nach oben

Erschienen in:

01.12.2021 | Original Contribution

Single-cell transcriptomic identified HIF1A as a target for attenuating acute rejection after heart transplantation

verfasst von: Yuan Chang, Xiangjie Li, Qi Cheng, Yiqing Hu, Xiao Chen, Xiumeng Hua, Xuexin Fan, Menghao Tao, Jiangping Song, Shengshou Hu

Erschienen in: Basic Research in Cardiology | Ausgabe 1/2021

Einloggen, um Zugang zu erhalten

Abstract

Acute rejection (AR) is an important contributor to graft failure, which remains a leading cause of death after heart transplantation (HTX). The regulation of immune metabolism has become a new hotspot in the development of immunosuppressive drugs. In this study, Increased glucose metabolism of cardiac macrophages was found in patients with AR. To find new therapeutic targets of immune metabolism regulation for AR, CD45⁺ immune cells extracted from murine isografts, allografts, and untransplanted donor hearts were explored by single-cell RNA sequencing. Total 20 immune cell subtypes were identified among 46,040 cells. The function of immune cells in AR were illustrated simultaneously. Cardiac resident macrophages were substantially replaced by monocytes and proinflammatory macrophages during AR. Monocytes/macrophages in AR allograft were more active in antigen presentation and inflammatory recruitment ability, and glycolysis. Based on transcription factor regulation analysis, we found that the increase of glycolysis in monocytes/macrophages was mainly regulated by HIF1A. Inhibition of HIF1A could alleviate inflammatory cells infiltration in AR. To find out the effect of HIF1A on AR, CD45⁺ immune cells extracted from allografts after HIF1A inhibitor treatment were explored by single-cell RNA sequencing. HIF1A inhibitor could reduce the antigen presenting ability and pro-inflammatory ability of macrophages, and reduce the infiltration of Cd4+ and Cd8a+ T cells in AR. The expression of Hif1α in AR monocytes/macrophages was regulated by pyruvate kinase 2. Higher expression of HIF1A in macrophages was also detected in human hearts with AR. These indicated HIF1A may serve as a potential target for attenuating AR.

Nur mit Berechtigung zugänglich

Aibar S, González-Blas CB, Moerman T, Huynh-Thu VA, Imrichova H, Hulselmans G, Rambow F, Marine JC, Geurts P, Aerts J, van den Oord J, Atak ZK, Wouters J, Aerts S (2017) SCENIC: single-cell regulatory network inference and clustering. Nat Methods 14:1083–1086. https://doi.org/10.1038/nmeth.4463CrossRefPubMedPubMedCentral

Alves-Filho JC, Pålsson-McDermott EM (2016) Pyruvate kinase M2: a potential target for regulating inflammation. Front Immunol 7:145. https://doi.org/10.3389/fimmu.2016.00145CrossRefPubMedPubMedCentral

Bao M, Wang Y, Liu Y, Shi P, Lu H, Sha W, Weng L, Hanabuchi S, Qin J, Plumas J, Chaperot L, Zhang Z, Liu YJ (2016) NFATC3 promotes IRF7 transcriptional activity in plasmacytoid dendritic cells. J Exp Med 213:2383–2398. https://doi.org/10.1084/jem.20160438CrossRefPubMedPubMedCentral

Brewitz A, Eickhoff S, Dähling S, Quast T, Bedoui S, Kroczek RA, Kurts C, Garbi N, Barchet W, Iannacone M, Klauschen F, Kolanus W, Kaisho T, Colonna M, Germain RN, Kastenmüller W (2017) CD8(+) T cells orchestrate pDC-XCR1(+) dendritic cell spatial and functional cooperativity to optimize priming. Immunity 46:205–219. https://doi.org/10.1016/j.immuni.2017.01.003CrossRefPubMedPubMedCentral

Cai Z, Manalo DJ, Wei G, Rodriguez ER, Fox-Talbot K, Lu H, Zweier JL, Semenza GL (2003) Hearts from rodents exposed to intermittent hypoxia or erythropoietin are protected against ischemia–reperfusion injury. Circulation 108:79–85. https://doi.org/10.1161/01.Cir.0000078635.89229.8aCrossRefPubMed

