炎症Caspase调控固有免疫在心血管疾病中的作用
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摘要
越来越多的证据表明,慢性炎症与高血压、动脉粥样硬化等心血管疾病密切相关。半胱天冬氨酸蛋白水解酶(Caspase)亚型Caspase-1、4、5和11被称为炎症Caspase,通过促进炎症因子的成熟与释放,诱导放大炎症反应,激活固有免疫应答。炎症Caspase作用机制包括两方面,一方面激活模式识别受体NLRP3炎症小体,促进炎症因子白细胞介素1β(IL-1β)和IL-18的剪切成熟,另一方面剪切Gasdermin D形成具有膜上打孔作用的N端,导致细胞焦亡,促进炎症因子释放。文章就炎症Caspase在心血管疾病中的作用进行综述。
More and more studies have revealed that inflammation plays an important role in cardiovascular diseases, including hypertension and atherosclerosis et al. Caspase-1, caspase-4, caspase-5 and caspase-11 are named as inflammatory caspase, which cause the mature and secretion of inflammatory cytokines. Inflammatory caspase can induce and magnify inflammatory response that represents a new paradigm in innate immunity. In addition to mediating cleavage of the NLRP3 inflammasome-associated cytokines interleukin 1 beta(IL-1β) and IL-18, inflammatory caspase modulate distinct forms of pyroptosis by shearing gasdermin D into N-terminal fragment that showed pore-forming activity, while pyroptosis of cells release a large number of inflammatory cytokines. This study will discuss the role of inflammatory caspase in cardiovascular diseases.
More and more studies have revealed that inflammation plays an important role in cardiovascular diseases, including hypertension and atherosclerosis et al. Caspase-1, caspase-4, caspase-5 and caspase-11 are named as inflammatory caspase, which cause the mature and secretion of inflammatory cytokines. Inflammatory caspase can induce and magnify inflammatory response that represents a new paradigm in innate immunity. In addition to mediating cleavage of the NLRP3 inflammasome-associated cytokines interleukin 1 beta(IL-1β) and IL-18, inflammatory caspase modulate distinct forms of pyroptosis by shearing gasdermin D into N-terminal fragment that showed pore-forming activity, while pyroptosis of cells release a large number of inflammatory cytokines. This study will discuss the role of inflammatory caspase in cardiovascular diseases.
引文
[1] Edsfeldt A,Grufman H,Asciutto G,et al.Circulating cytokines reflect the expression of pro-inflammatory cytokines in atherosclerotic plaques[J].Atherosclerosis,2015,241(2):443-449.
[2] Iskandar R,Liu S,Xiang F,et al.Expression of pericardial fluid T-cells and related inflammatory cytokines in patients with chronic heart failure [J].Exp Ther Med,2017,5(13):1850-1858.
[3] Ridker PM,Cushman M,Stampfer MJ,et al.Inflammation,aspirin,and the risk of cardiovascular disease in apparently healthy men[J].N Engl J Med,1997,336(14):973-979.
[4] Ridker PM,Hennekens CH,Buring JE,et al.C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women[J].N Engl J Med,2000,342(12):836-843.
[5] Everett BM,Pradhan AD,Solomon DH,et al.Rationale and design of the cardiovascular inflammation reduction trial:a test of the inflammatory hypothesis of atherothrombosis[J].Am Heart J,2013,166(2):199-207.
[6] Ridker PM,Thuren T,Zalewski A,et al.Interleukin-1beta inhibition and the prevention of recurrent cardiovascular events:rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS)[J].Am Heart J,2011,162(4):597-605.
[7] Hudson BI,Lippman ME.Targeting RAGE signaling in inflammatory disease[J].Annu Rev Med,2018,69:349-364.
[8] Chen X,Cui R,Li R,et al.Development of pristane induced mice model for lupus with atherosclerosis and analysis of TLR expression[J].Clin Exp Rheumatol,2016,34(4):600-608.
[9] Zhou W,Chen C,Chen Z,et al.NLRP3:a novel mediator in cardiovascular disease[J].J Immunol Res,2018,2018:5702103.
[10] Shalini S,Dorstyn L,Dawar S,et al.Old,new and emerging functions of caspases[J].Cell Death Differ,2015,22(4):526-539.
[11] Saleh M,Vaillancourt JP,Graham RK,et al.Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms[J].Nature,2004,6987(429):75-79.
