自主神经系统调控心脏炎症反应的研究进展
|
摘要
心脏受自主神经系统的交感神经和副交感神经的双重支配,两者相互平衡,维持并调节心脏能量代谢、心率及血压。多种心脏病理状态均存在自主神经系统的失衡,表现为增强的交感神经活性及受抑制的副交感神经活性。越来越多的证据表明,过度激活的交感神经会引起心脏炎症反应。适度的炎症反应有助于心脏清除损伤组织并启动修复,而过度的炎症反应则可造成心脏损伤。近年来由于对α7烟碱型乙酰胆碱受体(α7 nicotinic acetylcholine receptor,α7nAChR)介导的胆碱能抗炎通路(cholinergic anti-inflammatory pathway, CAP)的认识,副交感神经在心脏中的抗炎作用也受到更多的关注。本文旨在总结交感神经和副交感神经对心脏炎症反应的作用及其机制,为临床干预心脏炎症反应提供新思路。
The autonomic nervous system consists of the sympathetic nervous system and the parasympathetic nervous system. These two systems control the heart and work in a reciprocal fashion to modulate myocardial energy metabolism, heart rate as well as blood pressure. Multiple cardiac pathological conditions are accompanied by autonomic imbalance, characterized by sympathetic overactivation and parasympathetic inhibition. Studies have shown that overactive sympathetic nervous system leads to increased cardiac inflammatory reaction. Orchestrated inflammatory response serves to clear dead cardiac tissue and activate reparative process, whereas excessive inflammation may result in pathological cardiac remodeling. Since the discovery of the α7 nicotinic acetylcholine receptor(α7 nAChR)-mediated cholinergic anti-inflammatory pathway(CAP), the protective effects of the parasympathetic nervous system in cardiac inflammation have attracted more attention recently. In this review, we summarized the role and underlying mechanisms of the sympathetic and parasympathetic nervous systems in cardiac inflammation, in order to provide new insight into cardiac inflammatory response in cardiovascular diseases.
The autonomic nervous system consists of the sympathetic nervous system and the parasympathetic nervous system. These two systems control the heart and work in a reciprocal fashion to modulate myocardial energy metabolism, heart rate as well as blood pressure. Multiple cardiac pathological conditions are accompanied by autonomic imbalance, characterized by sympathetic overactivation and parasympathetic inhibition. Studies have shown that overactive sympathetic nervous system leads to increased cardiac inflammatory reaction. Orchestrated inflammatory response serves to clear dead cardiac tissue and activate reparative process, whereas excessive inflammation may result in pathological cardiac remodeling. Since the discovery of the α7 nicotinic acetylcholine receptor(α7 nAChR)-mediated cholinergic anti-inflammatory pathway(CAP), the protective effects of the parasympathetic nervous system in cardiac inflammation have attracted more attention recently. In this review, we summarized the role and underlying mechanisms of the sympathetic and parasympathetic nervous systems in cardiac inflammation, in order to provide new insight into cardiac inflammatory response in cardiovascular diseases.
引文
1 Vaduganathan M,Greene SJ,Butler J,Sabbah HN,Shantsila E,Lip GY,Gheorghiade M.The immunological axis in heart failure:importance of the leukocyte differential.Heart Fail Rev 2013;18(6):835-845.
2 Yu L,Feng Z.The role of Toll-like receptor signaling in the progression of heart failure.Mediators Inflamm 2018;2018:9874109.
3 Gao W,Xiong Y,Li Q,Yang H.Inhibition of Toll-like receptor signaling as a promising therapy for inflammatory diseases:a journey from molecular to nano therapeutics.Front Physiol2017;8:508.
4 Frangogiannis NG.Inflammation in cardiac injury,repair and regeneration.Curr Opin Cardiol 2015;30(3):240-245.
5 Butts B,Gary RA,Dunbar SB,Butler J.The importance of NLRP3 inflammasome in heart failure.J Card Fail 2015;21(7):586-593.
6 Lugrin J,Parapanov R,Rosenblatt-Velin N,Rignault-Clerc S,Feihl F,Waeber B,Muller O,Vergely C,Zeller M,Tardivel A,Schneider P,Pacher P,Liaudet L.Cutting edge:IL-1alpha is a crucial danger signal triggering acute myocardial inflammation during myocardial infarction.J Immunol 2015;194(2):499-503.
7 Frati G,Schirone L,Chimenti I,Yee D,Biondi-Zoccai G,Volpe M,Sciarretta S.An overview of the inflammatory signalling mechanisms in the myocardium underlying the development of diabetic cardiomyopathy.Cardiovasc Res2017;113(4):378-388.
8 Rojas A,Delgado-Lopez F,Gonzalez I,Perez-Castro R,Romero J,Rojas I.The receptor for advanced glycation end-products:a complex signaling scenario for a promiscuous receptor.Cell Signal 2013;25(3):609-614.
