Donald M.Lyall, Carlos A.Celis-Morales, JanaAnderson, Jason M. R.Gill, Daniel F.Mackay, Andrew M.McIntosh, Daniel J.Smith, Ian J.Deary, NaveedSattar, Jill P.PellEur Heart J(2016)ehw528DOI: http://dx.doi.org/10.1093/eurheartj/ehw528First published online: 15 November 2016 (7 pages)
Azmil H.Abdul-Rahim, Ana-CristinaPerez, Rachael L.MacIsaac, Pardeep S.Jhund, Brian L.Claggett, Peter E.Carson, MichelKomajda, Robert S.McKelvie, Michael R.Zile, KarlSwedberg, SalimYusuf, Marc A.Pfeffer, Scott D.Solomon, Gregory Y.H.Lip, Kennedy R.Lees, John J.V.McMurrayEur Heart J(2016)ehw509DOI: http://dx.doi.org/10.1093/eurheartj/ehw509First published online: 13 November 2016 (9 pages)
MarcoValgimigli, FrancescoCosta, YuliyaLokhnygina, Robert M.Clare, LarsWallentin, David J.Moliterno, Paul W.Armstrong, Harvey D.White, ClaesHeld, Philip E.Aylward, FransVan de Werf, Robert A.Harrington, Kenneth W.Mahaffey, PierluigiTricociEur Heart J(2016)ehw525DOI: http://dx.doi.org/10.1093/eurheartj/ehw525First published online: 13 November 2016 (9 pages)
Philippe Jvan Rosendael, VasileiosKamperidis, William K.F.Kong, Alexander Rvan Rosendael, Frankvan der Kley, NinaAjmone Marsan, VictoriaDelgado, Jeroen JBaxEur Heart J(2016)ehw499DOI: http://dx.doi.org/10.1093/eurheartj/ehw499First published online: 2 November 2016 (10 pages)
FilippoCrea, C. NoelBairey Merz, John F.Beltrame, Juan CarlosKaski, HisaoOgawa, PeterOng, UdoSechtem, HiroakiShimokawa, Paolo G.CamiciEur Heart J(2016)ehw461DOI: http://dx.doi.org/10.1093/eurheartj/ehw461First published online: 23 October 2016 (5 pages)
LailaStaerk, Emil LoldrupFosbøl, Gregory Y.H.Lip, MortenLamberts, Anders NissenBonde, ChristianTorp-Pedersen, BriceOzenne, Thomas AlexanderGerds, Gunnar HilmarGislason, Jonas BjerringOlesenEur Heart J(2016)ehw496DOI: http://dx.doi.org/10.1093/eurheartj/ehw496First published online: 14 October 2016 (9 pages)
Thomas M.MacDonald, Chris J.Hawkey, IanFord, John J.V.McMurray, James M.Scheiman, JesperHallas, EvelynFindlay, Diederick E.Grobbee, F.D. RichardHobbs, Stuart H.Ralston, David M.Reid, Matthew R.Walters, JohnWebster, FrankRuschitzka, SirLewis D.Ritchie, SusanaPerez-Gutthann, EugeneConnolly, NicolaGreenlaw, AdamWilson, LiWei, Isla S.MackenzieEur Heart J(2016)ehw387DOI: http://dx.doi.org/10.1093/eurheartj/ehw387First published online: 4 October 2016 (9 pages)
Exosomes secreted by cardiosphere-derived cells (CDCs) were studied as a therapy for myocardial infarction (MI). In two different porcine models, exosomes from CDCs limited injury when given acutely and halted adverse remodelling when given in convalescent MI. Both models showed decreased scarring and improved function with intramyocardial delivery of exosomes. Cardiosphere-derived cell-secreted exosomes are a promising cell-free therapy for MI.