Chen X, Dong S, Zhang N, Chen L, Li MG, Yang PC, Song J (2017) MicroRNA-98 plays a critical role in experimental myocarditis. Int J Cardiol 229:75–81. https://doi.org/10.1016/j.ijcard.2016.11.263CrossRefPubMed

Cheng SC, Quintin J, Cramer RA, Shepardson KM, Saeed S, Kumar V, Giamarellos-Bourboulis EJ, Martens JH, Rao NA, Aghajanirefah A, Manjeri GR, Li Y, Ifrim DC, Arts RJ, van der Veer BM, Deen PM, Logie C, O’Neill LA, Willems P, van de Veerdonk FL, van der Meer JW, Ng A, Joosten LA, Wijmenga C, Stunnenberg HG, Xavier RJ, Netea MG (2014) mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science 345:1250684. https://doi.org/10.1126/science.1250684CrossRefPubMedPubMedCentral

Corcoran SE, O’Neill LA (2016) HIF1α and metabolic reprogramming in inflammation. J Clin Investig 126:3699–3707. https://doi.org/10.1172/jci84431CrossRefPubMedPubMedCentral

Crespo-Leiro MG, Metra M, Lund LH, Milicic D, Costanzo MR, Filippatos G, Gustafsson F, Tsui S, Barge-Caballero E, De Jonge N, Frigerio M, Hamdan R, Hasin T, Hulsmann M, Nalbantgil S, Potena L, Bauersachs J, Gkouziouta A, Ruhparwar A, Ristic AD, Straburzynska-Migaj E, McDonagh T, Seferovic P, Ruschitzka F (2018) Advanced heart failure: a position statement of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 20:1505–1535. https://doi.org/10.1002/ejhf.1236CrossRefPubMed

10.

Cuesta-Mateos C, Portero-Sainz I, García-Peydró M, Alcain J, Fuentes P, Juárez-Sánchez R, Pérez-García Y, Mateu-Albero T, Díaz-Fernández P, Vega-Piris L, Sánchez-López BA, Marcos-Jiménez A, Cardeñoso L, Gómez-García de Soria V, Toribio ML, Muñoz-Calleja C (2020) Evaluation of therapeutic targeting of CCR7 in acute graft-versus-host disease. Bone Marrow Transplant 55:1935–1945. https://doi.org/10.1038/s41409-020-0830-8CrossRefPubMed

11.

Dai H, Lan P, Zhao D, Abou-Daya K, Liu W, Chen W, Friday AJ, Williams AL, Sun T, Chen J, Chen W, Mortin-Toth S, Danska JS, Wiebe C, Nickerson P, Li T, Mathews LR, Turnquist HR, Nicotra ML, Gingras S, Takayama E, Kubagawa H, Shlomchik MJ, Oberbarnscheidt MH, Li XC, Lakkis FG (2020) PIRs mediate innate myeloid cell memory to nonself MHC molecules. Science 368:1122–1127. https://doi.org/10.1126/science.aax4040CrossRefPubMedPubMedCentral

12.

Farbehi N, Patrick R, Dorison A, Xaymardan M, Janbandhu V, Wystub-Lis K, Ho JW, Nordon RE, Harvey RP (2019) Single-cell expression profiling reveals dynamic flux of cardiac stromal, vascular and immune cells in health and injury. Elife. https://doi.org/10.7554/eLife.43882CrossRefPubMedPubMedCentral

13.

He R, Hou S, Liu C, Zhang A, Bai Q, Han M, Yang Y, Wei G, Shen T, Yang X, Xu L, Chen X, Hao Y, Wang P, Zhu C, Ou J, Liang H, Ni T, Zhang X, Zhou X, Deng K, Chen Y, Luo Y, Xu J, Qi H, Wu Y, Ye L (2016) Follicular CXCR5- expressing CD8(+) T cells curtail chronic viral infection. Nature 537:412–428. https://doi.org/10.1038/nature19317CrossRefPubMed

14.

Huang X, Feng Z, Jiang Y, Li J, Xiang Q, Guo S, Yang C, Fei L, Guo G, Zheng L, Wu Y, Chen Y (2019) VSIG4 mediates transcriptional inhibition of Nlrp3 and Il-1β in macrophages. Sci Adv 5:eaau7426. https://doi.org/10.1126/sciadv.aau7426CrossRefPubMedPubMedCentral

15.