9 Luo B,Huang F,Liu Y,Liang Y,Wei Z,Ke H,Zeng Z,Huang W,He Y.NLRP3 inflammasome as a molecular marker in diabetic cardiomyopathy.Front Physiol 2017;8:519.
10 Frangogiannis NG.Regulation of the inflammatory response in cardiac repair.Circ Res 2012;110(1):159-173.
11 Turer AT,Hill JA,Elmquist JK,Scherer PE.Adipose tissue biology and cardiomyopathy:translational implications.Circ Res 2012;111(12):1565-1577.
12 Donath MY,Dalmas E,Sauter NS,Boni-Schnetzler M.Inflammation in obesity and diabetes:islet dysfunction and therapeutic opportunity.Cell Metab 2013;17(6):860-872.
13 Ridker PM,Everett BM,Thuren T,MacFadyen JG,Chang WH,Ballantyne C,Fonseca F,Nicolau J,Koenig W,Anker SD,Kastelein J,Cornel JH,Pais P,Pella D,Genest J,Cifkova R,Lorenzatti A,Forster T,Kobalava Z,Vida-Simiti L,Flather M,Shimokawa H,Ogawa H,Dellborg M,Rossi P,Troquay R,Libby P,Glynn RJ;CANTOS Trial Group.Antiinflammatory therapy with canakinumab for atherosclerotic disease.N Engl J Med 2017;377(12):1119-1131.
14 Ripplinger CM,Noujaim SF,Linz D.The nervous heart.Prog Biophys Mol Biol 2016;120(1-3):199-209.
15 Wake E,Brack K.Characterization of the intrinsic cardiac nervous system.Auton Neurosci 2016;199:3-16.
16 Brack KE.The heart’s‘little brain’controlling cardiac function in the rabbit.Exp Physiol 2015;100(4):348-353.
17 de Lucia C,Femminella GD,Gambino G,Pagano G,Allocca E,Rengo C,Silvestri C,Leosco D,Ferrara N,Rengo G.Adrenal adrenoceptors in heart failure.Front Physiol 2014;5:246.
18 Y-Hassan S,Tornvall P.Epidemiology,pathogenesis,and management of takotsubo syndrome.Clin Auton Res 2018;28(1):53-65.
19 Pelliccia F,Kaski JC,Crea F,Camici PG.Pathophysiology of Takotsubo syndrome.Circulation 2017;135(24):2426-2441.
20 Wittstein IS,Thiemann DR,Lima JA,Baughman KL,Schulman SP,Gerstenblith G,Wu KC,Rade JJ,Bivalacqua TJ,Champion HC.Neurohumoral features of myocardial stunning due to sudden emotional stress.N Engl J Med 2005;352(6):539-548.
21 Kakinuma Y.Future perspectives of a cardiac non-neuronal acetylcholine system targeting cardiovascular diseases as an adjunctive tool for metabolic intervention.Int Immunopharmacol 2015;29(1):185-188.
22 Gavioli M,Lara A,Almeida PW,Lima AM,Damasceno DD,Rocha-Resende C,Ladeira M,Resende RR,Martinelli PM,Melo MB,Brum PC,Fontes MA,Souza SR,Prado MA,Guatimosim S.Cholinergic signaling exerts protective effects in models of sympathetic hyperactivity-induced cardiac dysfunction.PLoS One 2014;9(7):e100179.
23 Huang CJ,Webb HE,Zourdos MC,Acevedo EO.Cardiovascular reactivity,stress,and physical activity.Front Physiol2013;4:314.
24 Ziegler KA,Ahles A,Wille T,Kerler J,Ramanujam D,Engelhardt S.Local sympathetic denervation attenuates myocardial inflammation and improves cardiac function after myocardial infarction in mice.Cardiovasc Res 2018;114(2):291-299.
25 Diaz-Araya G,Vivar R,Humeres C,Boza P,Bolivar S,Munoz C.Cardiac fibroblasts as sentinel cells in cardiac tissue:Receptors,signaling pathways and cellular functions.Pharmacol Res 2015;101:30-40.
26 Marino F,Cosentino M.Adrenergic modulation of immune cells:an update.Amino Acids 2013;45(1):55-71.
27 Scanzano A,Schembri L,Rasini E,Luini A,Dallatorre J,Legnaro M,Bombelli R,Congiu T,Cosentino M,Marino F.Adrenergic modulation of migration,CD11b and CD18expression,ROS and interleukin-8 production by human polymorphonuclear leukocytes.Inflamm Res 2015;64(2):127-135.
28 Mohan ML,Vasudevan NT,Naga PS.Proinflammatory cytokines mediate GPCR dysfunction.J Cardiovasc Pharmacol2017;70(2):61-73.
29 Xiao H,Li H,Wang JJ,Zhang JS,Shen J,An XB,Zhang CC,Wu JM,Song Y,Wang XY,Yu HY,Deng XN,Li ZJ,Xu M,Lu ZZ,Du J,Gao W,Zhang AH,Feng Y,Zhang YY.IL-18 cleavage triggers cardiac inflammation and fibrosis upon beta-adrenergic insult.Eur Heart J 2018;39(1):60-69.
