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Basic Research in Cardiology

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https://www.readbyqxmd.com/read/28101642/late-sodium-current-and-intracellular-ionic-homeostasis-in-acute-ischemia
#1
Carlotta Ronchi, Eleonora Torre, Riccardo Rizzetto, Joyce Bernardi, Marcella Rocchetti, Antonio Zaza
Blockade of the late Na(+) current (I NaL) protects from ischemia/reperfusion damage; nevertheless, information on changes in I NaL during acute ischemia and their effect on intracellular milieu is missing. I NaL, cytosolic Na(+) and Ca(2+) activities (Nacyt, Cacyt) were measured in isolated rat ventricular myocytes during 7 min of simulated ischemia (ISC); in all the conditions tested, effects consistently exerted by ranolazine (RAN) and tetrodotoxin (TTX) were interpreted as due to I NaL blockade. The results indicate that I NaL was enhanced during ISC in spite of changes in action potential (AP) contour; I NaL significantly contributed to Nacyt rise, but only marginally to Cacyt rise...
March 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28091727/intrinsic-cardiac-ganglia-and-acetylcholine-are-important-in-the-mechanism-of-ischaemic-preconditioning
#2
J M J Pickard, N Burke, S M Davidson, D M Yellon
This study aimed to investigate the role of the intrinsic cardiac nervous system in the mechanism of classical myocardial ischaemic preconditioning (IPC). Isolated perfused rat hearts were subjected to 35-min regional ischaemia and 60-min reperfusion. IPC was induced as three cycles of 5-min global ischaemia-reperfusion, and provided significant reduction in infarct size (IS/AAR = 14 ± 2% vs control IS/AAR = 48 ± 3%, p < 0.05). Treatment with the ganglionic antagonist, hexamethonium (50 μM), blocked IPC protection (IS/AAR = 37 ± 7%, p < 0...
March 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28013348/calpain-1-cleaves-and-inactivates-prostacyclin-synthase-in-mesenteric-arteries-from-diabetic-mice
#3
Voahanginirina Randriamboavonjy, Anastasia Kyselova, Amro Elgheznawy, Sven Zukunft, Ilka Wittig, Ingrid Fleming
Diabetes is associated with a number of co-morbidities including an increased risk of developing cardiovascular diseases. The activation of Ca(2+)-activated proteases of the calpain family has been implicated in platelet activation associated with diabetes and this study aimed to determine the role of calpain activation in the development of endothelial dysfunction. Diabetes induction in mice attenuated acetylcholine-induced relaxation of mesenteric artery rings, an effect prevented in mice receiving a calpain inhibitor...
January 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28013347/md2-mediates-angiotensin-ii-induced-cardiac-inflammation-and-remodeling-via-directly-binding-to-ang-ii-and-activating-tlr4-nf-%C3%AE%C2%BAb-signaling-pathway
#4
Jibo Han, Chunpeng Zou, Liqin Mei, Yali Zhang, Yuanyuan Qian, Shengban You, Yong Pan, Zheng Xu, Bin Bai, Weijian Huang, Guang Liang
Angiotensin II (Ang II) induces cardiac inflammation and remodeling. Emerging evidence indicates that Ang II may utilize the Toll-like receptor 4 (TLR4) signaling pathway in mediating pro-inflammatory and pro-fibrotic activities. However, the precise mechanism is poorly understood. Myeloid differentiation 2 (MD2), a molecule that physically binds to TLR4, confers lipopolysaccharide responsiveness and may also be involved in mediating the actions of Ang II. We hypothesize that MD2 plays an essential role in cardiac inflammation and remodeling induced by local Ang II, and inhibition of MD2 can attenuate Ang II-induced cardiac dysfunction...
January 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28005193/trek-1-k2p2-1-k-channels-are-suppressed-in-patients-with-atrial-fibrillation-and-heart-failure-and-provide-therapeutic-targets-for-rhythm-control
#5
Patrick Lugenbiel, Fabian Wenz, Pascal Syren, Pascal Geschwill, Katharina Govorov, Claudia Seyler, Derk Frank, Patrick A Schweizer, Jennifer Franke, Tanja Weis, Claus Bruehl, Bastian Schmack, Arjang Ruhparwar, Matthias Karck, Norbert Frey, Hugo A Katus, Dierk Thomas
Atrial fibrillation (AF) is the most common cardiac arrhythmia. Concomitant heart failure (HF) poses a particular therapeutic challenge and is associated with prolonged atrial electrical refractoriness compared with non-failing hearts. We hypothesized that downregulation of atrial repolarizing TREK-1 (K2P2.1) K(+) channels contributes to electrical remodeling during AF with HF, and that TREK-1 gene transfer would provide rhythm control via normalization of atrial effective refractory periods in this AF subset...