Hulsmans M, Clauss S, Xiao L, Aguirre AD, King KR, Hanley A, Hucker WJ, Wülfers EM, Seemann G, Courties G, Iwamoto Y, Sun Y, Savol AJ, Sager HB, Lavine KJ, Fishbein GA, Capen DE, Da Silva N, Miquerol L, Wakimoto H, Seidman CE, Seidman JG, Sadreyev RI, Naxerova K, Mitchell RN, Brown D, Libby P, Weissleder R, Swirski FK, Kohl P, Vinegoni C, Milan DJ, Ellinor PT, Nahrendorf M (2017) Macrophages facilitate electrical conduction in the heart. Cell 169:510-522.e520. https://doi.org/10.1016/j.cell.2017.03.050CrossRefPubMedPubMedCentral

16.

Keränen MA, Nykänen AI, Krebs R, Pajusola K, Tuuminen R, Alitalo K, Lemström KB (2010) Cardiomyocyte-targeted HIF-1alpha gene therapy inhibits cardiomyocyte apoptosis and cardiac allograft vasculopathy in the rat. J Heart Lung Transplant 29:1058–1066. https://doi.org/10.1016/j.healun.2010.05.021CrossRefPubMed

17.

Keränen MA, Tuuminen R, Syrjälä S, Krebs R, Walkinshaw G, Flippin LA, Arend M, Koskinen PK, Nykänen AI, Lemström KB (2013) Differential effects of pharmacological HIF preconditioning of donors versus recipients in rat cardiac allografts. Am J Transplant 13:600–610. https://doi.org/10.1111/ajt.12064CrossRefPubMed

18.

Kimura A, Rieger MA, Simone JM, Chen W, Wickre MC, Zhu BM, Hoppe PS, O’Shea JJ, Schroeder T, Hennighausen L (2009) The transcription factors STAT5A/B regulate GM-CSF-mediated granulopoiesis. Blood 114:4721–4728. https://doi.org/10.1182/blood-2009-04-216390CrossRefPubMedPubMedCentral

19.

Lauvau G, Chorro L, Spaulding E, Soudja SMH (2014) Inflammatory monocyte effector mechanisms. Cell Immunol 291:32–40. https://doi.org/10.1016/j.cellimm.2014.07.007CrossRefPubMedPubMedCentral

20.

Li J, Diao B, Guo S, Huang X, Yang C, Feng Z, Yan W, Ning Q, Zheng L, Chen Y, Wu Y (2017) VSIG4 inhibits proinflammatory macrophage activation by reprogramming mitochondrial pyruvate metabolism. Nat Commun 8:1322. https://doi.org/10.1038/s41467-017-01327-4CrossRefPubMedPubMedCentral

21.

Liban TJ, Medina EM, Tripathi S, Sengupta S, Henry RW, Buchler NE, Rubin SM (2017) Conservation and divergence of C-terminal domain structure in the retinoblastoma protein family. Proc Natl Acad Sci USA 114:4942–4947. https://doi.org/10.1073/pnas.1619170114CrossRefPubMedPubMedCentral

22.

Litviňuková M, Talavera-López C, Maatz H, Reichart D, Worth CL, Lindberg EL, Kanda M, Polanski K, Heinig M, Lee M, Nadelmann ER, Roberts K, Tuck L, Fasouli ES, DeLaughter DM, McDonough B, Wakimoto H, Gorham JM, Samari S, Mahbubani KT, Saeb-Parsy K, Patone G, Boyle JJ, Zhang H, Zhang H, Viveiros A, Oudit GY, Bayraktar OA, Seidman JG, Seidman CE, Noseda M, Hubner N, Teichmann SA (2020) Cells of the adult human heart. Nature 588:466–472. https://doi.org/10.1038/s41586-020-2797-4CrossRefPubMedPubMedCentral

23.

Liu L, Lu Y, Martinez J, Bi Y, Lian G, Wang T, Milasta S, Wang J, Yang M, Liu G, Green DR, Wang R (2016) Proinflammatory signal suppresses proliferation and shifts macrophage metabolism from Myc-dependent to HIF1α-dependent. Proc Natl Acad Sci USA 113:1564–1569. https://doi.org/10.1073/pnas.1518000113CrossRefPubMedPubMedCentral

24.

