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Open Access 01-01-2016 | Report

Meeting report from the 2nd International Symposium on New Frontiers in Cardiovascular Research. Protecting the cardiovascular system from ischemia: between bench and bedside

Authors: Hector A. Cabrera-Fuentes, Corina Alba-Alba, Julian Aragones, Jürgen Bernhagen, William A. Boisvert, Hans E. Bøtker, Gabriela Cesarman-Maus, Ingrid Fleming, David Garcia-Dorado, Sandrine Lecour, Elisa Liehn, Michael S. Marber, Nephtali Marina, Manuel Mayr, Oscar Perez-Mendez, Tetsuji Miura, Marisol Ruiz-Meana, Eduardo M. Salinas-Estefanon, Sang-Bing Ong, Hans J. Schnittler, Jose T. Sanchez-Vega, Adriana Sumoza-Toledo, Carl-Wilhelm Vogel, Dina Yarullina, Derek M. Yellon, Klaus T. Preissner, Derek J. Hausenloy

Published in: Basic Research in Cardiology | Issue 1/2016

Abstract

Recent advances in basic cardiovascular research as well as their translation into the clinical situation were the focus at the last “New Frontiers in Cardiovascular Research meeting”. Major topics included the characterization of new targets and procedures in cardioprotection, deciphering new players and inflammatory mechanisms in ischemic heart disease as well as uncovering microRNAs and other biomarkers as versatile and possibly causal factors in cardiovascular pathogenesis. Although a number of pathological situations such as ischemia–reperfusion injury or atherosclerosis can be simulated and manipulated in diverse animal models, also to challenge new drugs for intervention, patient studies are the ultimate litmus test to obtain unequivocal information about the validity of biomedical concepts and their application in the clinics. Thus, the open and bidirectional exchange between bench and bedside is crucial to advance the field of ischemic heart disease with a particular emphasis of understanding long-lasting approaches in cardioprotection.

Abu Taha A, Schnittler HJ (2014) Dynamics between actin and the VE-cadherin/catenin complex: novel aspects of the ARP2/3 complex in regulation of endothelial junctions. Cell Adhes Migr 8:125–135CrossRef

Abu Taha A, Taha M, Seebach J, Schnittler HJ (2014) ARP2/3-mediated junction-associated lamellipodia control VE-cadherin-based cell junction dynamics and maintain monolayer integrity. Mol Biol Cell 25:245–256. doi:10.1091/mbc.E13-07-0404 PubMedCrossRef

Alampour-Rajabi S, El Bounkari O, Rot A, Muller-Newen G, Bachelerie F, Gawaz M, Weber C, Schober A, Bernhagen J (2015) MIF interacts with CXCR7 to promote receptor internalization, ERK1/2 and ZAP-70 signaling, and lymphocyte chemotaxis. FASEB J. doi:10.1096/fj.15-273904 PubMed

Alburquerque-Bejar JJ, Barba I, Inserte J, Miro-Casas E, Ruiz-Meana M, Poncelas M, Vilardosa U, Valls-Lacalle L, Rodriguez-Sinovas A, Garcia-Dorado D (2015) Combination therapy with remote ischaemic conditioning and insulin or exenatide enhances infarct size limitation in pigs. Cardiovasc Res 107:246–254. doi:10.1093/cvr/cvv171 PubMedCrossRef

Aragones J, Schneider M, Van Geyte K, Fraisl P, Dresselaers T, Mazzone M, Dirkx R, Zacchigna S, Lemieux H, Jeoung NH, Lambrechts D, Bishop T, Lafuste P, Diez-Juan A, Harten SK, Van Noten P, De Bock K, Willam C, Tjwa M, Grosfeld A, Navet R, Moons L, Vandendriessche T, Deroose C, Wijeyekoon B, Nuyts J, Jordan B, Silasi-Mansat R, Lupu F, Dewerchin M, Pugh C, Salmon P, Mortelmans L, Gallez B, Gorus F, Buyse J, Sluse F, Harris RA, Gnaiger E, Hespel P, Van Hecke P, Schuit F, Van Veldhoven P, Ratcliffe P, Baes M, Maxwell P, Carmeliet P (2008) Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism. Nat Genet 40:170–180. doi:10.1038/ng.2007.62 PubMedCrossRef

Baker JO, Tyther R, Liebetrau C, Clark J, Howarth R, Patterson T, Mollmann H, Nef H, Sicard P, Kailey B, Devaraj R, Redwood SR, Kunst G, Weber E, Marber MS (2015) Cardiac myosin-binding protein C: a potential early biomarker of myocardial injury. Basic Res Cardiol 110:23. doi:10.1007/s00395-015-0478-5 PubMedPubMedCentralCrossRef

Brulhart-Meynet MC, Braunersreuther V, Brinck J, Montecucco F, Prost JC, Thomas A, Galan K, Pelli G, Pedretti S, Vuilleumier N, Mach F, Lecour S, James RW, Frias MA (2015) Improving reconstituted HDL composition for efficient post-ischemic reduction of ischemia reperfusion injury. PLoS One 10:e0119664. doi:10.1371/journal.pone.0119664 PubMedPubMedCentralCrossRef

Cabrera-Fuentes HA, Lopez ML, McCurdy S, Fischer S, Meiler S, Baumer Y, Galuska SP, Preissner KT, Boisvert WA (2015) Regulation of monocyte/macrophage polarisation by extracellular RNA. Thromb Haemost 113:473–481. doi:10.1160/TH14-06-0507 PubMedPubMedCentralCrossRef

Cabrera-Fuentes HA, Niemann B, Grieshaber P, Wollbrueck M, Gehron J, Preissner KT, Boning A (2015) RNase1 as a potential mediator of remote ischaemic preconditioning for cardioprotectiondagger. Eur J Cardiothorac Surg. doi:10.1093/ejcts/ezu519 PubMed

10.

