULICK T,CHUNG M K,PIEPER S J,et al.Interleukin 1 and tumor necrosis factor inhibit cardiac myocyte beta-adrenergic responsiveness[J].Proc Natl Acad Sci U S A.1989,86(17):6753-6757.
[49] CHUNG M K,GULICK T S,ROTONDO R E,et al.Mechanism of cytokine inhibition of beta-adrenergic agonist stim-ulation of cyclic AMP in rat cardiac myocytes.Impairment of signal transduction.[J].Circ Res.1990,67(3):753-763.
[50] LEE S H,CHEN Y C,CHEN Y J,et al.Tumor necrosis factor-alpha alters calcium handling and increases arrhythmogenesis of pulmonary vein cardiomyocytes.Life Sci.2007,80(19):1806-1815.
[51] KUBOTA T,MIYAGISHIMA M,ALVAREZ R J,et al.Expression of proinflammatory cytokines in the failing human heart:comparison of recent-onset and end-stage congestive heart failure[J].Heart Lung Transplant.2000,19(9):819-824.
[52] BELOSJOROW S,BOLLE I,DUSCHIN A,et al.TNF-alpha antibodies are as effective as ischemic preconditioning in reducing infarct size in rabbits[J].Am J Physiol Heart Circ Physiol.2003,284(3):H927-930.
[53] GAO C,LIU Y,YU Q,et al.TNF-alpha antagonism ameliorates myocardial ischemia-reperfusion injury in mice by upregulating adiponectin[J].Am J Physiol Heart Circ Physiol.2015,308(12):H1583-591.
[54] BLANCO-COLIO L M.TWEAK/Fn14 axis:a promising target for the treatment of cardiovascular diseases[J].Front Immunol.2014,5:3.
[55] FRANGOGIANNIS N G.The inflammatory response in myocardial injury,repair,and remodelling[J].Nature Revieus.Cardiology.2014,11(5):255-265.
[56] MANN D L,MCMURRAY J J,PACKER M,et al.Targeted anticytokine therapy in patients with chronic heart failure:results of the Randomized Etanercept Worldwide Evaluation (RENEWAL)[J].Circulation.2004,109(13):1594-1602.
[57] CHUNG E S,PACKER M,LO K H,et al.Anti TNFTACHFI.Randomized,double-blind,placebo-controlled,pi-lot trial of infliximab,a chimeric monoclonal antibody to tumor necrosis factor-alpha,in patients with moderate-to-severe heart failure:results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial[J].Circulation.2003,107(25):3133-3140.
[58] BORDER W A,NOBLE N A.Transforming growth factor beta in tissue fibrosis[J].N Engl J Med.1994,331(19):1286-1292.
[59] JU H,ZHAO S,JASSAL D S,et al.Effect of AT1 receptor block-ade on cardiac collagen remodeling after myocardial infarction[J].Cardiovasc Res.1997,35(2):223-232.
[60] WEBER K T.Extracellular matrix remodeling in heart failure:a role for de novo angiotens in II generation[J].Circulation.1997,96(11):4065-4082.
[61] HAO J,WANG B,JONES S C,et al.Interaction between angiotensin II and smad proteins in fibroblasts in failing heart and in vitro[J].Am J Physiol Heart Circ Physiol.2000,279(6):H3020-3030.
[62] WAHL S M,HUNT D A,WAKEFIELD L M,et al.Transforming growth factor type beta induces monocyte chemotaxis and growth factor production[J].Proc Natl Acad Sci U S A.1987,84(16):5788-5792.
[63] CHEN H,LI D,SALDEEN T,et al.Transforming growth factor-beta (1) modulates oxidatively modified LDL-induced expression of adhesion molecules:role of LOX-1[J].Circ Res.2001,89(12):1155-1160.
[64] DANDAPAT A,HU C P,LI D,et al.Overexpression of TGFbeta1 by adeno-associated virus type-2 vector protects myocardium from ischemia-reperfusion injury[J].Gene Ther.2008,15(6):415-423.
[65] IKEUCHI M,TSUTSUI H,SHIOMI T,et al.Inhibition of TGF-beta signaling exacerbates early cardiac dysfunction but prevents late remodeling after infarction[J].Cardiovasc Res.2004,64(3):526-535.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录