30 Liu L,Wang Y,Cao ZY,Wang MM,Liu XM,Gao T,Hu QK,Yuan WJ,Lin L.Up-regulated TLR4 in cardiomyocytes exacerbates heart failure after long-term myocardial infarction.J Cell Mol Med 2015;19(12):2728-2740.
31 Tian J,Guo X,Liu XM,Liu L,Weng QF,Dong SJ,Knowlton AA,Yuan WJ,Lin L.Extracellular HSP60 induces inflammation through activating and up-regulating TLRs in cardiomyocytes.Cardiovasc Res 2013;98(3):391-401.
32 Soraya H,Farajnia S,Khani S,Rameshrad M,Khorrami A,Banani A,Maleki-Dizaji N,Garjani A.Short-term treatment with metformin suppresses toll like receptors(TLRs)activity in isoproterenol-induced myocardial infarction in rat:are AMPK and TLRs connected?Int Immunopharmacol 2012;14(4):785-791.
33 Kizaki T,Shirato K,Sakurai T,Ogasawara JE,Oh-ishi S,Matsuoka T,Izawa T,Imaizumi K,Haga S,Ohno H.Beta2-adrenergic receptor regulate Toll-like receptor 4-induced late-phase NF-kappaB activation.Mol Immunol2009;46(6):1195-1203.
34 Zhang J,Xiao H,Shen J,Wang N,Zhang Y.Different roles of beta-arrestin and the PKA pathway in mitochondrial ROSproduction induced by acute beta-adrenergic receptor stimulation in neonatal mouse cardiomyocytes.Biochem Biophys Res Commun 2017;489(4):393-398.
35 Chandrasekar B,Marelli-Berg FM,Tone M,Bysani S,Prabhu SD,Murray DR.Beta-adrenergic stimulation induces interleukin-18 expression via beta2-AR,PI3K,Akt,IKK,and NF-kappaB.Biochem Biophys Res Commun 2004;319(2):304-311.
36 Murray DR,Mummidi S,Valente AJ,Yoshida T,Somanna NK,Delafontaine P,Dinarello CA,Chandrasekar B.beta2adrenergic activation induces the expression of IL-18 binding protein,a potent inhibitor of isoproterenol induced cardiomyocyte hypertrophy in vitro and myocardial hypertrophy in vivo.J Mol Cell Cardiol 2012;52(1):206-218.
37 Melendez GC,McLarty JL,Levick SP,Du Y,Janicki JS,Brower GL.Interleukin 6 mediates myocardial fibrosis,concentric hypertrophy,and diastolic dysfunction in rats.Hypertension 2010;56(2):225-231.
38 Vasan RS,Sullivan LM,Roubenoff R,Dinarello CA,Harris T,Benjamin EJ,Sawyer DB,Levy D,Wilson PW,D’Agostino RB.Inflammatory markers and risk of heart failure in elderly subjects without prior myocardial infarction:the Framingham Heart Study.Circulation 2003;107(11):1486-1491.
39 Yin F,Li P,Zheng M,Chen L,Xu Q,Chen K,Wang YY,Zhang YY,Han C.Interleukin-6 family of cytokines mediates isoproterenol-induced delayed STAT3 activation in mouse heart.J Biol Chem 2003;278(23):21070-21075.
40 Chen C,Du J,Feng W,Song Y,Lu Z,Xu M,Li Z,Zhang Y.beta-Adrenergic receptors stimulate interleukin-6 production through Epac-dependent activation of PKCdelta/p38 MAPKsignalling in neonatal mouse cardiac fibroblasts.Br J Pharmacol 2012;166(2):676-688.
41 Lorton D,Bellinger DL.Molecular mechanisms underlying beta-adrenergic receptor-mediated cross-talk between sympathetic neurons and immune cells.Int J Mol Sci 2015;16(3):5635-5665.
42 Grisanti LA,Gumpert AM,Traynham CJ,Gorsky JE,Repas AA,Gao E,Carter RL,Yu D,Calvert JW,Garcia AP,Ibanez B,Rabinowitz JE,Koch WJ,Tilley DG.Leukocyte-expressed beta2-adrenergic receptors are essential for survival after acute myocardial injury.Circulation 2016;134(2):153-167.
43 Grisanti LA,Traynham CJ,Repas AA,Gao E,Koch WJ,Tilley DG.beta2-Adrenergic receptor-dependent chemokine receptor 2 expression regulates leukocyte recruitment to the heart following acute injury.Proc Natl Acad Sci U S A 2016;113(52):15126-15131.
44 Ismahil MA,Hamid T,Bansal SS,Patel B,Kingery JR,Prabhu SD.Remodeling of the mononuclear phagocyte network underlies chronic inflammation and disease progression in heart failure:critical importance of the cardiosplenic axis.Circ Res 2014;114(2):266-282.