Cabrera-Fuentes HA, Preissner KT (2014) Abstract 20396: induction of ischemia-reperfusion injury by extracellular RNA: a case for tumor necrosis factor (TNF-α)—shedding. Circulation 130:A20396

11.

Cabrera-Fuentes HA, Ruiz-Meana M, Simsekyilmaz S, Kostin S, Inserte J, Saffarzadeh M, Galuska SP, Vijayan V, Barba I, Barreto G, Fischer S, Lochnit G, Ilinskaya ON, Baumgart-Vogt E, Boning A, Lecour S, Hausenloy DJ, Liehn EA, Garcia-Dorado D, Schluter KD, Preissner KT (2014) RNase1 prevents the damaging interplay between extracellular RNA and tumour necrosis factor-alpha in cardiac ischaemia/reperfusion injury. Thromb Haemost 112:1110–1119. doi:10.1160/TH14-08-0703 PubMedCrossRef

12.

Chatterjee M, Borst O, Walker B, Fotinos A, Vogel S, Seizer P, Mack A, Alampour-Rajabi S, Rath D, Geisler T, Lang F, Langer HF, Bernhagen J, Gawaz M (2014) Macrophage migration inhibitory factor limits activation-induced apoptosis of platelets via CXCR7-dependent Akt signaling. Circ Res 115:939–949. doi:10.1161/CIRCRESAHA.115.305171 PubMedCrossRef

13.

Cochain C, Zernecke A (2015) Macrophages and immune cells in atherosclerosis: recent advances and novel concepts. Basic Res Cardiol 110:34. doi:10.1007/s00395-015-0491-8 PubMedCrossRef

14.

Cung TT, Morel O, Cayla G, Rioufol G, Garcia-Dorado D, Angoulvant D, Bonnefoy-Cudraz E, Guerin P, Elbaz M, Delarche N, Coste P, Vanzetto G, Metge M, Aupetit JF, Jouve B, Motreff P, Tron C, Labeque JN, Steg PG, Cottin Y, Range G, Clerc J, Claeys MJ, Coussement P, Prunier F, Moulin F, Roth O, Belle L, Dubois P, Barragan P, Gilard M, Piot C, Colin P, De Poli F, Morice MC, Ider O, Dubois-Rande JL, Unterseeh T, Le Breton H, Beard T, Blanchard D, Grollier G, Malquarti V, Staat P, Sudre A, Elmer E, Hansson MJ, Bergerot C, Boussaha I, Jossan C, Derumeaux G, Mewton N, Ovize M (2015) Cyclosporine before PCI in patients with acute myocardial infarction. N Engl J Med 373:1021–1031. doi:10.1056/NEJMoa1505489 PubMedCrossRef

15.

Curaj A, Staudt M, Fatu R, Kraaijeveld AO, Jankowski J, Biessen EAL, Liehn EA (2015) Blockade of CCR3 retains the neutrophils, preserving their survival during healing after myocardial infarction. Discoveries 3:e45. doi:10.15190/d.2015.37 CrossRef

16.

de Brito OM, Scorrano L (2008) Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature 456:605–610. doi:10.1038/nature07534 PubMedCrossRef

17.

de Brito OM, Scorrano L (2008) Mitofusin 2: a mitochondria-shaping protein with signaling roles beyond fusion. Antioxid Redox Signal 10:621–633. doi:10.1089/ars.2007.1934 PubMedCrossRef

18.

Elgheznawy A, Shi L, Hu J, Wittig I, Laban H, Pircher J, Mann A, Provost P, Randriamboavonjy V, Fleming I (2015) Dicer cleavage by calpain determines platelet microRNA levels and function in diabetes. Circ Res 117:157–165. doi:10.1161/CIRCRESAHA.117.305784 PubMedCrossRef

19.

Elorza A, Soro-Arnaiz I, Melendez-Rodriguez F, Rodriguez-Vaello V, Marsboom G, de Carcer G, Acosta-Iborra B, Albacete-Albacete L, Ordonez A, Serrano-Oviedo L, Gimenez-Bachs JM, Vara-Vega A, Salinas A, Sanchez-Prieto R, Martin del Rio R, Sanchez-Madrid F, Malumbres M, Landazuri MO, Aragones J (2012) HIF2alpha acts as an mTORC1 activator through the amino acid carrier SLC7A5. Mol Cell 48:681–691. doi:10.1016/j.molcel.2012.09.017 PubMedCrossRef

20.

Ferdinandy P, Hausenloy DJ, Heusch G, Baxter GF, Schulz R (2014) Interaction of risk factors, comorbidities, and comedications with ischemia/reperfusion injury and cardioprotection by preconditioning, postconditioning, and remote conditioning. Pharmacol Rev 66:1142–1174. doi:10.1124/pr.113.008300 PubMedCrossRef

21.

Fernandez-Sanz C, Ruiz-Meana M, Castellano J, Miro-Casas E, Nunez E, Inserte J, Vazquez J, Garcia-Dorado D (2015) Altered FoF1 ATP synthase and susceptibility to mitochondrial permeability transition pore during ischaemia and reperfusion in aging cardiomyocytes. Thromb Haemost 113:441–451. doi:10.1160/TH14-10-0901 PubMedCrossRef

22.

Fernandez-Sanz C, Ruiz-Meana M, Miro-Casas E, Nunez E, Castellano J, Loureiro M, Barba I, Poncelas M, Rodriguez-Sinovas A, Vazquez J, Garcia-Dorado D (2014) Defective sarcoplasmic reticulum-mitochondria calcium exchange in aged mouse myocardium. Cell Death Dis 5:e1573. doi:10.1038/cddis.2014.526 PubMedPubMedCentralCrossRef

23.