January 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28004242/targeted-myocardial-delivery-of-gdf11-gene-rejuvenates-the-aged-mouse-heart-and-enhances-myocardial-regeneration-after-ischemia-reperfusion-injury
#6
Guo-Qing Du, Zheng-Bo Shao, Jie Wu, Wen-Juan Yin, Shu-Hong Li, Jun Wu, Richard D Weisel, Jia-Wei Tian, Ren-Ke Li
Ischemic cardiac injury is the main contributor to heart failure, and the regenerative capacity of intrinsic stem cells plays an important role in tissue repair after injury. However, stem cells in aged individuals have reduced regenerative potential and aged tissues lack the capacity to renew. Growth differentiation factor 11 (GDF11), from the activin-transforming growth factor β superfamily, has been shown to promote stem cell activity and rejuvenation. We carried out non-invasive targeted delivery of the GDF11 gene to the heart using ultrasound-targeted microbubble destruction (UTMD) and cationic microbubble (CMB) to investigate the ability of GDF11 to rejuvenate the aged heart and improve tissue regeneration after injury...
January 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28000001/role-of-integrins-in-mediating-cardiac-fibroblast-cardiomyocyte-cross-talk-a-dynamic-relationship-in-cardiac-biology-and-pathophysiology
#7
REVIEW
Robert A Civitarese, Andras Kapus, Christopher A McCulloch, Kim A Connelly
Integrins are a family of heterodimeric proteins expressed by cardiac fibroblasts and cardiomyocytes that provide critical adhesive and signaling functions through their interactions with the extracellular matrix (ECM) and the actin cytoskeleton. These adhesive processes are important for paracrine signaling, ECM homeostasis and for the intercellular interactions that impact cardiac cell biology and pathophysiological adaptation in disease. Despite considerable progress, our understanding of the interplay between cardiac cells, the ECM and integrins remains largely elusive...
January 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27995364/transition-in-the-mechanism-of-flow-mediated-dilation-with-aging-and-development-of-coronary-artery-disease
#8
Andreas M Beyer, Natalya Zinkevich, Bradley Miller, Yanping Liu, April L Wittenburg, Michael Mitchell, Ralph Galdieri, Andrey Sorokin, David D Gutterman
In microvessels of patients with coronary artery disease (CAD), flow-mediated dilation (FMD) is largely dependent upon the endothelium-derived hyperpolarizing factor H2O2. The goal of this study is to examine the influence of age and presence or absence of disease on the mechanism of FMD. Human coronary or adipose arterioles (~150 µm diameter) were prepared for videomicroscopy. The effect of inhibiting COX [indomethacin (Indo) or NOS (L-NAME), eliminating H2O2 (polyethylene glycol-catalase (PEG-CAT)] or targeting a reduction in mitochondrial ROS with scavengers/inhibitors [Vitamin E (mtVitamin E); phenylboronic acid (mtPBA)] was determined in children aged 0-18 years; young adults 19-55 years; older adults >55 years without CAD, and similarly aged adults with CAD...
January 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27995363/unacylated-ghrelin-analog-prevents-myocardial-reperfusion-injury-independently-of-permeability-transition-pore
#9
Rania Harisseh, Bruno Pillot, Abdallah Gharib, Lionel Augeul, Noelle Gallo-Bona, René Ferrera, Joseph Loufouat, Thomas Delale, Soraya Allas, Thierry Abribat, Claire Crola Da Silva, Michel Ovize
Reperfusion injury is responsible for an important part of myocardial infarct establishment due notably to triggering cardiomyocytes death at the first minutes of reperfusion. AZP-531 is an optimized analog of unacylated ghrelin currently in clinical development in several metabolic diseases. We investigated a potential cardioprotective effect of AZP-531 in ischemia/reperfusion (IR) and the molecular underlying mechanism(s) involved in this protection. In vivo postconditioning with AZP-531 in C57BL6 mouse IR model decreased infarct size...
January 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27882430/identification-of-cardiovascular-risk-factors-associated-with-bone-marrow-cell-subsets-in-patients-with-stemi-a-biorepository-evaluation-from-the-cctrn-time-and-latetime-clinical-trials
#10
Ariadna Contreras, Aaron F Orozco, Micheline Resende, Robert C Schutt, Jay H Traverse, Timothy D Henry, Dejian Lai, John P Cooke, Roberto Bolli, Michelle L Cohen, Lem Moyé, Carl J Pepine, Phillip C Yang, Emerson C Perin, James T Willerson, Doris A Taylor
Autologous bone marrow mononuclear cell (BM-MNC) therapy for patients with ST-segment elevation myocardial infarction (STEMI) has produced inconsistent results, possibly due to BM-MNC product heterogeneity. Patient-specific cardiovascular risk factors (CRFs) may contribute to variations in BM-MNC composition. We sought to identify associations between BM-MNC subset frequencies and specific CRFs in STEMI patients. Bone marrow was collected from 191 STEMI patients enrolled in the CCTRN TIME and LateTIME trials...