45 Cheng X,Liao YH,Ge H,Li B,Zhang J,Yuan J,Wang M,Liu Y,Guo Z,Chen J,Zhang J,Zhang L.TH1/TH2 functional imbalance after acute myocardial infarction:coronary arterial inflammation or myocardial inflammation.J Clin Immunol2005;25(3):246-253.
46 Tian X,Zhang L,Hou Y,Xu W,Dong Y,Liu J,Liang J.Effects of cAMP and beta-adrenergic receptor antagonists on the function of peripheral T helper lymphocytes in patients with heart failure.Neuroimmunomodulation 2011;18(2):73-78.
47 Grisanti LA,Woster AP,Dahlman J,Sauter ER,Combs CK,Porter JE.alpha1-adrenergic receptors positively regulate Toll-like receptor cytokine production from human monocytes and macrophages.J Pharmacol Exp Ther 2011;338(2):648-657.
48 Horstmann JP,Marzi I,Relja B.Adrenergic stimulation alters the expression of inflammasome components and interleukins in primary human monocytes.Exp Ther Med 2016;11(1):297-302.
49 Perez DM,Papay RS,Shi T.alpha1-Adrenergic receptor stimulates interleukin-6 expression and secretion through both mRNA stability and transcriptional regulation:involvement of p38 mitogen-activated protein kinase and nuclear factor-kappaB.Mol Pharmacol 2009;76(1):144-152.
50 Papay RS,Shi T,Piascik MT,Naga PS,Perez DM.alpha(1)A-adrenergic receptors regulate cardiac hypertrophy in vivo through interleukin-6 secretion.Mol Pharmacol 2013;83(5):939-948.
51 Shames BD,Barton HH,Reznikov LL,Cairns CB,Banerjee A,Harken AH,Meng X.Ischemia alone is sufficient to induce TNF-alpha mRNA and peptide in the myocardium.Shock2002;17(2):114-119.
52 Kong SS,Liu JJ,Hwang TC,Yu XJ,Lu Y,Zang WJ.Tumour necrosis factor-alpha and its receptors in the beneficial effects of vagal stimulation after myocardial infarction in rats.Clin Exp Pharmacol Physiol 2011;38(5):300-306.
53 Li-Sha G,Xing-Xing C,Lian-Pin W,De-Pu Z,Xiao-Wei L,Jia-Feng L,Yue-Chun L.Right cervical vagotomy aggravates viral myocarditis in mice via the cholinergic anti-inflammatory pathway.Front Pharmacol 2017;8:25.
54 Roy A,Guatimosim S,Prado VF,Gros R,Prado MA.Cholinergic activity as a new target in diseases of the heart.Mol Med 2015;20:527-537.
55 Hoover DB.Cholinergic modulation of the immune system presents new approaches for treating inflammation.Pharmacol Ther 2017;179:1-16.
56 Tsoyi K,Jang HJ,Kim JW,Chang HK,Lee YS,Pae HO,Kim HJ,Seo HG,Lee JH,Chung HT,Chang KC.Stimulation of alpha7 nicotinic acetylcholine receptor by nicotine attenuates inflammatory response in macrophages and improves survival in experimental model of sepsis through heme oxygenase-1 induction.Antioxid Redox Signal 2011;14(11):2057-2070.
57 Leib C,Goser S,Luthje D,Ottl R,Tretter T,Lasitschka F,Zittrich S,Pfitzer G,Katus HA,Kaya Z.Role of the cholinergic antiinflammatory pathway in murine autoimmune myocarditis.Circ Res 2011;109(2):130-140.
58 Xiong J,Yuan YJ,Xue FS,Wang Q,Cheng Y,Li RP,Liao X,Liu JH.Postconditioning with alpha7nAChR agonist attenuates systemic inflammatory response to myocardial ischemia--reperfusion injury in rats.Inflammation 2012;35(4):1357-1364.
59 Zhang J,Yong Y,Li X,Hu Y,Wang J,Wang YQ,Song W,Chen WT,Xie J,Chen XM,Lv X,Hou LL,Wang K,Zhou J,Wang XR,Song JG.Vagal modulation of high mobility group box-1 protein mediates electroacupuncture-induced cardioprotection in ischemia-reperfusion injury.Sci Rep2015;5:15503.
60 Zhao M,He X,Bi XY,Yu XJ,Gil WW,Zang WJ.Vagal stimulation triggers peripheral vascular protection through the cholinergic anti-inflammatory pathway in a rat model of myocardial ischemia/reperfusion.Basic Res Cardiol 2013;108(3):345.
61 Kucera M,Hrabovska A.Cholinergic system of the heart.Ceska Slov Farm 2015;64(6):254-263.
62 Kawashima K,Fujii T,Moriwaki Y,Misawa H,Horiguchi K.Non-neuronal cholinergic system in regulation of immune function with a focus on alpha7 nAChRs.Int Immunopharmacol 2015;29(1):127-134.