Fraccaroli A, Pitter B, Taha AA, Seebach J, Huveneers S, Kirsch J, Casaroli-Marano RP, Zahler S, Pohl U, Gerhardt H, Schnittler HJ, Montanez E (2015) Endothelial alpha-parvin controls integrity of developing vasculature and is required for maintenance of cell-cell junctions. Circ Res 117:29–40. doi:10.1161/CIRCRESAHA.117.305818 PubMedPubMedCentralCrossRef

24.

Garcia-Sanchez C, Posadas-Romero C, Posadas-Sanchez R, Carreon-Torres E, Rodriguez-Perez JM, Juarez-Rojas JG, Martinez-Sanchez C, Fragoso JM, Gonzalez-Pacheco H, Vargas-Alarcon G, Perez-Mendez O (2015) Low concentrations of phospholipids and plasma HDL cholesterol subclasses in asymptomatic subjects with high coronary calcium scores. Atherosclerosis 238:250–255. doi:10.1016/j.atherosclerosis.2014.12.004 PubMedCrossRef

25.

Giannitsis E, Katus HA (2015) A long way to translation: will cMyC survive? Basic Res Cardiol 110:479. doi:10.1007/s00395-015-0479-4

26.

Hall AR, Burke N, Dongworth RK, Hausenloy DJ (2014) Mitochondrial fusion and fission proteins: novel therapeutic targets for combating cardiovascular disease. Br J Pharmacol 171:1890–1906. doi:10.1111/bph.12516 PubMedPubMedCentralCrossRef

27.

Hausenloy DJ, Baxter G, Bell R, Botker HE, Davidson SM, Downey J, Heusch G, Kitakaze M, Lecour S, Mentzer R, Mocanu MM, Ovize M, Schulz R, Shannon R, Walker M, Walkinshaw G, Yellon DM (2010) Translating novel strategies for cardioprotection: the hatter workshop recommendations. Basic Res Cardiol 105:677–686. doi:10.1007/s00395-010-0121-4 PubMedPubMedCentralCrossRef

28.

Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, Knight R, Kunst G, Laing C, Nicholas J, Pepper J, Robertson S, Xenou M, Clayton T, Yellon DM, Investigators ET (2015) Remote ischemic preconditioning and outcomes of cardiac surgery. N Engl J Med 373:1408–1417. doi:10.1056/NEJMoa1413534 PubMedCrossRef

29.

Hausenloy DJ, Erik Botker H, Condorelli G, Ferdinandy P, Garcia-Dorado D, Heusch G, Lecour S, van Laake LW, Madonna R, Ruiz-Meana M, Schulz R, Sluijter JP, Yellon DM, Ovize M (2013) Translating cardioprotection for patient benefit: position paper from the Working Group of Cellular Biology of the Heart of the European Society of Cardiology. Cardiovasc Res 98:7–27. doi:10.1093/cvr/cvt004 PubMedCrossRef

30.

Hausenloy DJ, Yellon DM (2008) GLP-1 therapy: beyond glucose control. Circ Heart Fail 1:147–149. doi:10.1161/CIRCHEARTFAILURE.108.810887 PubMedCrossRef

31.

Hausenloy DJ, Yellon DM (2008) Remote ischaemic preconditioning: underlying mechanisms and clinical application. Cardiovasc Res 79:377–386. doi:10.1093/cvr/cvn114 PubMedCrossRef

32.

Hausenloy DJ, Yellon DM (2015) Targeting myocardial reperfusion injury—the search continues. N Engl J Med 373:1073–1075. doi:10.1056/NEJMe1509718 PubMedCrossRef

33.

Heusch G (2013) Cardioprotection: chances and challenges of its translation to the clinic. Lancet 381:166–175. doi:10.1016/S0140-6736(12)60916-7 PubMedCrossRef

34.

Heusch G (2015) CIRCUS: a kiss of death for cardioprotection? Cardiovasc Res 108:215–216. doi:10.1093/cvr/cvv225 PubMedCrossRef

35.

Heusch G (2012) HIF-1alpha and paradoxical phenomena in cardioprotection. Cardiovasc Res 96:214–215. doi:10.1093/cvr/cvs145 (discussion 216-219) PubMedCrossRef

36.

Heusch G (2015) Molecular basis of cardioprotection: signal transduction in ischemic pre-, post-, and remote conditioning. Circ Res 116:674–699. doi:10.1161/CIRCRESAHA.116.305348 PubMedCrossRef

37.

Heusch G, Botker HE, Przyklenk K, Redington A, Yellon D (2015) Remote ischemic conditioning. J Am Coll Cardiol 65:177–195. doi:10.1016/j.jacc.2014.10.031 PubMedCrossRef

38.

Heusch G, Gersh BJ (2015) ERICCA and RIPHeart: two nails in the coffin for cardioprotection by remote ischemic conditioning? Probably not! Eur Heart J. doi:10.1093/eurheartj/ehv606

39.

Hoffman NE, Miller BA, Wang J, Elrod JW, Rajan S, Gao E, Song J, Zhang XQ, Hirschler-Laszkiewicz I, Shanmughapriya S, Koch WJ, Feldman AM, Madesh M, Cheung JY (2015) Ca(2)(+) entry via Trpm2 is essential for cardiac myocyte bioenergetics maintenance. Am J Physiol Heart Circ Physiol 308:H637–H650. doi:10.1152/ajpheart.00720.2014 PubMedCrossRef

40.

Ibanez B, Heusch G, Ovize M, Van de Werf F (2015) Evolving therapies for myocardial ischemia/reperfusion injury. J Am Coll Cardiol 65:1454–1471. doi:10.1016/j.jacc.2015.02.032 PubMedCrossRef

41.