Lund LH, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dipchand AI, Dobbels F, Goldfarb SB, Levvey BJ, Meiser B, Yusen RD, Stehlik J (2014) The registry of the International Society for Heart and Lung Transplantation: thirty-first official adult heart transplant report—2014; focus theme: retransplantation. J Heart Lung Transplant 33:996–1008. https://doi.org/10.1016/j.healun.2014.08.003CrossRefPubMed

25.

Maenosono R, Nian Y, Iske J, Liu Y, Minami K, Rommel T, Martin F, Abdi R, Azuma H, Rosner BA, Zhou H, Milford E, Elkhal A, Tullius SG (2021) Recipient sex and estradiol levels affect transplant outcomes in an age-specific fashion. Am J Transplant 21:3239–3255. https://doi.org/10.1111/ajt.16611CrossRefPubMed

26.

Malone AF, Humphreys BD (2019) Single-cell transcriptomics and solid organ transplantation. Transplantation 103:1776–1782. https://doi.org/10.1097/TP.0000000000002725CrossRefPubMedPubMedCentral

27.

McKay D, Shigeoka A, Rubinstein M, Surh C, Sprent J (2006) Simultaneous deletion of MyD88 and Trif delays major histocompatibility and minor antigen mismatch allograft rejection. Eur J Immunol 36:1994–2002. https://doi.org/10.1002/eji.200636249CrossRefPubMed

28.

McNerney ME, Lee KM, Zhou P, Molinero L, Mashayekhi M, Guzior D, Sattar H, Kuppireddi S, Wang CR, Kumar V, Alegre ML (2006) Role of natural killer cell subsets in cardiac allograft rejection. Am J Transplant 6:505–513. https://doi.org/10.1111/j.1600-6143.2005.01226.xCrossRefPubMed

29.

Moffatt SD, Metcalfe SM (2000) Comparison between tacrolimus and cyclosporine as immunosuppressive agents compatible with tolerance induction by CD4/CD8 blockade. Transplantation 69:1724–1726. https://doi.org/10.1097/00007890-200004270-00033CrossRefPubMed

30.

Murphy SP, Porrett PM, Turka LA (2011) Innate immunity in transplant tolerance and rejection. Immunol Rev 241:39–48. https://doi.org/10.1111/j.1600-065X.2011.01009.xCrossRefPubMed

31.

O’Neill LA, Kishton RJ, Rathmell J (2016) A guide to immunometabolism for immunologists. Nat Rev Immunol 16:553–565. https://doi.org/10.1038/nri.2016.70CrossRefPubMedPubMedCentral

32.

Ochando J, Ordikhani F, Boros P, Jordan S (2019) The innate immune response to allotransplants: mechanisms and therapeutic potentials. Cell Mol Immunol 16:350–356. https://doi.org/10.1038/s41423-019-0216-2CrossRefPubMedPubMedCentral

33.

Ogawa M, Suzuki J, Hishikari K, Takayama K, Tanaka H, Isobe M (2008) Clarithromycin attenuates acute and chronic rejection via matrix metalloproteinase suppression in murine cardiac transplantation. J Am Coll Cardiol 51:1977–1985. https://doi.org/10.1016/j.jacc.2008.01.050CrossRefPubMed

34.

Palsson-McDermott EM, Curtis AM, Goel G, Lauterbach MA, Sheedy FJ, Gleeson LE, van den Bosch MW, Quinn SR, Domingo-Fernandez R, Johnston DG, Jiang JK, Israelsen WJ, Keane J, Thomas C, Clish C, Vander Heiden M, Xavier RJ, O’Neill LA (2015) Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the warburg effect in LPS-activated macrophages. Cell Metab 21:65–80. https://doi.org/10.1016/j.cmet.2014.12.005CrossRefPubMedPubMedCentral

35.

Raichlin E, Edwards BS, Kremers WK, Clavell AL, Rodeheffer RJ, Frantz RP, Pereira NL, Daly RC, McGregor CG, Lerman A, Kushwaha SS (2009) Acute cellular rejection and the subsequent development of allograft vasculopathy after cardiac transplantation. J Heart Lung Transplant 28:320–327. https://doi.org/10.1016/j.healun.2009.01.006CrossRefPubMed

36.