63 Li DL,Liu JJ,Liu BH,Hu H,Sun L,Miao Y,Xu HF,Yu XJ,Ma X,Ren J,Zang WJ.Acetylcholine inhibits hypoxia-induced tumor necrosis factor-alpha production via regulation of MAPKs phosphorylation in cardiomyocytes.J Cell Physiol2011;226(4):1052-1059.
64 de La Fuente RN,Rodrigues B,Moraes-Silva IC,Souza LE,Sirvente R,Mostarda C,De Angelis K,Soares PP,Lacchini S,Consolim-Colombo F,Irigoyen MC.Cholinergic stimulation with pyridostigmine improves autonomic function in infarcted rats.Clin Exp Pharmacol Physiol 2013;40(9):610-616.
65 Rocha JA,Ribeiro SP,Franca CM,Coelho O,Alves G,Lacchini S,Kallas EG,Irigoyen MC,Consolim-Colombo FM.Increase in cholinergic modulation with pyridostigmine induces anti-inflammatory cell recruitment soon after acute myocardial infarction in rats.Am J Physiol Regul Integr Comp Physiol 2016;310(8):R697-R706.
66 Bezerra OC,Franca CM,Rocha JA,Neves GA,Souza P,Teixeira GM,Malfitano C,Loleiro T,Dourado PM,Llesuy S,de Angelis K,Irigoyen M,Ulloa L,Consolim-Colombo FM.Cholinergic stimulation improves oxidative stress and inflammation in experimental myocardial Infarction.Sci Rep 2017;7(1):13687.
67 He X,Zhao M,Bi X,Sun L,Yu X,Zhao M,Zang W.Novel strategies and underlying protective mechanisms of modulation of vagal activity in cardiovascular diseases.Br J Pharmacol 2015;172(23):5489-5500.
2 Yu L,Feng Z.The role of Toll-like receptor signaling in the progression of heart failure.Mediators Inflamm 2018;2018:9874109.
3 Gao W,Xiong Y,Li Q,Yang H.Inhibition of Toll-like receptor signaling as a promising therapy for inflammatory diseases:a journey from molecular to nano therapeutics.Front Physiol2017;8:508.
4 Frangogiannis NG.Inflammation in cardiac injury,repair and regeneration.Curr Opin Cardiol 2015;30(3):240-245.
5 Butts B,Gary RA,Dunbar SB,Butler J.The importance of NLRP3 inflammasome in heart failure.J Card Fail 2015;21(7):586-593.
6 Lugrin J,Parapanov R,Rosenblatt-Velin N,Rignault-Clerc S,Feihl F,Waeber B,Muller O,Vergely C,Zeller M,Tardivel A,Schneider P,Pacher P,Liaudet L.Cutting edge:IL-1alpha is a crucial danger signal triggering acute myocardial inflammation during myocardial infarction.J Immunol 2015;194(2):499-503.
7 Frati G,Schirone L,Chimenti I,Yee D,Biondi-Zoccai G,Volpe M,Sciarretta S.An overview of the inflammatory signalling mechanisms in the myocardium underlying the development of diabetic cardiomyopathy.Cardiovasc Res2017;113(4):378-388.
8 Rojas A,Delgado-Lopez F,Gonzalez I,Perez-Castro R,Romero J,Rojas I.The receptor for advanced glycation end-products:a complex signaling scenario for a promiscuous receptor.Cell Signal 2013;25(3):609-614.
9 Luo B,Huang F,Liu Y,Liang Y,Wei Z,Ke H,Zeng Z,Huang W,He Y.NLRP3 inflammasome as a molecular marker in diabetic cardiomyopathy.Front Physiol 2017;8:519.
10 Frangogiannis NG.Regulation of the inflammatory response in cardiac repair.Circ Res 2012;110(1):159-173.
11 Turer AT,Hill JA,Elmquist JK,Scherer PE.Adipose tissue biology and cardiomyopathy:translational implications.Circ Res 2012;111(12):1565-1577.
12 Donath MY,Dalmas E,Sauter NS,Boni-Schnetzler M.Inflammation in obesity and diabetes:islet dysfunction and therapeutic opportunity.Cell Metab 2013;17(6):860-872.
13 Ridker PM,Everett BM,Thuren T,MacFadyen JG,Chang WH,Ballantyne C,Fonseca F,Nicolau J,Koenig W,Anker SD,Kastelein J,Cornel JH,Pais P,Pella D,Genest J,Cifkova R,Lorenzatti A,Forster T,Kobalava Z,Vida-Simiti L,Flather M,Shimokawa H,Ogawa H,Dellborg M,Rossi P,Troquay R,Libby P,Glynn RJ;CANTOS Trial Group.Antiinflammatory therapy with canakinumab for atherosclerotic disease.N Engl J Med 2017;377(12):1119-1131.
14 Ripplinger CM,Noujaim SF,Linz D.The nervous heart.Prog Biophys Mol Biol 2016;120(1-3):199-209.
15 Wake E,Brack K.Characterization of the intrinsic cardiac nervous system.Auton Neurosci 2016;199:3-16.
16 Brack KE.The heart’s‘little brain’controlling cardiac function in the rabbit.Exp Physiol 2015;100(4):348-353.
17 de Lucia C,Femminella GD,Gambino G,Pagano G,Allocca E,Rengo C,Silvestri C,Leosco D,Ferrara N,Rengo G.Adrenal adrenoceptors in heart failure.Front Physiol 2014;5:246.