Jacquet S, Yin X, Sicard P, Clark J, Kanaganayagam GS, Mayr M, Marber MS (2009) Identification of cardiac myosin-binding protein C as a candidate biomarker of myocardial infarction by proteomics analysis. Mol Cell Proteomics 8:2687–2699. doi:10.1074/mcp.M900176-MCP200 PubMedPubMedCentralCrossRef

42.

Javadov SA, Lim KH, Kerr PM, Suleiman MS, Angelini GD, Halestrap AP (2000) Protection of hearts from reperfusion injury by propofol is associated with inhibition of the mitochondrial permeability transition. Cardiovasc Res 45:360–369PubMedCrossRef

43.

Kanzler I, Tuchscheerer N, Steffens G, Simsekyilmaz S, Konschalla S, Kroh A, Simons D, Asare Y, Schober A, Bucala R, Weber C, Bernhagen J, Liehn EA (2013) Differential roles of angiogenic chemokines in endothelial progenitor cell-induced angiogenesis. Basic Res Cardiol 108:310. doi:10.1007/s00395-012-0310-4 PubMedPubMedCentralCrossRef

44.

Karlsson LO, Zhou AX, Larsson E, Astrom-Olsson K, Mansson C, Akyurek LM, Grip L (2010) Cyclosporine does not reduce myocardial infarct size in a porcine ischemia-reperfusion model. J Cardiovasc Pharmacol Ther 15:182–189. doi:10.1177/1074248410362074 PubMedCrossRef

45.

Kitamoto S, Egashira K, Ichiki T, Han X, McCurdy S, Sakuda S, Sunagawa K, Boisvert WA (2013) Chitinase inhibition promotes atherosclerosis in hyperlipidemic mice. Am J Pathol 183:313–325. doi:10.1016/j.ajpath.2013.04.003 PubMedPubMedCentralCrossRef

46.

Kojima I, Tanaka T, Inagi R, Kato H, Yamashita T, Sakiyama A, Ohneda O, Takeda N, Sata M, Miyata T, Fujita T, Nangaku M (2007) Protective role of hypoxia-inducible factor-2alpha against ischemic damage and oxidative stress in the kidney. J Am Soc Nephrol 18:1218–1226. doi:10.1681/ASN.2006060639 PubMedCrossRef

47.

Korley FK, Jaffe AS (2013) Preparing the United States for high-sensitivity cardiac troponin assays. J Am Coll Cardiol 61:1753–1758. doi:10.1016/j.jacc.2012.09.069 PubMedCrossRef

48.

Kottenberg E, Musiolik J, Thielmann M, Jakob H, Peters J, Heusch G (2014) Interference of propofol with signal transducer and activator of transcription 5 activation and cardioprotection by remote ischemic preconditioning during coronary artery bypass grafting. J Thorac Cardiovasc Surg 147:376–382. doi:10.1016/j.jtcvs.2013.01.005 PubMedCrossRef

49.

Kottenberg E, Thielmann M, Bergmann L, Heine T, Jakob H, Heusch G, Peters J (2012) Protection by remote ischemic preconditioning during coronary artery bypass graft surgery with isoflurane but not propofol—a clinical trial. Acta Anaesthesiol Scand 56:30–38. doi:10.1111/j.1399-6576.2011.02585.x PubMedCrossRef

50.

Kzhyshkowska J, Gratchev A, Goerdt S (2007) Human chitinases and chitinase-like proteins as indicators for inflammation and cancer. Biomark Insights 2:128–146PubMedPubMedCentral

51.

Lange I, Yamamoto S, Partida-Sanchez S, Mori Y, Fleig A, Penner R (2009) TRPM2 functions as a lysosomal Ca2+-release channel in beta cells. Sci Signal 2:ra23. doi:10.1126/scisignal.2000278 PubMedPubMedCentralCrossRef

52.

Lecour S, Botker HE, Condorelli G, Davidson SM, Garcia-Dorado D, Engel FB, Ferdinandy P, Heusch G, Madonna R, Ovize M, Ruiz-Meana M, Schulz R, Sluijter JP, Van Laake LW, Yellon DM, Hausenloy DJ (2014) ESC working group cellular biology of the heart: position paper: improving the preclinical assessment of novel cardioprotective therapies. Cardiovasc Res 104:399–411. doi:10.1093/cvr/cvu225 PubMedPubMedCentralCrossRef

53.

Li J, Iorga A, Sharma S, Youn JY, Partow-Navid R, Umar S, Cai H, Rahman S, Eghbali M (2012) Intralipid, a clinically safe compound, protects the heart against ischemia-reperfusion injury more efficiently than cyclosporine-A. Anesthesiology 117:836–846. doi:10.1097/ALN.0b013e3182655e73 PubMedPubMedCentralCrossRef

54.

Li W, Zhang Y, Liu Y, Yue F, Lu Y, Qiu H, Gao D, Gao Y, Wu Y, Wang Z, Huang R, Zhang C (2012) In vitro kinetic evaluation of the free radical scavenging ability of propofol. Anesthesiology 116:1258–1266. doi:10.1097/ALN.0b013e3182567dcc PubMedCrossRef

55.

Liehn EA, Cabrera-Fuentes HA (2015) Inflammation between defense and disease: impact on tissue repair and chronic sickness. Discoveries 3(1):e42. doi:10.15190/d.2015.34 CrossRef

56.

Liehn EA, Piccinini AM, Koenen RR, Soehnlein O, Adage T, Fatu R, Curaj A, Popescu A, Zernecke A, Kungl AJ, Weber C (2010) A new monocyte chemotactic protein-1/chemokine CC motif ligand-2 competitor limiting neointima formation and myocardial ischemia/reperfusion injury in mice. J Am Coll Cardiol 56:1847–1857. doi:10.1016/j.jacc.2010.04.066 PubMedCrossRef

57.

