p53信号通路在心力衰竭中的作用机制
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摘要
<正>心力衰竭是各种原因导致的心脏收缩和/或舒张功能失常,心脏泵血功能障碍,同时也是多种心血管疾病的终末阶段,具有非常高的患病率和病死率[1],成为引起死亡的主要原因之一。据临床调查显示,有临床症状的心力衰竭患者其5年生存率与恶性肿瘤基本相似。心室重构是心力衰竭发生、发展的基本机制之一。在重构的过程中,p53信号通路被激活,能够诱导心肌细胞凋亡,是心力衰竭从代偿走向失代偿的转折点。
引文
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[32]Ingwall JS,Weiss RG.Is the failing heart energy starved on using chemical energy to support cardiac function[J].Circ Res,2004,95(2):135-145
[33]Stanley WC,Recchia FA,Lopaschuk GD,et al.Myocardial substrate metabolism in the normal and failing heart[J].Physiol Rev,2005,85(3):1093-1129
[34]Lopaschuk GD,Ussher JR,Folmes CD,et al.Myocardial fatty acid metabolism in health and disease[J].Physiol Rev,2010,90(1):207-258
[35]Tian R,Nascimben L,Kaddurah-Daouk R,et al.Depletion of energy reserve via the creatine kinase reaction during the evolution of heart failure in cardiomyopathic hamsters[J].Mol Cell Cardiol,1996,28(4):755-765
[36]Osorio JC,Stanley WC,Linke A,et al.Impaired myocardial fatty acid oxidation and reduced protein expression of retinoid x receptor-alpha in pacing-induced heart failure[J].Circulation,2002,106(5):606-612
[37] Ott M,Gogvadze V,Orrenius S,et al.Mitochondria,oxidative stress and cell death[J].Apoptosis,2007,12(5):913-922
[38]Marchenko ND,Zaika A,Moll UM,et al.Death signal-induced localization of p53protein to mitochondria:apotential role in apoptotic signaling[J].Biol Chem,2000,275(21):16202-16212
[39]Schuler M,Bossy-Wetzel E,Goldstein JC,et al.p53 induces apoptosis by caspase activation through mitochondrial cytochrome c release[J].Biol Chem,2000,275(10):7337-7342
[40]Hoshino A,Mita Y,Okawa Y,et al.Cytosolic p53inhibits parkin-mediated mitophagy and promotes mitochondrial dysfunction in the mouse heart[J].Nat Commun,2013,4:2308
[41]Kimata M,Matoba S,Iwai-Kanai E,et al.p53and TIGAR regulate cardiac myocyte energy homeostasis under hypoxic stress[J].Am J Physiol Heart Circ Physiol,2010,299(6):H1908-1916
[42] Morisco C,Zebrowski D,Condorelli G,et al.The Akt-glycogen synthase kinase 3beta pathwayregulates transcription of atrial natriuretic factor induced by betaadrenergic receptor stimulation in cardiac myocytes[J].Biol Chem,2000,275(19):14466-14475
[43]Schwartzbauer G,Robbins J.The tumor suppressor gene PTEN can regulate cardiac hypertrophy and survival[J].Biol Chem,2001,276(38):35786-35793
[44]Toth A,Nickson P,Qin LL,et al.Differential regulation of cardiomyocyte survival and hypertrophy by MDM2,an E3ubiquitin ligase[J].Biol Chem,2006,281(6):3679-3689
[45]Naito AT,Okada S,Minamino T,et al.Promotion of CHIP mediated p53degradation protects the heart from ischemic injury[J].Circ Res,2010,106(11):1692-1702
[46]Song H,Conte JV Jr,Foster AH,et al.Increased p53protein expression in human failingmyocardium[J].Heart Lung Transplant,1999,18(8):744-749
[2]Chang H,Li C,Wang Q,et al.QSKL protects against myocardial apoptosis on heart failure lia PBK/Akt-p53signaling pathway[J].Scientific reports,2017,7(1):16986
[3]Long X,Boluyt MO,Hipolito ML,et al.p53and the hypoxia-induced apoptosis of cultured neonatal rat cardiac myocytes[J].Clin Invest,1997,99(11):2635-2643
[4]Xie Z,Koyama T,Abe K,et al.Upregulation of P53protein in rat heart subjected to a transient occlusion of the coronary artery followed by reperfusion[J].Jpn J Physiol,2000,50(1):159-162
[5]Gogiraju R,Xu X,Bochenek ML,et al.Endothelial p53deletion improves angiogenesis and prevents cardiac fibrosis and heart failureinduced by pressureoverload in mice[J].Am Heart Assoc,2015,4(2):e001770