18 Y-Hassan S,Tornvall P.Epidemiology,pathogenesis,and management of takotsubo syndrome.Clin Auton Res 2018;28(1):53-65.
19 Pelliccia F,Kaski JC,Crea F,Camici PG.Pathophysiology of Takotsubo syndrome.Circulation 2017;135(24):2426-2441.
20 Wittstein IS,Thiemann DR,Lima JA,Baughman KL,Schulman SP,Gerstenblith G,Wu KC,Rade JJ,Bivalacqua TJ,Champion HC.Neurohumoral features of myocardial stunning due to sudden emotional stress.N Engl J Med 2005;352(6):539-548.
21 Kakinuma Y.Future perspectives of a cardiac non-neuronal acetylcholine system targeting cardiovascular diseases as an adjunctive tool for metabolic intervention.Int Immunopharmacol 2015;29(1):185-188.
22 Gavioli M,Lara A,Almeida PW,Lima AM,Damasceno DD,Rocha-Resende C,Ladeira M,Resende RR,Martinelli PM,Melo MB,Brum PC,Fontes MA,Souza SR,Prado MA,Guatimosim S.Cholinergic signaling exerts protective effects in models of sympathetic hyperactivity-induced cardiac dysfunction.PLoS One 2014;9(7):e100179.
23 Huang CJ,Webb HE,Zourdos MC,Acevedo EO.Cardiovascular reactivity,stress,and physical activity.Front Physiol2013;4:314.
24 Ziegler KA,Ahles A,Wille T,Kerler J,Ramanujam D,Engelhardt S.Local sympathetic denervation attenuates myocardial inflammation and improves cardiac function after myocardial infarction in mice.Cardiovasc Res 2018;114(2):291-299.
25 Diaz-Araya G,Vivar R,Humeres C,Boza P,Bolivar S,Munoz C.Cardiac fibroblasts as sentinel cells in cardiac tissue:Receptors,signaling pathways and cellular functions.Pharmacol Res 2015;101:30-40.
26 Marino F,Cosentino M.Adrenergic modulation of immune cells:an update.Amino Acids 2013;45(1):55-71.
27 Scanzano A,Schembri L,Rasini E,Luini A,Dallatorre J,Legnaro M,Bombelli R,Congiu T,Cosentino M,Marino F.Adrenergic modulation of migration,CD11b and CD18expression,ROS and interleukin-8 production by human polymorphonuclear leukocytes.Inflamm Res 2015;64(2):127-135.
28 Mohan ML,Vasudevan NT,Naga PS.Proinflammatory cytokines mediate GPCR dysfunction.J Cardiovasc Pharmacol2017;70(2):61-73.
29 Xiao H,Li H,Wang JJ,Zhang JS,Shen J,An XB,Zhang CC,Wu JM,Song Y,Wang XY,Yu HY,Deng XN,Li ZJ,Xu M,Lu ZZ,Du J,Gao W,Zhang AH,Feng Y,Zhang YY.IL-18 cleavage triggers cardiac inflammation and fibrosis upon beta-adrenergic insult.Eur Heart J 2018;39(1):60-69.
30 Liu L,Wang Y,Cao ZY,Wang MM,Liu XM,Gao T,Hu QK,Yuan WJ,Lin L.Up-regulated TLR4 in cardiomyocytes exacerbates heart failure after long-term myocardial infarction.J Cell Mol Med 2015;19(12):2728-2740.
31 Tian J,Guo X,Liu XM,Liu L,Weng QF,Dong SJ,Knowlton AA,Yuan WJ,Lin L.Extracellular HSP60 induces inflammation through activating and up-regulating TLRs in cardiomyocytes.Cardiovasc Res 2013;98(3):391-401.
32 Soraya H,Farajnia S,Khani S,Rameshrad M,Khorrami A,Banani A,Maleki-Dizaji N,Garjani A.Short-term treatment with metformin suppresses toll like receptors(TLRs)activity in isoproterenol-induced myocardial infarction in rat:are AMPK and TLRs connected?Int Immunopharmacol 2012;14(4):785-791.
33 Kizaki T,Shirato K,Sakurai T,Ogasawara JE,Oh-ishi S,Matsuoka T,Izawa T,Imaizumi K,Haga S,Ohno H.Beta2-adrenergic receptor regulate Toll-like receptor 4-induced late-phase NF-kappaB activation.Mol Immunol2009;46(6):1195-1203.
34 Zhang J,Xiao H,Shen J,Wang N,Zhang Y.Different roles of beta-arrestin and the PKA pathway in mitochondrial ROSproduction induced by acute beta-adrenergic receptor stimulation in neonatal mouse cardiomyocytes.Biochem Biophys Res Commun 2017;489(4):393-398.