Liehn EA, Postea O, Curaj A, Marx N (2011) Repair after myocardial infarction, between fantasy and reality: the role of chemokines. J Am Coll Cardiol 58:2357–2362. doi:10.1016/j.jacc.2011.08.034 PubMedCrossRef

58.

Liehn EA, Tuchscheerer N, Kanzler I, Drechsler M, Fraemohs L, Schuh A, Koenen RR, Zander S, Soehnlein O, Hristov M, Grigorescu G, Urs AO, Leabu M, Bucur I, Merx MW, Zernecke A, Ehling J, Gremse F, Lammers T, Kiessling F, Bernhagen J, Schober A, Weber C (2011) Double-edged role of the CXCL12/CXCR4 axis in experimental myocardial infarction. J Am Coll Cardiol 58:2415–2423. doi:10.1016/j.jacc.2011.08.033 PubMedCrossRef

59.

Lim KH, Halestrap AP, Angelini GD, Suleiman MS (2005) Propofol is cardioprotective in a clinically relevant model of normothermic blood cardioplegic arrest and cardiopulmonary bypass. Exp Biol Med (Maywood) 230:413–420

60.

Lim WY, Messow CM, Berry C (2012) Cyclosporin variably and inconsistently reduces infarct size in experimental models of reperfused myocardial infarction: a systematic review and meta-analysis. Br J Pharmacol 165:2034–2043. doi:10.1111/j.1476-5381.2011.01691.x PubMedPubMedCentralCrossRef

61.

Lonborg J, Vejlstrup N, Kelbaek H, Botker HE, Kim WY, Mathiasen AB, Jorgensen E, Helqvist S, Saunamaki K, Clemmensen P, Holmvang L, Thuesen L, Krusell LR, Jensen JS, Kober L, Treiman M, Holst JJ, Engstrom T (2012) Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. Eur Heart J 33:1491–1499. doi:10.1093/eurheartj/ehr309 PubMedCrossRef

62.

Lopez ML, Bruges G, Crespo G, Salazar V, Deglesne PA, Schneider H, Cabrera-Fuentes H, Schmitz ML, Preissner KT (2014) Thrombin selectively induces transcription of genes in human monocytes involved in inflammation and wound healing. Thromb Haemost 112:992–1001. doi:10.1160/TH14-01-0034 PubMedCrossRef

63.

Luna-Luna M, Medina-Urrutia A, Vargas-Alarcon G, Coss-Rovirosa F, Vargas-Barron J, Perez-Mendez O (2015) Adipose tissue in metabolic syndrome: onset and progression of atherosclerosis. Arch Med Res 46:392–407. doi:10.1016/j.arcmed.2015.05.007 PubMedCrossRef

64.

Marina N, Ang R, Machhada A, Kasymov V, Karagiannis A, Hosford PS, Mosienko V, Teschemacher AG, Vihko P, Paton JF, Kasparov S, Gourine AV (2015) Brainstem hypoxia contributes to the development of hypertension in the spontaneously hypertensive rat. Hypertension 65:775–783. doi:10.1161/HYPERTENSIONAHA.114.04683 PubMedPubMedCentralCrossRef

65.

Marina N, Tang F, Figueiredo M, Mastitskaya S, Kasimov V, Mohamed-Ali V, Roloff E, Teschemacher AG, Gourine AV, Kasparov S (2013) Purinergic signalling in the rostral ventro-lateral medulla controls sympathetic drive and contributes to the progression of heart failure following myocardial infarction in rats. Basic Res Cardiol 108:317. doi:10.1007/s00395-012-0317-x PubMedPubMedCentralCrossRef

66.

Mayr M, Zampetaki A, Willeit P, Willeit J, Kiechl S (2013) MicroRNAs within the continuum of postgenomics biomarker discovery. Arterioscler Thromb Vasc Biol 33:206–214. doi:10.1161/ATVBAHA.112.300141 PubMedCrossRef

67.

Meybohm P, Bein B, Brosteanu O, Cremer J, Gruenewald M, Stoppe C, Coburn M, Schaelte G, Boning A, Niemann B, Roesner J, Kletzin F, Strouhal U, Reyher C, Laufenberg-Feldmann R, Ferner M, Brandes IF, Bauer M, Stehr SN, Kortgen A, Wittmann M, Baumgarten G, Meyer-Treschan T, Kienbaum P, Heringlake M, Schon J, Sander M, Treskatsch S, Smul T, Wolwender E, Schilling T, Fuernau G, Hasenclever D, Zacharowski K, Collaborators RIS (2015) A multicenter trial of remote ischemic preconditioning for heart surgery. N Engl J Med 373:1397–1407. doi:10.1056/NEJMoa1413579 PubMedCrossRef

68.

Miller BA, Hoffman NE, Merali S, Zhang XQ, Wang J, Rajan S, Shanmughapriya S, Gao E, Barrero CA, Mallilankaraman K, Song J, Gu T, Hirschler-Laszkiewicz I, Koch WJ, Feldman AM, Madesh M, Cheung JY (2014) TRPM2 channels protect against cardiac ischemia-reperfusion injury: role of mitochondria. J Biol Chem 289:7615–7629. doi:10.1074/jbc.M113.533851 PubMedPubMedCentralCrossRef

69.

Moss JW, Ramji DP (2015) Interferon-gamma: promising therapeutic target in atherosclerosis. World J Exp Med 5:154–159. doi:10.5493/wjem.v5.i3.154 PubMedPubMedCentralCrossRef

70.