Ratliff ML, Garton J, Garman L, Barron MD, Georgescu C, White KA, Chakravarty E, Wren JD, Montgomery CG, James JA, Webb CF (2019) ARID3a gene profiles are strongly associated with human interferon alpha production. J Autoimmun 96:158–167. https://doi.org/10.1016/j.jaut.2018.09.013CrossRefPubMed

37.

Rosenbaum S, Kreft S, Etich J, Frie C, Stermann J, Grskovic I, Frey B, Mielenz D, Pöschl E, Gaipl U, Paulsson M, Brachvogel B (2011) Identification of novel binding partners (annexins) for the cell death signal phosphatidylserine and definition of their recognition motif. J Biol Chem 286:5708–5716. https://doi.org/10.1074/jbc.M110.193086CrossRefPubMed

38.

Scozzi D, Ibrahim M, Menna C, Krupnick AS, Kreisel D, Gelman AE (2017) The role of neutrophils in transplanted organs. Am J Transplant 17:328–335. https://doi.org/10.1111/ajt.13940CrossRefPubMed

39.

Seguín-Estévez Q, De Palma R, Krawczyk M, Leimgruber E, Villard J, Picard C, Tagliamacco A, Abbate G, Gorski J, Nocera A, Reith W (2009) The transcription factor RFX protects MHC class II genes against epigenetic silencing by DNA methylation. J Immunol 183:2545–2553. https://doi.org/10.4049/jimmunol.0900376CrossRefPubMed

40.

Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR, Chi H (2011) HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med 208:1367–1376. https://doi.org/10.1084/jem.20110278CrossRefPubMedPubMedCentral

41.

Shirakawa K, Endo J, Kataoka M, Katsumata Y, Yoshida N, Yamamoto T, Isobe S, Moriyama H, Goto S, Kitakata H, Hiraide T, Fukuda K, Sano M (2018) IL (interleukin)-10-STAT3-galectin-3 axis is essential for osteopontin-producing reparative macrophage polarization after myocardial infarction. Circulation 138:2021–2035. https://doi.org/10.1161/circulationaha.118.035047CrossRefPubMed

42.

Silvis MJM, Kaffka Genaamd Dengler SE, Odille CA, Mishra M, van der Kaaij NP, Doevendans PA, Sluijter JPG, de Kleijn DPV, de Jager SCA, Bosch L, van Hout GPJ (2020) Damage-associated molecular patterns in myocardial infarction and heart transplantation: the road to translational success. Front Immunol 11:599511. https://doi.org/10.3389/fimmu.2020.599511CrossRefPubMedPubMedCentral

43.

Siu JHY, Surendrakumar V, Richards JA, Pettigrew GJ (2018) T cell allorecognition pathways in solid organ transplantation. Front Immunol 9:2548. https://doi.org/10.3389/fimmu.2018.02548CrossRefPubMedPubMedCentral

44.

Soderlund C, Ohman J, Nilsson J, Higgins T, Kornhall B, Johansson L, Radegran G (2014) Acute cellular rejection the first year after heart transplantation and its impact on survival: a single-centre retrospective study at Skane University Hospital in Lund 1988–2010. Transpl Int 27:482–492. https://doi.org/10.1111/tri.12284CrossRefPubMed

45.

Souto-Carneiro MM, Klika KD, Abreu MT, Meyer AP, Saffrich R, Sandhoff R, Jennemann R, Kraus FV, Tykocinski LO, Eckstein V, Carvalho L, Kriegsmann M, Giese T, Lorenz HM, Carvalho RA (2020) Proinflammatory profile of autoimmune CD8(+) T cells relies on increased LDHA activity and aerobic glycolysis. Arthritis Rheumatol. https://doi.org/10.1002/art.41420CrossRefPubMed

46.

Stehlik J, Kobashigawa J, Hunt SA, Reichenspurner H, Kirklin JK (2018) Honoring 50 years of clinical heart transplantation in circulation: in-depth state-of-the-art review. Circulation 137:71–87. https://doi.org/10.1161/circulationaha.117.029753CrossRefPubMed

47.

Stuart T, Butler A, Hoffman P, Hafemeister C, Papalexi E, Mauck WM 3rd, Hao Y, Stoeckius M, Smibert P, Satija R (2019) Comprehensive integration of single-cell data. Cell 177:1888-1902.e1821. https://doi.org/10.1016/j.cell.2019.05.031CrossRefPubMedPubMedCentral

48.