[12] Man SM,Karki R,Kanneganti T.Molecular mechanisms and functions of pyroptosis,inflammatory caspases and inflammasomes in infectious diseases[J].Immunological Reviews,2017,277(1):61-75.
[13] He WT,Wan H,Hu L,et al.Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion[J].Cell Res,2015,12(25):1285-1298.
[14] Merkle S,Frantz S,Schon MP,et al.A role for caspase-1 in heart failure[J].Circ Res,2007,100(5):645-653.
[15] Burgeiro A,Fonseca AC,Espinoza D,et al.Proteostasis in epicardial versus subcutaneous adipose tissue in heart failure subjects with and without diabetes[J].Biochim Biophys Acta Mol Basis Dis,2018,1864(6PtA):2183-2198.
[16] Mann DL.Innate immunity and the failing heart:the cytokine hypothesis revisited[J].Circ Res,2015,116(7):1254-1268.
[17] Van Tassell BW,Arena R,Biondi-Zoccai G,et al.Effects of interleukin-1 blockade with anakinra on aerobic exercise capacity in patients with heart failure and preserved ejection fraction (from the D-HART Pilot Study)[J].Am J Cardiol,2013,113(2):321-327.
[18] Van Tassell BW,Abouzaki NA,Oddi Erdle C,et al.Interleukin-1 blockade in acute decompensated heart failure:a randomized,double-blinded,placebo-controlled pilot study[J].J Cardiovasc Pharmacol,2016,67(6):544-551.
[19] Toldo S,Abbate A.The NLRP3 inflammasome in acute myocardial infarction[J].Nat Rev Cardiol,2018,15(4):203-214.
[20] Aries A,Whitcomb J,Shao W,et al.Caspase-1 cleavage of transcription factor GATA4 and regulation of cardiac cell fate[J].Cell Death Dis,2014,5(12):e1566.
[21] Lee S,Choi E,Cha M,et al.Looking for pyroptosis-modulating miRNAs as a therapeutic target for improving myocardium survival[J].Mediators Inflamm,2015,2015:1-8.
[22] Yang F,Qin Y,Wang Y,et al.LncRNA KCNQ1OT1 mediates pyroptosis in diabetic cardiomyopathy[J].Cell Physiol Biochem,2018,50(4):1230-1244.
[23] Dwaich KH,Al-Amran FG,Al-Sheibani BI,et al.Melatonin effects on myocardial ischemia-reperfusion injury:impact on the outcome in patients undergoing coronary artery bypass grafting surgery[J].Int J Cardiol,2016,221:977-986.
[24] Kawaguchi M,Takahashi M,Hata T,et al.Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia/reperfusion injury[J].Circulation,2011,123(6):594-604.
[25] Wang M,Tsai BM,Kher A,et al.Role of endogenous testosterone in myocardial proinflammatory and proapoptotic signaling after acute ischemia-reperfusion[J].Am J Physiol Heart Circ Physiol,2005,288(1):H221-H226.
[26] Audia JP,Yang XM,Crockett ES,et al.Caspase-1 inhibition by VX-765 administered at reperfusion in P2Y12 receptor antagonist-treated rats provides long-term reduction in myocardial infarct size and preservation of ventricular function[J].Basic Res Cardiol,2018,113(5):32.
[27] Frantz S,Ducharme A,Sawyer D,et al.Targeted deletion of caspase-1 reduces early mortality and left ventricular dilatation following myocardial infarction[J].J Mol Cell Cardiol,2003,35(6):685-694.
[28] 廖端芳,龚勇珍,孙少卫.细胞炎症反应与脂质代谢的相互作用及调节[J].中国动脉硬化杂志,2017,25(6):623-629.
[29] Zheng F,Gong Z,Xing S,et al.Overexpression of caspase-1 in aorta of patients with coronary atherosclerosis[J].Heart Lung Circ,2014,23(11):1070-1074.
[30] Usui F,Shirasuna K,Kimura H,et al.Critical role of caspase-1 in vascular inflammation and development of atherosclerosis in Western diet-fed apolipoprotein E-deficient mice[J].Biochem Biophysical Res Commun,2012,425(2):162-168.
[31] Gage J,Hasu M,Thabet M,et al.Caspase-1 deficiency decreases atherosclerosis in apolipoprotein e-null mice[J].Canad J Cardiol,2012,28(2):222-229.