[6]Zhang Y,Kohler K,Xu J,et al.Inhibition of p53after acute myocardial infarction:reduction of apoptosis is counteracted by disturbed scar formation and cardiac rupture[J].Mol Cell Cardiol,2011,50(3):471-478
[7]Chen QM,Tu VC.Apoptosis and heart failure:mechanisms and therapeuticimplications[J].AM J Cardiovasc Drugs,2002,2(1):43-57
[8]Sheikh MS,Fornace AJ.Role of p53family members in apoptosis[J].Cell Physiol,2000,182(2):171-181
[9]Birks EJ,Latif N,Enesa K,et al.Elevated p53expression is associated with dysregulation of the ubiquitin-proteasome system in dilated cardiomyopathy[J].Cardiovasc Res,2008,79(3):472-480
[10]Tsukamoto O,Minamino T,Okada K,et al.Depression of proteasome activities during the progression of cardiac dysfunction in pressureoverloaded heart of mice[J].Biochem Biophys Res Commun,2006,340(4):1125-1133
[11]Tirziu D,Chorianopoulos E,Moodie KL,et al.Myocardial hypertrophy in the absence of external stimuli is induced by angiogenesis in mice[J].J Clin Invest,2007,117(11):3188-3197
[12]Liu X,Chua CC,Gao J,et al.Pifithrin-alpha protects against doxorubicin-induced apoptosis and acute cardiotoxicity in mice[J].Am J Physiol Heart Circ Physiol,2004,286(3):H933-H939
[13]Shizukuda Y,Matoba S,Mian OY,et al.Targeteddisruption of p53attenuates doxorubicin-induced cardiac toxicity in mice[J].Mol Cell Biochem,2005,273(1-2):25-32
[14]Das B,Young D,Vasanji A,et al.Influence of p53in the transition of myotrophin-induced cardiac hypertrophy to heartfailure[J].Cardiovasc Res,2010,87(3):524-534
[15]Chatterjee A,Mir SA.Dutta D,et al.Analysis of p53and NF-κB signaling in modulating the cardiomyocytefate during hypertrophy[J].Cell Physiol,2011,226(10):2543-2354
[16]Toko H,Takahashi H,Kayama Y,et al.MDCa2+/Calmodulin-dependent kinase IIδcauses heart failure by accumulation of p53in dilated cardiomyopathy[J].Circulation,2010,122(9):891-899
[17]Regula KM,Kirshenbaum LA.p53activates the mitochondrial death pathway and apoptosis of ventricular myocytes independent of de novo gene transcription[J].Mol Cell Cardiol,2001,33(8):1435-1445
[18]Xiong S,Van Pelt CS,Elizondo-Fraire AC,et al.Loss of Mdm4results in p53-dependent dilated cardiomyopathy[J].Circulation,2007,115(23):2925-2930
[19]Oskarsson HJ,Coppey L,Weiss RM,et al.Antioxidants attenuate myocyte apoptosis in the remote non-infarcted myocardium following large myocardial infarction[J].Cardiovasc Res,2000,45(3):679-687
[20]Sun A,Zou Y,Wang P,et al.Mitochondrial aldehyde dehydrogenase 2plays protective roles in heart failure after myocardial infarction via suppression of the cytosolic JNK/p53pathway in mice[J].Am Heart Assoc,2014,3(5):e000779
[21]Oka T,Akazawa H,Naito AT,et al.Angiogenesis and cardiac hypertrophy.Maintenance of cardiac function and causative roles in heart failure[J].Circ Res,2014,114(3):565-571
[22]Jimenez B,Volpert OV,Crawford SE,et al.Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1[J].Nat Med,2000,6(1):41-48
[23]Spyridopoulos I,Brogi E,Kearney M,et al.Vascular endothelial growth factor inhibits endothelial cell apoptosis induced by tumor necrosis factor-alpha:balance between growth and death signals[J].Mol Cell Cardiol,1997,29(5):1321-1330
[24]Masuda T,Muto S,Fujisawa G,et al.Heart angiotensin II-induced cardiomyocyte hypertrophy suppresses coronary angiogenesis and progresses diabetic cardiomyopathy[J].Am J Physiol Heart Circ Physiol,2012,302(9):H1871-1883