Turrel-Davin F, Tournadre A, Pachot A, Arnaud B, Cazalis MA, Mougin B, Miossec P (2010) FoxO3a involved in neutrophil and T cell survival is overexpressed in rheumatoid blood and synovial tissue. Ann Rheum Dis 69:755–760. https://doi.org/10.1136/ard.2009.109991CrossRefPubMed

49.

Tyrakis PA, Palazon A, Macias D, Lee KL, Phan AT, Veliça P, You J, Chia GS, Sim J, Doedens A, Abelanet A, Evans CE, Griffiths JR, Poellinger L, Goldrath AW, Johnson RS (2016) S-2-hydroxyglutarate regulates CD8(+) T-lymphocyte fate. Nature 540:236–241. https://doi.org/10.1038/nature20165CrossRefPubMedPubMedCentral

50.

Webb GJ, Hirschfield GM, Lane PJ (2016) OX40, OX40L and autoimmunity: a comprehensive review. Clin Rev Allergy Immunol 50:312–332. https://doi.org/10.1007/s12016-015-8498-3CrossRefPubMed

51.

Weber BN, Kobashigawa JA, Givertz MM (2017) Evolving areas in heart transplantation. JACC Heart Fail 5:869–878. https://doi.org/10.1016/j.jchf.2017.10.009CrossRefPubMed

52.

Wolock SL, Lopez R, Klein AM (2019) Scrublet: computational identification of cell doublets in single-cell transcriptomic data. Cell Syst 8:281-291.e289. https://doi.org/10.1016/j.cels.2018.11.005CrossRefPubMedPubMedCentral

53.

Wu B, Wang Y, Wang C, Wang GG, Wu J, Wan YY (2016) BPTF is essential for T cell homeostasis and function. J Immunol 197:4325–4333. https://doi.org/10.4049/jimmunol.1600642CrossRefPubMed

54.

Xu C, Zhang C, Ji J, Wang C, Yang J, Geng B, Zhao T, Zhou H, Mu X, Pan J, Hu S, Lv Y, Chen X, Wen H, You Q (2018) CD36 deficiency attenuates immune-mediated hepatitis in mice by modulating the proapoptotic ef. Hepatology (Baltimore, MD) 67:1943–1955. https://doi.org/10.1002/hep.29716CrossRef

55.

Xu T, Stewart KM, Wang X, Liu K, Xie M, Ryu JK, Li K, Ma T, Wang H, Ni L, Zhu S, Cao N, Zhu D, Zhang Y, Akassoglou K, Dong C, Driggers EM, Ding S (2017) Metabolic control of T(H)17 and induced T(reg) cell balance by an epigenetic mechanism. Nature 548:228–233. https://doi.org/10.1038/nature23475CrossRefPubMedPubMedCentral

56.

Zahra K, Dey T, Ashish MSP, Pandey U (2020) Pyruvate kinase M2 and cancer: the role of PKM2 in promoting tumorigenesis. Front Oncol 10:159. https://doi.org/10.3389/fonc.2020.00159CrossRefPubMedPubMedCentral

57.

Zewinger S, Reiser J, Jankowski V, Alansary D, Hahm E, Triem S, Klug M, Schunk SJ, Schmit D, Kramann R, Körbel C, Ampofo E, Laschke MW, Selejan S-R, Paschen A, Herter T, Schuster S, Silbernagel G, Sester M, Sester U, Aßmann G, Bals R, Kostner G, Jahnen-Dechent W, Menger MD, Rohrer L, März W, Böhm M, Jankowski J, Kopf M, Latz E, Niemeyer BA, Fliser D, Laufs U, Speer T (2020) Apolipoprotein C3 induces inflammation and organ damage by alternative inflammasome activation. Nat Immunol 21:30–41. https://doi.org/10.1038/s41590-019-0548-1CrossRefPubMed

58.

Zhang X, Han S, Kang Y, Guo M, Hong S, Liu F, Fu S, Wang L, Wang QX (2012) SAHA, an HDAC inhibitor, synergizes with tacrolimus to prevent murine cardiac allograft rejection. Cell Mol Immunol 9:390–398. https://doi.org/10.1038/cmi.2012.28CrossRefPubMedPubMedCentral

59.