[32] Hendrikx T,Jeurissen ML,van Gorp PJ,et al.Bone marrow-specific caspase-1/11 deficiency inhibits atherosclerosis development in LDLR(-/-) mice[J].FEBS J,2015,282(12):2327-2338.
[33] Chang W,Lin J,Dong J,et al.Pyroptosis:an inflammatory cell death implicates in atherosclerosis[J].Med Hypoth,2013,81(3):484-486.
[34] Xu YJ,Zheng L,Hu YW,et al.Pyroptosis and its relationship to atherosclerosis[J].Clin Chim Acta,2018,476:28-37.
[35] Doi T,Doi S,Nakashima A,et al.Mizoribine ameliorates renal injury and hypertension along with the attenuation of renal caspase-1 expression in aldosterone-salt-treated rats[J].PLoS One,2014,9(4):e93513.
[36] Qi J,Yu X,Shi X,et al.NF-κB blockade in hypothalamic paraventricular nucleus inhibits high-salt-induced hypertension through NLRP3 and caspase-1[J].Cardiovasc Toxicol,2016,16(4):345-354.
[37] Krishnan SM,Sobey CG,Latz E,et al.IL-1beta and IL-18:inflammatory markers or mediators of hypertension?[J].Br J Pharmacol,2014,171(24):5589-5602.
[38] Martelli A,Testai L,Anzini M,et al.The novel anti-inflammatory agent VA694,endowed with both NO-releasing and COX2-selective inhibiting properties,exhibits NO-mediated positive effects on blood pressure,coronary flow and endothelium in an experimental model of hypertension and endothelial dysfunction[J].Pharmacol Res,2013,78:1-9.
[39] Pasqua T,Pagliaro P,Rocca C,et al.Role of NLRP-3 inflammasome in hypertension:a potential therapeutic target[J].Curr Pharm Biotechnol,2018,19(9):708-714 .
[40] 阿希,李玉琳,王绿娅,等.炎症小体Nlrp3在高血压小鼠心肌纤维化中的作用[J].心肺血管病杂志,2015,34(6):496-500.
[41] Yin J,You S,Liu H,et al.Role of P2X7R in the development and progression of pulmonary hypertension[J].Respir Res,2017,18(1):127.
[42] Takahashi M.NLRP3 Inflammasome as a novel player in myocardial infarction[J].Int Heart J,2014,55(2):101-105.
[43] Li X,Du N,Zhang Q,et al.MicroRNA-30d regulates cardiomyocyte pyroptosis by directly targeting foxo3a in diabetic cardiomyopathy[J].Cell Death Dis,2014,5(10):e1479.
[44] Mohr S,Xi X,Tang J,Kern TS .Caspase activation in retinas of diabetic and galactosemic mice and diabetic patients[J].Diabetes,2002,4(51):1172-1179.
[45] Kerur N,Fukuda S,Banerjee D,et al.cGAS drives non-canonical inflammasome activation in age-related macular degeneration[J].Nat Med,2017,24(1):50-61.
[46] Dihlmann S,Erhart P,Mehrabi A,et al.Increased expression and activation of absent in melanoma 2 inflammasome components in lymphocytic infiltrates of abdominal aortic aneurysms[J].Mol Med,2014,19(20):230-237.
[47] Kang R,Zeng L,Zhu S,et al.Lipid peroxidation drives gasdermin d-mediated pyroptosis in lethal polymicrobial sepsis[J].Cell Host Microbe,2018,24(1):97-108.
[2] Iskandar R,Liu S,Xiang F,et al.Expression of pericardial fluid T-cells and related inflammatory cytokines in patients with chronic heart failure [J].Exp Ther Med,2017,5(13):1850-1858.
[3] Ridker PM,Cushman M,Stampfer MJ,et al.Inflammation,aspirin,and the risk of cardiovascular disease in apparently healthy men[J].N Engl J Med,1997,336(14):973-979.
[4] Ridker PM,Hennekens CH,Buring JE,et al.C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women[J].N Engl J Med,2000,342(12):836-843.
[5] Everett BM,Pradhan AD,Solomon DH,et al.Rationale and design of the cardiovascular inflammation reduction trial:a test of the inflammatory hypothesis of atherothrombosis[J].Am Heart J,2013,166(2):199-207.
[6] Ridker PM,Thuren T,Zalewski A,et al.Interleukin-1beta inhibition and the prevention of recurrent cardiovascular events:rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS)[J].Am Heart J,2011,162(4):597-605.