Patrick M.Moriarty, Klaus G.Parhofer, Stephan P.Babirak, Marc-AndreCornier, P. BartonDuell, BerndHohenstein, JosefLeebmann, WolfgangRamlow, VolkerSchettler, VinayaSimha, ElisabethSteinhagen-Thiessen, Paul D.Thompson, AnjaVogt, Berndtvon Stritzky, YunlingDu, GarenManvelianEur Heart J(2016)ehw388DOI: http://dx.doi.org/10.1093/eurheartj/ehw388First published online: 29 August 2016 (8 pages)
AlonEisen, Christopher P.Cannon, Michael A.Blazing, Erin A.Bohula, Jeong-GunPark, Sabina A.Murphy, Jennifer A.White, Robert P.Giugliano, EugeneBraunwaldEur Heart J(2016)ehw377DOI: http://dx.doi.org/10.1093/eurheartj/ehw377First published online: 28 August 2016 (9 pages)
ThomasMünzel, MetteSørensen, TommasoGori, Frank P.Schmidt, XiaoquanRao, Frank R.Brook, Lung ChiChen, Robert D.Brook, SanjayRajagopalanEur Heart J(2016)ehw294DOI: http://dx.doi.org/10.1093/eurheartj/ehw294First published online: 26 July 2016 (8 pages)
Andrew PaulDeFilippis, RebekahYoung, John W.McEvoy, Erin D.Michos, VeitSandfort, Richard A.Kronmal, Robyn L.McClelland, Michael J.BlahaEur Heart J(2016)ehw301DOI: http://dx.doi.org/10.1093/eurheartj/ehw301First published online: 19 July 2016 (11 pages)
To protect patients after MI by preserving cardiac function, the development of novel therapeutics is essential. In the current study, we assessed the effect of interference with NLRP3-inflammasome signalling on infarct size and cardiac function in a porcine MI model. For the first time, we show that cardiac function is preserved and infarct size is reduced by attenuating inflammation through NLRP3-inflammasome inhibition in a large animal MI model, making interference with this specific signalling pathway a promising target in MI patients.
Carlos A.Celis-Morales, Donald M.Lyall, JanaAnderson, StamatinaIliodromiti, YuFan, Uduakobong E.Ntuk, Daniel F.Mackay, Jill P.Pell, NaveedSattar, Jason M.R.GillEur Heart J(2016)ehw249DOI: http://dx.doi.org/10.1093/eurheartj/ehw249First published online: 6 July 2016 (7 pages)
Stratification for coronary events among patients with coronary artery disease is of considerable interest because of the potential to guide secondary preventive therapies. Our study proofs, that circulating miRNAs have the potential to improve risk stratification for secondary clinical events. In the future, these findings may result in risk stratification tools based on the prognostic value of miRNAs.
MercedesOrtiz, AlfonsoMartín, FernandoArribas, BlancaColl-Vinent, Carmendel Arco, RafaelPeinado, JesúsAlmendral
on behalf ofon Behalf of the PROCAMIO Study InvestigatorsEur Heart J(2016)ehw230DOI: http://dx.doi.org/10.1093/eurheartj/ehw230First published online: 28 June 2016 (8 pages)
Cardiomyocytes (CMs) generated from human induced pluripotent stem cells are an evolving platform to understand molecular disease mechanism and evaluate cardiovascular drugs. A major limitation of this system is that they represent a heterogeneous mix of ventricular-, atrial-, and nodal-like CMs. By expressing a voltage-sensitive fluorescent protein under the control of lineage-specific promoters, we developed a convenient system allowing high-throughput subtype-specific optical action potential (AP) imaging in these cells. This enables not only quantification of electrical phenotypes in patient-specific CMs but also subtype-specific investigation of drug effects, which may aid both drug development and safety pharmacology in the cardiovascular field.