Mueller C (2014) Biomarkers and acute coronary syndromes: an update. Eur Heart J 35:552–556. doi:10.1093/eurheartj/eht530 PubMedCrossRef

71.

Munk K, Andersen NH, Schmidt MR, Nielsen SS, Terkelsen CJ, Sloth E, Botker HE, Nielsen TT, Poulsen SH (2010) Remote ischemic conditioning in patients with myocardial infarction treated with primary angioplasty: impact on left ventricular function assessed by comprehensive echocardiography and gated single-photon emission CT. Circ Cardiovasc Imaging 3:656–662. doi:10.1161/CIRCIMAGING.110.957340 PubMedCrossRef

72.

Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124–1136PubMedCrossRef

73.

Oda S, Uchida K, Wang X, Lee J, Shimada Y, Tominaga M, Kadowaki M (2013) TRPM2 contributes to antigen-stimulated Ca(2)(+) influx in mucosal mast cells. Pflugers Arch 465:1023–1030. doi:10.1007/s00424-013-1219-y PubMedCrossRef

74.

Ong SB, Dongworth RK, Cabrera-Fuentes HA, Hausenloy DJ (2015) Role of the MPTP in conditioning the heart—translatability and mechanism. Br J Pharmacol 172:2074–2084. doi:10.1111/bph.13013 PubMedPubMedCentralCrossRef

75.

Ong SB, Kalkhoran SB, Cabrera-Fuentes HA, Hausenloy DJ (2015) Mitochondrial fusion and fission proteins as novel therapeutic targets for treating cardiovascular disease. Eur J Pharmacol 763:104–114. doi:10.1016/j.ejphar.2015.04.056 PubMedCrossRef

76.

Ong SB, Subrayan S, Lim SY, Yellon DM, Davidson SM, Hausenloy DJ (2010) Inhibiting mitochondrial fission protects the heart against ischemia/reperfusion injury. Circulation 121:2012–2022. doi:10.1161/CIRCULATIONAHA.109.906610 PubMedCrossRef

77.

Ong SG, Lee WH, Theodorou L, Kodo K, Lim SY, Shukla DH, Briston T, Kiriakidis S, Ashcroft M, Davidson SM, Maxwell PH, Yellon DM, Hausenloy DJ (2014) HIF-1 reduces ischaemia-reperfusion injury in the heart by targeting the mitochondrial permeability transition pore. Cardiovasc Res 104:24–36. doi:10.1093/cvr/cvu172 PubMedCrossRef

78.

Pickard JM, Botker HE, Crimi G, Davidson B, Davidson SM, Dutka D, Ferdinandy P, Ganske R, Garcia-Dorado D, Giricz Z, Gourine AV, Heusch G, Kharbanda R, Kleinbongard P, MacAllister R, McIntyre C, Meybohm P, Prunier F, Redington A, Robertson NJ, Suleiman MS, Vanezis A, Walsh S, Yellon DM, Hausenloy DJ (2015) Remote ischemic conditioning: from experimental observation to clinical application: report from the 8th Biennial Hatter Cardiovascular Institute Workshop. Basic Res Cardiol 110:453. doi:10.1007/s00395-014-0453-6 PubMedPubMedCentralCrossRef

79.

Piot C, Croisille P, Staat P, Thibault H, Rioufol G, Mewton N, Elbelghiti R, Cung TT, Bonnefoy E, Angoulvant D, Macia C, Raczka F, Sportouch C, Gahide G, Finet G, Andre-Fouet X, Revel D, Kirkorian G, Monassier JP, Derumeaux G, Ovize M (2008) Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N Engl J Med 359:473–481. doi:10.1056/NEJMoa071142 PubMedCrossRef

80.

Preissner KT, Boisvert WA, Hausenloy DJ (2015) Surfing on the cardiovascular frontier wave. Thromb Haemost 113:439–440. doi:10.1160/TH15-01-0086 PubMedCrossRef

81.

Ralph GS, Parham S, Lee SR, Beard GL, Craigon MH, Ward N, White JR, Barber RD, Rayner W, Kingsman SM, Mundy CR, Mazarakis ND, Krige D (2004) Identification of potential stroke targets by lentiviral vector mediated overexpression of HIF-1 alpha and HIF-2 alpha in a primary neuronal model of hypoxia. J Cereb Blood Flow Metab 24:245–258. doi:10.1097/01.WCB.0000110532.48786.46 PubMedCrossRef

82.

Randriamboavonjy V, Isaak J, Elgheznawy A, Pistrosch F, Fromel T, Yin X, Badenhoop K, Heide H, Mayr M, Fleming I (2012) Calpain inhibition stabilizes the platelet proteome and reactivity in diabetes. Blood 120:415–423. doi:10.1182/blood-2011-12-399980 PubMedCrossRef

83.

Rodriguez-Sinovas A, Cabestrero A, Garcia del Blanco B, Inserte J, Garcia A, Garcia-Dorado D (2009) Intracoronary acid infusion as an alternative to ischemic postconditioning in pigs. Basic Res Cardiol 104:761–771. doi:10.1007/s00395-009-0032-4 PubMedCrossRef

84.

Sattler K, Graler M, Keul P, Weske S, Reimann CM, Jindrova H, Kleinbongard P, Sabbadini R, Brocker-Preuss M, Erbel R, Heusch G, Levkau B (2015) Defects of high-density lipoproteins in coronary artery disease caused by low sphingosine-1-phosphate content: correction by sphingosine-1-phosphate-loading. J Am Coll Cardiol 66:1470–1485. doi:10.1016/j.jacc.2015.07.057 PubMedCrossRef

85.