[25]Sano M,Minamino T,Toko H,et al.p53-induced inhibition of Hif-1causes cardiac dysfunction during pressure overload[J].Nature,2007,446(7134):444-448
[26]Guan A,Gong H,Ye Y,et al.Regulation of p53by jagged1 contributes to angiotensin II-induced impairment of myocardial angiogenesis[J].PLOS One,2013,8(10):e76529
[27]Shimizu I,Yoshida Y,Katsuno T,et al.Adipose tissue inflammation in diabetes and heart failure[J].Microbes Infect,2013,15(1):11-17
[28]Shimizu I,Yoshida Y,Katsuno T,et al.p53-induced adipose tissue inflammation is critically involved in the development of insulin resistance in heart failure[J].Cell Metab,2012,15(1):51-64
[29]Zhou SF,Yuan J,Liao MY,et al.IL-17Apromotes ventricular remodeling after myocardial infarction[J].Mol Med(Berl),2014,92(10):1105-1116
[30]Tamaki Y,Iwanaga Y,Niizuma S,et al.Metastasis-associated protein,S100A4 mediates cardiac fibrosis potentially through the modulation of p53in cardiac fibroblasts[J].Mol Cell Cardiol,2013,57:72-81
[31]戚晓琳,韩继召,董娴宁,等.S100A4和p53蛋白在肥厚型心肌病心肌纤维化中的表达及意义[J].中国医药导报,2015,12(35):44-47
[32]Ingwall JS,Weiss RG.Is the failing heart energy starved on using chemical energy to support cardiac function[J].Circ Res,2004,95(2):135-145
[33]Stanley WC,Recchia FA,Lopaschuk GD,et al.Myocardial substrate metabolism in the normal and failing heart[J].Physiol Rev,2005,85(3):1093-1129
[34]Lopaschuk GD,Ussher JR,Folmes CD,et al.Myocardial fatty acid metabolism in health and disease[J].Physiol Rev,2010,90(1):207-258
[35]Tian R,Nascimben L,Kaddurah-Daouk R,et al.Depletion of energy reserve via the creatine kinase reaction during the evolution of heart failure in cardiomyopathic hamsters[J].Mol Cell Cardiol,1996,28(4):755-765
[36]Osorio JC,Stanley WC,Linke A,et al.Impaired myocardial fatty acid oxidation and reduced protein expression of retinoid x receptor-alpha in pacing-induced heart failure[J].Circulation,2002,106(5):606-612
[37] Ott M,Gogvadze V,Orrenius S,et al.Mitochondria,oxidative stress and cell death[J].Apoptosis,2007,12(5):913-922
[38]Marchenko ND,Zaika A,Moll UM,et al.Death signal-induced localization of p53protein to mitochondria:apotential role in apoptotic signaling[J].Biol Chem,2000,275(21):16202-16212
[39]Schuler M,Bossy-Wetzel E,Goldstein JC,et al.p53 induces apoptosis by caspase activation through mitochondrial cytochrome c release[J].Biol Chem,2000,275(10):7337-7342
[40]Hoshino A,Mita Y,Okawa Y,et al.Cytosolic p53inhibits parkin-mediated mitophagy and promotes mitochondrial dysfunction in the mouse heart[J].Nat Commun,2013,4:2308
[41]Kimata M,Matoba S,Iwai-Kanai E,et al.p53and TIGAR regulate cardiac myocyte energy homeostasis under hypoxic stress[J].Am J Physiol Heart Circ Physiol,2010,299(6):H1908-1916
[42] Morisco C,Zebrowski D,Condorelli G,et al.The Akt-glycogen synthase kinase 3beta pathwayregulates transcription of atrial natriuretic factor induced by betaadrenergic receptor stimulation in cardiac myocytes[J].Biol Chem,2000,275(19):14466-14475
[43]Schwartzbauer G,Robbins J.The tumor suppressor gene PTEN can regulate cardiac hypertrophy and survival[J].Biol Chem,2001,276(38):35786-35793
[44]Toth A,Nickson P,Qin LL,et al.Differential regulation of cardiomyocyte survival and hypertrophy by MDM2,an E3ubiquitin ligase[J].Biol Chem,2006,281(6):3679-3689
[45]Naito AT,Okada S,Minamino T,et al.Promotion of CHIP mediated p53degradation protects the heart from ischemic injury[J].Circ Res,2010,106(11):1692-1702
[46]Song H,Conte JV Jr,Foster AH,et al.Increased p53protein expression in human failingmyocardium[J].Heart Lung Transplant,1999,18(8):744-749