Christoph K.Naber, PhilipUrban, Paul J.Ong, MarianoValdes-Chavarri, Alexandre A.Abizaid, Stuart J.Pocock, FrancoFabbiocchi, ChristopheDubois, SamuelCopt, SamanthaGreene, Marie-ClaudeMorice
on behalf offor the LEADERS FREE InvestigatorsEur Heart J(2016)ehw203DOI: http://dx.doi.org/10.1093/eurheartj/ehw203First published online: 17 May 2016 (9 pages)
IbrahimDanad, JackieSzymonifka, Jos W.R.Twisk, Bjarne L.Norgaard, Christopher K.Zarins, PaulKnaapen, James K.MinEur Heart J(2016)ehw095DOI: http://dx.doi.org/10.1093/eurheartj/ehw095First published online: 2 May 2016 (9 pages)
StefanAgewall, John F.Beltrame, Harmony R.Reynolds, AlexanderNiessner, GiuseppeRosano, Alida L. P.Caforio, RaffaeleDe Caterina, MarcoZimarino, MarcoRoffi, KeldKjeldsen, DanAtar, Juan C.Kaski, UdoSechtem, PerTornvall
on behalf of the WG on Cardiovascular PharmacotherapyEur Heart J(2016)ehw149DOI: http://dx.doi.org/10.1093/eurheartj/ehw149First published online: 28 April 2016 (11 pages)
GiuseppePatti, VittorioPengo, RossellaMarcucci, PlinioCirillo, GiuliaRenda, FrancescaSantilli, PaoloCalabrò, Alberto RanieriDe Caterina, IlariaCavallari, ElisabettaRicottini, Vito MaurizioParato, GiacomoZoppellaro, GiuseppeDi Gioia, PietroSedati, VincenzoCicchitti, GiovanniDavì, EnricaGolia, IvanaPariggiano, PaolaSimeone, RosannaAbbate, DomenicoPrisco, MarcoZimarino, FrancescoSofi, FelicitaAndreotti, RaffaeleDe Caterina
on behalf of the Working Group of Thrombosis of the Italian Society of CardiologyEur Heart J(2016)ehw159DOI: http://dx.doi.org/10.1093/eurheartj/ehw159First published online: 26 April 2016 (13 pages)
Christos V.Bourantas, Farouc A.Jaffer, Frank J.Gijsen, Gijsvan Soest, Sean P.Madden, Brian K.Courtney, Ali M.Fard, ErhanTenekecioglu, YapingZeng, Antonius F.W.van der Steen, StanislavEmelianov, JamesMuller, Peter H.Stone, LauraMarcu, Guillermo J.Tearney, Patrick W.SerruysEur Heart J(2016)ehw097DOI: http://dx.doi.org/10.1093/eurheartj/ehw097First published online: 26 April 2016 (15 pages)
A growing body of evidence suggests that myocardial fibrosis developing through the excessive accumulation of pathogenic myofibroblasts is a direct cause of impaired cardiac function in inflammatory heart diseases. Using the mouse model of inflammatory dilated cardiomyopathy, we describe a novel transforming growth factor-β (TGF-β)-dependent molecular mechanism controlling progression of post-inflammatory fibrogenesis. We describe how profibrotic cytokine TGF-β through activation of TGF-β-activated kinase 1 (TAK1) induces secretion of Wnt proteins, which activate the canonical Wnt pathway causing formation of pathogenic myofibroblasts. Our results indicate that pharmacological targeting of extracellular Wnts or the canonical Wnt pathway might represent a promising therapeutic option preventing accumulation of new pathogenic myofibroblasts. Such anti-fibrotic therapy in inflammatory cardiomyopathy patients potentially could prevent disease progression. Some researchers consider cardiac remodelling as a dynamic process with a substantial turnover of pathogenic cells. Therefore, inhibition of their de novo formation could eventually lead to resolution of the established fibrotic tissue and consequently to improvement of heart function in some patients. Furthermore, targeting of Wnts or Wnt pathway represents an attractive alternative for anti-TGF-β treatment by offering a broader range of available pharmacological compounds with well-defined function.