35 Chandrasekar B,Marelli-Berg FM,Tone M,Bysani S,Prabhu SD,Murray DR.Beta-adrenergic stimulation induces interleukin-18 expression via beta2-AR,PI3K,Akt,IKK,and NF-kappaB.Biochem Biophys Res Commun 2004;319(2):304-311.
36 Murray DR,Mummidi S,Valente AJ,Yoshida T,Somanna NK,Delafontaine P,Dinarello CA,Chandrasekar B.beta2adrenergic activation induces the expression of IL-18 binding protein,a potent inhibitor of isoproterenol induced cardiomyocyte hypertrophy in vitro and myocardial hypertrophy in vivo.J Mol Cell Cardiol 2012;52(1):206-218.
37 Melendez GC,McLarty JL,Levick SP,Du Y,Janicki JS,Brower GL.Interleukin 6 mediates myocardial fibrosis,concentric hypertrophy,and diastolic dysfunction in rats.Hypertension 2010;56(2):225-231.
38 Vasan RS,Sullivan LM,Roubenoff R,Dinarello CA,Harris T,Benjamin EJ,Sawyer DB,Levy D,Wilson PW,D’Agostino RB.Inflammatory markers and risk of heart failure in elderly subjects without prior myocardial infarction:the Framingham Heart Study.Circulation 2003;107(11):1486-1491.
39 Yin F,Li P,Zheng M,Chen L,Xu Q,Chen K,Wang YY,Zhang YY,Han C.Interleukin-6 family of cytokines mediates isoproterenol-induced delayed STAT3 activation in mouse heart.J Biol Chem 2003;278(23):21070-21075.
40 Chen C,Du J,Feng W,Song Y,Lu Z,Xu M,Li Z,Zhang Y.beta-Adrenergic receptors stimulate interleukin-6 production through Epac-dependent activation of PKCdelta/p38 MAPKsignalling in neonatal mouse cardiac fibroblasts.Br J Pharmacol 2012;166(2):676-688.
41 Lorton D,Bellinger DL.Molecular mechanisms underlying beta-adrenergic receptor-mediated cross-talk between sympathetic neurons and immune cells.Int J Mol Sci 2015;16(3):5635-5665.
42 Grisanti LA,Gumpert AM,Traynham CJ,Gorsky JE,Repas AA,Gao E,Carter RL,Yu D,Calvert JW,Garcia AP,Ibanez B,Rabinowitz JE,Koch WJ,Tilley DG.Leukocyte-expressed beta2-adrenergic receptors are essential for survival after acute myocardial injury.Circulation 2016;134(2):153-167.
43 Grisanti LA,Traynham CJ,Repas AA,Gao E,Koch WJ,Tilley DG.beta2-Adrenergic receptor-dependent chemokine receptor 2 expression regulates leukocyte recruitment to the heart following acute injury.Proc Natl Acad Sci U S A 2016;113(52):15126-15131.
44 Ismahil MA,Hamid T,Bansal SS,Patel B,Kingery JR,Prabhu SD.Remodeling of the mononuclear phagocyte network underlies chronic inflammation and disease progression in heart failure:critical importance of the cardiosplenic axis.Circ Res 2014;114(2):266-282.
45 Cheng X,Liao YH,Ge H,Li B,Zhang J,Yuan J,Wang M,Liu Y,Guo Z,Chen J,Zhang J,Zhang L.TH1/TH2 functional imbalance after acute myocardial infarction:coronary arterial inflammation or myocardial inflammation.J Clin Immunol2005;25(3):246-253.
46 Tian X,Zhang L,Hou Y,Xu W,Dong Y,Liu J,Liang J.Effects of cAMP and beta-adrenergic receptor antagonists on the function of peripheral T helper lymphocytes in patients with heart failure.Neuroimmunomodulation 2011;18(2):73-78.
47 Grisanti LA,Woster AP,Dahlman J,Sauter ER,Combs CK,Porter JE.alpha1-adrenergic receptors positively regulate Toll-like receptor cytokine production from human monocytes and macrophages.J Pharmacol Exp Ther 2011;338(2):648-657.
48 Horstmann JP,Marzi I,Relja B.Adrenergic stimulation alters the expression of inflammasome components and interleukins in primary human monocytes.Exp Ther Med 2016;11(1):297-302.
49 Perez DM,Papay RS,Shi T.alpha1-Adrenergic receptor stimulates interleukin-6 expression and secretion through both mRNA stability and transcriptional regulation:involvement of p38 mitogen-activated protein kinase and nuclear factor-kappaB.Mol Pharmacol 2009;76(1):144-152.
50 Papay RS,Shi T,Piascik MT,Naga PS,Perez DM.alpha(1)A-adrenergic receptors regulate cardiac hypertrophy in vivo through interleukin-6 secretion.Mol Pharmacol 2013;83(5):939-948.