Sattler KJ, Elbasan S, Keul P, Elter-Schulz M, Bode C, Graler MH, Brocker-Preuss M, Budde T, Erbel R, Heusch G, Levkau B (2010) Sphingosine 1-phosphate levels in plasma and HDL are altered in coronary artery disease. Basic Res Cardiol 105:821–832. doi:10.1007/s00395-010-0112-5 PubMedCrossRef

86.

Sattler KJ, Herrmann J, Yun S, Lehmann N, Wang Z, Heusch G, Sack S, Erbel R, Levkau B (2009) High high-density lipoprotein-cholesterol reduces risk and extent of percutaneous coronary intervention-related myocardial infarction and improves long-term outcome in patients undergoing elective percutaneous coronary intervention. Eur Heart J 30:1894–1902. doi:10.1093/eurheartj/ehp183 PubMedCrossRef

87.

Sayin MM, Ozatamer O, Tasoz R, Kilinc K, Unal N (2002) Propofol attenuates myocardial lipid peroxidation during coronary artery bypass grafting surgery. Br J Anaesth 89:242–246PubMedCrossRef

88.

Schnittler H, Taha M, Schnittler MO, Taha AA, Lindemann N, Seebach J (2014) Actin filament dynamics and endothelial cell junctions: the Ying and Yang between stabilization and motion. Cell Tissue Res 355:529–543. doi:10.1007/s00441-014-1856-2 PubMedCrossRef

89.

Schuh A, Butzbach B, Curaj A, Simsekyilmaz S, Bucur O, Kanzler I, Denecke B, Konschalla S, Kroh A, Sönmez TT, Marx N, Liehn EA (2014) Novel insights into the mechanism of cell-based therapy after chronic myocardial infarction. Discoveries 1:e9

90.

Seebach J, Taha AA, Lenk J, Lindemann N, Jiang X, Brinkmann K, Bogdan S, Schnittler HJ (2015) The cell border tracker, a novel tool to quantitatively analyze spatiotemporal endothelial junction dynamics at the subcellular level. Histochem Cell Biol. doi:10.1007/s00418-015-1357-8 PubMed

91.

Simsekyilmaz S, Cabrera-Fuentes HA, Meiler S, Kostin S, Baumer Y, Liehn EA, Weber C, Boisvert WA, Preissner KT, Zernecke A (2014) Response to letter regarding article “role of extracellular RNA in atherosclerotic plaque formation in mice”. Circulation 130:e144–e145. doi:10.1161/CIRCULATIONAHA.114.012346 PubMedCrossRef

92.

Simsekyilmaz S, Cabrera-Fuentes HA, Meiler S, Kostin S, Baumer Y, Liehn EA, Weber C, Boisvert WA, Preissner KT, Zernecke A (2014) Role of extracellular RNA in atherosclerotic plaque formation in mice. Circulation 129:598–606. doi:10.1161/CIRCULATIONAHA.113.002562 PubMedPubMedCentralCrossRef

93.

Sivaraman V, Pickard JM, Hausenloy DJ (2015) Remote ischaemic conditioning: cardiac protection from afar. Anaesthesia 70:732–748. doi:10.1111/anae.12973 PubMedCrossRef

94.

Sloth AD, Schmidt MR, Munk K, Kharbanda RK, Redington AN, Schmidt M, Pedersen L, Sorensen HT, Botker HE, Investigators C (2014) Improved long-term clinical outcomes in patients with ST-elevation myocardial infarction undergoing remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention. Eur Heart J 35:168–175. doi:10.1093/eurheartj/eht369 PubMedCrossRef

95.

Stegemann C, Pechlaner R, Willeit P, Langley SR, Mangino M, Mayr U, Menni C, Moayyeri A, Santer P, Rungger G, Spector TD, Willeit J, Kiechl S, Mayr M (2014) Lipidomics profiling and risk of cardiovascular disease in the prospective population-based Bruneck study. Circulation 129:1821–1831. doi:10.1161/CIRCULATIONAHA.113.002500 PubMedCrossRef

96.

Stoppe C, Rex S, Goetzenich A, Kraemer S, Emontzpohl C, Soppert J, Averdunk L, Sun Y, Rossaint R, Lue H, Huang C, Song Y, Pantouris G, Lolis E, Leng L, Schulte W, Bucala R, Weber C, Bernhagen J (2015) Interaction of MIF family proteins in myocardial ischemia/reperfusion damage and their influence on clinical outcome of cardiac surgery patients. Antioxid Redox Signal. doi:10.1089/ars.2014.6243 PubMedPubMedCentral

97.

Sumoza-Toledo A, Lange I, Cortado H, Bhagat H, Mori Y, Fleig A, Penner R, Partida-Sanchez S (2011) Dendritic cell maturation and chemotaxis is regulated by TRPM2-mediated lysosomal Ca2+ release. FASEB J 25:3529–3542. doi:10.1096/fj.10-178483 PubMedPubMedCentralCrossRef

98.

Sumoza-Toledo A, Penner R (2011) TRPM2: a multifunctional ion channel for calcium signalling. J Physiol 589:1515–1525. doi:10.1113/jphysiol.2010.201855 PubMedPubMedCentralCrossRef

99.

Sunaga D, Tanno M, Kuno A, Ishikawa S, Ogasawara M, Yano T, Miki T, Miura T (2014) Accelerated recovery of mitochondrial membrane potential by GSK-3beta inactivation affords cardiomyocytes protection from oxidant-induced necrosis. PLoS One 9:e112529. doi:10.1371/journal.pone.0112529 PubMedPubMedCentralCrossRef

100.