Zhu B, Zhang R, Li C, Jiang L, Xiang M, Ye Z, Kita H, Melnick AM, Dent AL, Sun J (2019) BCL6 modulates tissue neutrophil survival and exacerbates pulmonary inflammation following influenza virus infection. Proc Natl Acad Sci U S A 116:11888–11893. https://doi.org/10.1073/pnas.1902310116CrossRefPubMedPubMedCentral

60.

Zou Y, Steurer W, Klima G, Obrist P, Margreiter R, Brandacher G (2002) Estradiol enhances murine cardiac allograft rejection under cyclosporin and can be antagonized by the antiestrogen tamoxifen. Transplantation 74:354–357. https://doi.org/10.1097/00007890-200208150-00010CrossRefPubMed

Titel: Single-cell transcriptomic identified HIF1A as a target for attenuating acute rejection after heart transplantation
verfasst von: Yuan Chang
Xiangjie Li
Qi Cheng
Yiqing Hu
Xiao Chen
Xiumeng Hua
Xuexin Fan
Menghao Tao
Jiangping Song
Shengshou Hu
Publikationsdatum: 01.12.2021
Verlag: Springer Berlin Heidelberg
Erschienen in: Basic Research in Cardiology / Ausgabe 1/2021
Print ISSN: 0300-8428
Elektronische ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-021-00904-5

Neu im Fachgebiet Kardiologie

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

29.05.2024 Herzinfarkt Nachrichten

Bei Menschen mit Typ-2-Diabetes sind die Chancen, einen Myokardinfarkt zu überleben, in den letzten 15 Jahren deutlich gestiegen – nicht jedoch bei Betroffenen mit Typ 1.

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

28.05.2024 Nebenwirkungen der Krebstherapie Nachrichten

Kardiotoxische Nebenwirkungen einer Therapie mit Immuncheckpointhemmern mögen selten sein – wenn sie aber auftreten, wird es für Patienten oft lebensgefährlich. Voruntersuchung und Monitoring sind daher obligat.

GLP-1-Agonisten können Fortschreiten diabetischer Retinopathie begünstigen

24.05.2024 Diabetische Retinopathie Nachrichten

Möglicherweise hängt es von der Art der Diabetesmedikamente ab, wie hoch das Risiko der Betroffenen ist, dass sich sehkraftgefährdende Komplikationen verschlimmern.

TAVI versus Klappenchirurgie: Neue Vergleichsstudie sorgt für Erstaunen

21.05.2024 TAVI Nachrichten

Bei schwerer Aortenstenose und obstruktiver KHK empfehlen die Leitlinien derzeit eine chirurgische Kombi-Behandlung aus Klappenersatz plus Bypass-OP. Diese Empfehlung wird allerdings jetzt durch eine aktuelle Studie infrage gestellt – mit überraschender Deutlichkeit.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Single-cell transcriptomic identified HIF1A as a target for attenuating acute rejection after heart transplantation

Abstract

Neu im Fachgebiet Kardiologie

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

GLP-1-Agonisten können Fortschreiten diabetischer Retinopathie begünstigen

TAVI versus Klappenchirurgie: Neue Vergleichsstudie sorgt für Erstaunen

Update Kardiologie

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2021

Regulation of STAT3 and its role in cardioprotection by conditioning: focus on non-genomic roles targeting mitochondrial function

Ablation of lysozyme M-positive cells prevents aircraft noise-induced vascular damage without improving cerebral side effects

Plasminogen activator inhibitor-1 reduces cardiac fibrosis and promotes M2 macrophage polarization in inflammatory cardiomyopathy

Cardiomyocyte depolarization triggers NOS-dependent NO transient after calcium release, reducing the subsequent calcium transient

AAV-mediated expression of NFAT decoy oligonucleotides protects from cardiac hypertrophy and heart failure

Omecamtiv mecarbil evokes diastolic dysfunction and leads to periodic electromechanical alternans

Neu im Fachgebiet Kardiologie

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

GLP-1-Agonisten können Fortschreiten diabetischer Retinopathie begünstigen

TAVI versus Klappenchirurgie: Neue Vergleichsstudie sorgt für Erstaunen

Update Kardiologie