51 Shames BD,Barton HH,Reznikov LL,Cairns CB,Banerjee A,Harken AH,Meng X.Ischemia alone is sufficient to induce TNF-alpha mRNA and peptide in the myocardium.Shock2002;17(2):114-119.
52 Kong SS,Liu JJ,Hwang TC,Yu XJ,Lu Y,Zang WJ.Tumour necrosis factor-alpha and its receptors in the beneficial effects of vagal stimulation after myocardial infarction in rats.Clin Exp Pharmacol Physiol 2011;38(5):300-306.
53 Li-Sha G,Xing-Xing C,Lian-Pin W,De-Pu Z,Xiao-Wei L,Jia-Feng L,Yue-Chun L.Right cervical vagotomy aggravates viral myocarditis in mice via the cholinergic anti-inflammatory pathway.Front Pharmacol 2017;8:25.
54 Roy A,Guatimosim S,Prado VF,Gros R,Prado MA.Cholinergic activity as a new target in diseases of the heart.Mol Med 2015;20:527-537.
55 Hoover DB.Cholinergic modulation of the immune system presents new approaches for treating inflammation.Pharmacol Ther 2017;179:1-16.
56 Tsoyi K,Jang HJ,Kim JW,Chang HK,Lee YS,Pae HO,Kim HJ,Seo HG,Lee JH,Chung HT,Chang KC.Stimulation of alpha7 nicotinic acetylcholine receptor by nicotine attenuates inflammatory response in macrophages and improves survival in experimental model of sepsis through heme oxygenase-1 induction.Antioxid Redox Signal 2011;14(11):2057-2070.
57 Leib C,Goser S,Luthje D,Ottl R,Tretter T,Lasitschka F,Zittrich S,Pfitzer G,Katus HA,Kaya Z.Role of the cholinergic antiinflammatory pathway in murine autoimmune myocarditis.Circ Res 2011;109(2):130-140.
58 Xiong J,Yuan YJ,Xue FS,Wang Q,Cheng Y,Li RP,Liao X,Liu JH.Postconditioning with alpha7nAChR agonist attenuates systemic inflammatory response to myocardial ischemia--reperfusion injury in rats.Inflammation 2012;35(4):1357-1364.
59 Zhang J,Yong Y,Li X,Hu Y,Wang J,Wang YQ,Song W,Chen WT,Xie J,Chen XM,Lv X,Hou LL,Wang K,Zhou J,Wang XR,Song JG.Vagal modulation of high mobility group box-1 protein mediates electroacupuncture-induced cardioprotection in ischemia-reperfusion injury.Sci Rep2015;5:15503.
60 Zhao M,He X,Bi XY,Yu XJ,Gil WW,Zang WJ.Vagal stimulation triggers peripheral vascular protection through the cholinergic anti-inflammatory pathway in a rat model of myocardial ischemia/reperfusion.Basic Res Cardiol 2013;108(3):345.
61 Kucera M,Hrabovska A.Cholinergic system of the heart.Ceska Slov Farm 2015;64(6):254-263.
62 Kawashima K,Fujii T,Moriwaki Y,Misawa H,Horiguchi K.Non-neuronal cholinergic system in regulation of immune function with a focus on alpha7 nAChRs.Int Immunopharmacol 2015;29(1):127-134.
63 Li DL,Liu JJ,Liu BH,Hu H,Sun L,Miao Y,Xu HF,Yu XJ,Ma X,Ren J,Zang WJ.Acetylcholine inhibits hypoxia-induced tumor necrosis factor-alpha production via regulation of MAPKs phosphorylation in cardiomyocytes.J Cell Physiol2011;226(4):1052-1059.
64 de La Fuente RN,Rodrigues B,Moraes-Silva IC,Souza LE,Sirvente R,Mostarda C,De Angelis K,Soares PP,Lacchini S,Consolim-Colombo F,Irigoyen MC.Cholinergic stimulation with pyridostigmine improves autonomic function in infarcted rats.Clin Exp Pharmacol Physiol 2013;40(9):610-616.
65 Rocha JA,Ribeiro SP,Franca CM,Coelho O,Alves G,Lacchini S,Kallas EG,Irigoyen MC,Consolim-Colombo FM.Increase in cholinergic modulation with pyridostigmine induces anti-inflammatory cell recruitment soon after acute myocardial infarction in rats.Am J Physiol Regul Integr Comp Physiol 2016;310(8):R697-R706.
66 Bezerra OC,Franca CM,Rocha JA,Neves GA,Souza P,Teixeira GM,Malfitano C,Loleiro T,Dourado PM,Llesuy S,de Angelis K,Irigoyen M,Ulloa L,Consolim-Colombo FM.Cholinergic stimulation improves oxidative stress and inflammation in experimental myocardial Infarction.Sci Rep 2017;7(1):13687.
67 He X,Zhao M,Bi X,Sun L,Yu X,Zhao M,Zang W.Novel strategies and underlying protective mechanisms of modulation of vagal activity in cardiovascular diseases.Br J Pharmacol 2015;172(23):5489-5500.