[7] Hudson BI,Lippman ME.Targeting RAGE signaling in inflammatory disease[J].Annu Rev Med,2018,69:349-364.
[8] Chen X,Cui R,Li R,et al.Development of pristane induced mice model for lupus with atherosclerosis and analysis of TLR expression[J].Clin Exp Rheumatol,2016,34(4):600-608.
[9] Zhou W,Chen C,Chen Z,et al.NLRP3:a novel mediator in cardiovascular disease[J].J Immunol Res,2018,2018:5702103.
[10] Shalini S,Dorstyn L,Dawar S,et al.Old,new and emerging functions of caspases[J].Cell Death Differ,2015,22(4):526-539.
[11] Saleh M,Vaillancourt JP,Graham RK,et al.Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms[J].Nature,2004,6987(429):75-79.
[12] Man SM,Karki R,Kanneganti T.Molecular mechanisms and functions of pyroptosis,inflammatory caspases and inflammasomes in infectious diseases[J].Immunological Reviews,2017,277(1):61-75.
[13] He WT,Wan H,Hu L,et al.Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion[J].Cell Res,2015,12(25):1285-1298.
[14] Merkle S,Frantz S,Schon MP,et al.A role for caspase-1 in heart failure[J].Circ Res,2007,100(5):645-653.
[15] Burgeiro A,Fonseca AC,Espinoza D,et al.Proteostasis in epicardial versus subcutaneous adipose tissue in heart failure subjects with and without diabetes[J].Biochim Biophys Acta Mol Basis Dis,2018,1864(6PtA):2183-2198.
[16] Mann DL.Innate immunity and the failing heart:the cytokine hypothesis revisited[J].Circ Res,2015,116(7):1254-1268.
[17] Van Tassell BW,Arena R,Biondi-Zoccai G,et al.Effects of interleukin-1 blockade with anakinra on aerobic exercise capacity in patients with heart failure and preserved ejection fraction (from the D-HART Pilot Study)[J].Am J Cardiol,2013,113(2):321-327.
[18] Van Tassell BW,Abouzaki NA,Oddi Erdle C,et al.Interleukin-1 blockade in acute decompensated heart failure:a randomized,double-blinded,placebo-controlled pilot study[J].J Cardiovasc Pharmacol,2016,67(6):544-551.
[19] Toldo S,Abbate A.The NLRP3 inflammasome in acute myocardial infarction[J].Nat Rev Cardiol,2018,15(4):203-214.
[20] Aries A,Whitcomb J,Shao W,et al.Caspase-1 cleavage of transcription factor GATA4 and regulation of cardiac cell fate[J].Cell Death Dis,2014,5(12):e1566.
[21] Lee S,Choi E,Cha M,et al.Looking for pyroptosis-modulating miRNAs as a therapeutic target for improving myocardium survival[J].Mediators Inflamm,2015,2015:1-8.
[22] Yang F,Qin Y,Wang Y,et al.LncRNA KCNQ1OT1 mediates pyroptosis in diabetic cardiomyopathy[J].Cell Physiol Biochem,2018,50(4):1230-1244.
[23] Dwaich KH,Al-Amran FG,Al-Sheibani BI,et al.Melatonin effects on myocardial ischemia-reperfusion injury:impact on the outcome in patients undergoing coronary artery bypass grafting surgery[J].Int J Cardiol,2016,221:977-986.
[24] Kawaguchi M,Takahashi M,Hata T,et al.Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia/reperfusion injury[J].Circulation,2011,123(6):594-604.
[25] Wang M,Tsai BM,Kher A,et al.Role of endogenous testosterone in myocardial proinflammatory and proapoptotic signaling after acute ischemia-reperfusion[J].Am J Physiol Heart Circ Physiol,2005,288(1):H221-H226.
[26] Audia JP,Yang XM,Crockett ES,et al.Caspase-1 inhibition by VX-765 administered at reperfusion in P2Y12 receptor antagonist-treated rats provides long-term reduction in myocardial infarct size and preservation of ventricular function[J].Basic Res Cardiol,2018,113(5):32.
[27] Frantz S,Ducharme A,Sawyer D,et al.Targeted deletion of caspase-1 reduces early mortality and left ventricular dilatation following myocardial infarction[J].J Mol Cell Cardiol,2003,35(6):685-694.