Inhibition of oxidative stress is considered a promising therapeutic strategy for pathological cardiac hypertrophy and heart failure. However, effective and specific targets for suppressing oxidative stress remain to be defined. Here, we demonstrate that Sirt4 promotes oxidative stress upon pathological stimulation, which results in an enhanced hypertrophic response in the heart. Furthermore, ROS inhibition abolishes the Sirt4-mediated aggravation of hypertrophy and rescues cardiac function in mice. Thus, suppression of Sirt4-mediated oxidative stress appears to be a potential therapeutic approach for pathological hypertrophy and heart failure.
This article describes experimental evidence for the fact that hypercoagulability—as caused by atrial fibrillation—induces pro-fibrotic and pro-inflammatory responses in adult atrial fibroblasts, that transgenic mice with hypercoagulability are more susceptible to atrial fibrillation than wild-type mice, and that the inhibition of hypercoagulability can partially prevent atrial remodelling in a well-characterized animal model of AF. These data show that the traditional causality of AF causing hypercoagulability may also hold in the opposite direction, i.e. that hypercoagulability has the potential to cause or promote AF. If confirmed in human studies, this new paradigm may have consequences for anticoagulant therapy in patients with or at risk for AF.
JoostBesseling, Johannes B.Reitsma, DanielGaudet, DianeBrisson, John J.P.Kastelein, G. KeesHovingh, Barbara A.HuttenEur Heart J(2016)ehw135DOI: http://dx.doi.org/10.1093/eurheartj/ehw135First published online: 3 April 2016 (10 pages)
Frederiekevan den Akker, Dries A.M.Feyen, Patriciavan den Hoogen, Linda W.van Laake, Esther C.M.van Eeuwijk, ImoHoefer, GerardPasterkamp, Steven A.J.Chamuleau, Paul F.Grundeman, Pieter A.Doevendans, Joost P.G.SluijterEur Heart J(2016)ehw056DOI: http://dx.doi.org/10.1093/eurheartj/ehw056First published online: 24 February 2016 (3 pages)
The circular RNA circ-Foxo3 is highly expressed in hearts of aged mice and patients and correlated with extensive senescence. Ectopic expression of circ-Foxo3 induced senescence and aggravated doxorubicin-induced cardiomyopathy. Silencing endogenous circ-Foxo3 inhibited senescence and relieved cardiomyopathy. This occurred through interaction with anti-senescent proteins ID-1 and E2F1, as well as anti-stress proteins FAK and HIF1α, leading to the relocation of these proteins in cytoplasm. Circ-Foxo3 may be targeted for drug development in the inhibition of tissue senescence.
Neutrophils are generally considered to play a detrimental role after post-myocardial infarction (MI) revascularization, but their role in myocardial ischaemia by itself has not been fully elucidated. Here, we provide novel evidence that neutrophils, despite being short-living innate immune responders, could contribute to improve cardiac healing and outcomes by influencing macrophage polarization towards a ‘reparative’ phenotype, via neutrophil gelatinase-associated lipocalin release. A better knowledge of the role of neutrophils in MI healing could help predicting the net results of neutrophil-targeted therapies in MI.
Epidemiological studies suggest a strong link between depression and incidence of acute coronary syndrome (ACS). Using a knock-in mouse carrying the BDNFVal66Met human polymorphism that phenocopies many of the human psychiatric-related symptoms, we show that modification of the BDNF gene suffices to enhance both a depressive and a prothrombotic/proinflammatory phenotype, and that SIRT1 activation by resveratrol prevents the prothrombotic/proinflammatory status. We also show that in humans the Met homozygosity associates with acute myocardial infarction, independently of age, sex, and major cardiovascular risk factors. Future studies will be directed to unveil the mechanistic link between BDNFVal66Met polymorphism, depression and ACS, thus opening the way to novel therapeutic approaches.