Tanno M, Kuno A, Ishikawa S, Miki T, Kouzu H, Yano T, Murase H, Tobisawa T, Ogasawara M, Horio Y, Miura T (2014) Translocation of glycogen synthase kinase-3beta (GSK-3beta), a trigger of permeability transition, is kinase activity-dependent and mediated by interaction with voltage-dependent anion channel 2 (VDAC2). J Biol Chem 289:29285–29296. doi:10.1074/jbc.M114.563924 PubMedPubMedCentralCrossRef

101.

Thielmann M, Kottenberg E, Kleinbongard P, Wendt D, Gedik N, Pasa S, Price V, Tsagakis K, Neuhauser M, Peters J, Jakob H, Heusch G (2013) Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial. Lancet 382:597–604. doi:10.1016/S0140-6736(13)61450-6 PubMedCrossRef

102.

Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, Joint ESCAAHAWHFTFftUDoMI, Katus HA, Lindahl B, Morrow DA, Clemmensen PM, Johanson P, Hod H, Underwood R, Bax JJ, Bonow RO, Pinto F, Gibbons RJ, Fox KA, Atar D, Newby LK, Galvani M, Hamm CW, Uretsky BF, Steg PG, Wijns W, Bassand JP, Menasche P, Ravkilde J, Ohman EM, Antman EM, Wallentin LC, Armstrong PW, Simoons ML, Januzzi JL, Nieminen MS, Gheorghiade M, Filippatos G, Luepker RV, Fortmann SP, Rosamond WD, Levy D, Wood D, Smith SC, Hu D, Lopez-Sendon JL, Robertson RM, Weaver D, Tendera M, Bove AA, Parkhomenko AN, Vasilieva EJ, Mendis S (2012) Third universal definition of myocardial infarction. Circulation 126:2020–2035. doi:10.1161/CIR.0b013e31826e1058

103.

Timmers L, Henriques JP, de Kleijn DP, Devries JH, Kemperman H, Steendijk P, Verlaan CW, Kerver M, Piek JJ, Doevendans PA, Pasterkamp G, Hoefer IE (2009) Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury. J Am Coll Cardiol 53:501–510. doi:10.1016/j.jacc.2008.10.033 PubMedCrossRef

104.

WHO (2015) Cardiovascular diseases (CVDs). Fact Sheet 317. In: World Health Organisation. Available from: URL: http://www.who.int/mediacentre/factsheets/fs317/en/

105.

Willeit P, Kiechl S, Kronenberg F, Witztum JL, Santer P, Mayr M, Xu Q, Mayr A, Willeit J, Tsimikas S (2014) Discrimination and net reclassification of cardiovascular risk with lipoprotein(a): prospective 15-year outcomes in the Bruneck Study. J Am Coll Cardiol 64:851–860. doi:10.1016/j.jacc.2014.03.061 PubMedCrossRef

106.

Willeit P, Zampetaki A, Dudek K, Kaudewitz D, King A, Kirkby NS, Crosby-Nwaobi R, Prokopi M, Drozdov I, Langley SR, Sivaprasad S, Markus HS, Mitchell JA, Warner TD, Kiechl S, Mayr M (2013) Circulating microRNAs as novel biomarkers for platelet activation. Circ Res 112:595–600. doi:10.1161/CIRCRESAHA.111.300539 PubMedCrossRef

107.

Yellon DM, Ackbarkhan AK, Balgobin V, Bulluck H, Deelchand A, Dhuny MR, Domah N, Gaoneadry D, Jagessur RK, Joonas N, Kowlessur S, Lutchoo J, Nicholas JM, Pauvaday K, Shamloll O, Walker JM, Hausenloy DJ (2015) Remote ischemic conditioning reduces myocardial infarct size in STEMI patients treated by thrombolysis. J Am Coll Cardiol 65:2764–2765. doi:10.1016/j.jacc.2015.02.082 PubMedCrossRef

108.

Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, Prokopi M, Mayr A, Weger S, Oberhollenzer F, Bonora E, Shah A, Willeit J, Mayr M (2010) Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res 107:810–817. doi:10.1161/CIRCRESAHA.110.226357 PubMedCrossRef

109.

Zampetaki A, Mayr M (2015) Sweet dicer: impairment of micro-RNA processing by diabetes. Circ Res 117:116–118. doi:10.1161/CIRCRESAHA.117.306817 PubMedCrossRef

110.

Zampetaki A, Willeit P, Tilling L, Drozdov I, Prokopi M, Renard JM, Mayr A, Weger S, Schett G, Shah A, Boulanger CM, Willeit J, Chowienczyk PJ, Kiechl S, Mayr M (2012) Prospective study on circulating MicroRNAs and risk of myocardial infarction. J Am Coll Cardiol 60:290–299. doi:10.1016/j.jacc.2012.03.056 PubMedCrossRef

Title: Meeting report from the 2nd International Symposium on New Frontiers in Cardiovascular Research. Protecting the cardiovascular system from ischemia: between bench and bedside
Authors: Hector A. Cabrera-Fuentes
Corina Alba-Alba
Julian Aragones
Jürgen Bernhagen
William A. Boisvert
Hans E. Bøtker
Gabriela Cesarman-Maus
Ingrid Fleming
David Garcia-Dorado
Sandrine Lecour
Elisa Liehn
Michael S. Marber
Nephtali Marina
Manuel Mayr
Oscar Perez-Mendez
Tetsuji Miura
Marisol Ruiz-Meana
Eduardo M. Salinas-Estefanon
Sang-Bing Ong
Hans J. Schnittler
Jose T. Sanchez-Vega
Adriana Sumoza-Toledo
Carl-Wilhelm Vogel
Dina Yarullina
Derek M. Yellon
Klaus T. Preissner
Derek J. Hausenloy
Publication date: 01-01-2016
Publisher: Springer Berlin Heidelberg
Published in: Basic Research in Cardiology / Issue 1/2016
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-015-0527-0

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