[28] 廖端芳,龚勇珍,孙少卫.细胞炎症反应与脂质代谢的相互作用及调节[J].中国动脉硬化杂志,2017,25(6):623-629.
[29] Zheng F,Gong Z,Xing S,et al.Overexpression of caspase-1 in aorta of patients with coronary atherosclerosis[J].Heart Lung Circ,2014,23(11):1070-1074.
[30] Usui F,Shirasuna K,Kimura H,et al.Critical role of caspase-1 in vascular inflammation and development of atherosclerosis in Western diet-fed apolipoprotein E-deficient mice[J].Biochem Biophysical Res Commun,2012,425(2):162-168.
[31] Gage J,Hasu M,Thabet M,et al.Caspase-1 deficiency decreases atherosclerosis in apolipoprotein e-null mice[J].Canad J Cardiol,2012,28(2):222-229.
[32] Hendrikx T,Jeurissen ML,van Gorp PJ,et al.Bone marrow-specific caspase-1/11 deficiency inhibits atherosclerosis development in LDLR(-/-) mice[J].FEBS J,2015,282(12):2327-2338.
[33] Chang W,Lin J,Dong J,et al.Pyroptosis:an inflammatory cell death implicates in atherosclerosis[J].Med Hypoth,2013,81(3):484-486.
[34] Xu YJ,Zheng L,Hu YW,et al.Pyroptosis and its relationship to atherosclerosis[J].Clin Chim Acta,2018,476:28-37.
[35] Doi T,Doi S,Nakashima A,et al.Mizoribine ameliorates renal injury and hypertension along with the attenuation of renal caspase-1 expression in aldosterone-salt-treated rats[J].PLoS One,2014,9(4):e93513.
[36] Qi J,Yu X,Shi X,et al.NF-κB blockade in hypothalamic paraventricular nucleus inhibits high-salt-induced hypertension through NLRP3 and caspase-1[J].Cardiovasc Toxicol,2016,16(4):345-354.
[37] Krishnan SM,Sobey CG,Latz E,et al.IL-1beta and IL-18:inflammatory markers or mediators of hypertension?[J].Br J Pharmacol,2014,171(24):5589-5602.
[38] Martelli A,Testai L,Anzini M,et al.The novel anti-inflammatory agent VA694,endowed with both NO-releasing and COX2-selective inhibiting properties,exhibits NO-mediated positive effects on blood pressure,coronary flow and endothelium in an experimental model of hypertension and endothelial dysfunction[J].Pharmacol Res,2013,78:1-9.
[39] Pasqua T,Pagliaro P,Rocca C,et al.Role of NLRP-3 inflammasome in hypertension:a potential therapeutic target[J].Curr Pharm Biotechnol,2018,19(9):708-714 .
[40] 阿希,李玉琳,王绿娅,等.炎症小体Nlrp3在高血压小鼠心肌纤维化中的作用[J].心肺血管病杂志,2015,34(6):496-500.
[41] Yin J,You S,Liu H,et al.Role of P2X7R in the development and progression of pulmonary hypertension[J].Respir Res,2017,18(1):127.
[42] Takahashi M.NLRP3 Inflammasome as a novel player in myocardial infarction[J].Int Heart J,2014,55(2):101-105.
[43] Li X,Du N,Zhang Q,et al.MicroRNA-30d regulates cardiomyocyte pyroptosis by directly targeting foxo3a in diabetic cardiomyopathy[J].Cell Death Dis,2014,5(10):e1479.
[44] Mohr S,Xi X,Tang J,Kern TS .Caspase activation in retinas of diabetic and galactosemic mice and diabetic patients[J].Diabetes,2002,4(51):1172-1179.
[45] Kerur N,Fukuda S,Banerjee D,et al.cGAS drives non-canonical inflammasome activation in age-related macular degeneration[J].Nat Med,2017,24(1):50-61.
[46] Dihlmann S,Erhart P,Mehrabi A,et al.Increased expression and activation of absent in melanoma 2 inflammasome components in lymphocytic infiltrates of abdominal aortic aneurysms[J].Mol Med,2014,19(20):230-237.
[47] Kang R,Zeng L,Zhu S,et al.Lipid peroxidation drives gasdermin d-mediated pyroptosis in lethal polymicrobial sepsis[J].Cell Host Microbe,2018,24(1):97-108.