January 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27864612/secretory-products-from-epicardial-adipose-tissue-from-patients-with-type-2-diabetes-impair-mitochondrial-%C3%AE-oxidation-in-cardiomyocytes-via-activation-of-the-cardiac-renin-angiotensin-system-and-induction-of-mir-208a
#11
Marcel Blumensatt, Pia Fahlbusch, Rebecca Hilgers, Marlies Bekaert, Daniella Herzfeld de Wiza, Payam Akhyari, Johannes B Ruige, D Margriet Ouwens
Secretory products from epicardial adipose tissue (EAT) from patients with type 2 diabetes (T2D) impair cardiomyocyte function. These changes associate with alterations in miRNA expression, including the induction of miR-208a. Recent studies suggest that activation of the cardiac-specific renin-angiotensin system (RAS) may affect cardiac energy metabolism via induction of miR-208a. This study investigated whether cardiomyocyte dysfunction induced by conditioned media (CM) from EAT-T2D involves activation of the RAS/miR-208a pathway...
January 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27837311/17%C3%AE-estradiol-induced-interaction-of-estrogen-receptor-%C3%AE-and-human-atrial-essential-myosin-light-chain-modulates-cardiac-contractile-function
#12
Karolin Duft, Miriam Schanz, Hang Pham, Ahmed Abdelwahab, Cindy Schriever, Georgios Kararigas, Elke Dworatzek, Mercy M Davidson, Vera Regitz-Zagrosek, Ingo Morano, Shokoufeh Mahmoodzadeh
Chronic increased workload of the human heart causes ventricular hypertrophy, re-expression of the atrial essential myosin light chain (hALC-1), and improved contractile function. Although hALC-1 is an important positive inotropic regulator of the human heart, little is known about its regulation. Therefore, we investigated the role of the sex hormone 17β-estradiol (E2) on hALC-1 gene expression, the underlying molecular mechanisms, and the impact of this regulatory process on cardiac contractile function...
January 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27783202/protective-and-pathogenic-roles-of-cd8-t-cells-in-atherosclerosis
#13
REVIEW
Clement Cochain, Alma Zernecke
Although infiltration of CD8(+) T cells in human atherosclerotic lesions has been described 30 years ago, the role of these cells in lesion development has long remained enigmatic. While experimental models hinted at their pro-atherogenic role based on circumstantial evidence, genetic mouse models of cytotoxic CD8(+) T cell-specific immune deficiency suggested no crucial role of these cells in lesion development. However, in recent years, more refined models of adoptive cell transfer, disruption of specific immune regulatory pathways or monoclonal antibody-mediated cell depletion have proposed both atheroprotective and pro-atherogenic functions for CD8(+) T cells in atherosclerosis...
November 2016: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27766474/ischaemic-conditioning-and-targeting-reperfusion-injury-a-30%C3%A2-year-voyage-of-discovery
#14
REVIEW
Derek J Hausenloy, Jose A Barrabes, Hans Erik Bøtker, Sean M Davidson, Fabio Di Lisa, James Downey, Thomas Engstrom, Péter Ferdinandy, Hector A Carbrera-Fuentes, Gerd Heusch, Borja Ibanez, Efstathios K Iliodromitis, Javier Inserte, Robert Jennings, Neena Kalia, Rajesh Kharbanda, Sandrine Lecour, Michael Marber, Tetsuji Miura, Michel Ovize, Miguel A Perez-Pinzon, Hans Michael Piper, Karin Przyklenk, Michael Rahbek Schmidt, Andrew Redington, Marisol Ruiz-Meana, Gemma Vilahur, Jakob Vinten-Johansen, Derek M Yellon, David Garcia-Dorado
To commemorate the auspicious occasion of the 30th anniversary of IPC, leading pioneers in the field of cardioprotection gathered in Barcelona in May 2016 to review and discuss the history of IPC, its evolution to IPost and RIC, myocardial reperfusion injury as a therapeutic target, and future targets and strategies for cardioprotection. This article provides an overview of the major topics discussed at this special meeting and underscores the huge importance and impact, the discovery of IPC has made in the field of cardiovascular research...
November 2016: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27743118/from-basic-mechanisms-to-clinical-applications-in-heart-protection-new-players-in-cardiovascular-diseases-and-cardiac-theranostics-meeting-report-from-the-third-international-symposium-on-new-frontiers-in-cardiovascular-research
#15
REVIEW
Hector A Cabrera-Fuentes, Julian Aragones, Jürgen Bernhagen, Andreas Boening, William A Boisvert, Hans E Bøtker, Heerajnarain Bulluck, Stuart Cook, Fabio Di Lisa, Felix B Engel, Bernd Engelmann, Fulvia Ferrazzi, Péter Ferdinandy, Alan Fong, Ingrid Fleming, Erich Gnaiger, Sauri Hernández-Reséndiz, Siavash Beikoghli Kalkhoran, Moo Hyun Kim, Sandrine Lecour, Elisa A Liehn, Michael S Marber, Manuel Mayr, Tetsuji Miura, Sang-Bing Ong, Karlheinz Peter, Daniel Sedding, Manvendra K Singh, M Saadeh Suleiman, Hans J Schnittler, Rainer Schulz, Winston Shim, Daniel Tello, Carl-Wilhelm Vogel, Malcolm Walker, Qilong Oscar Yang Li, Derek M Yellon, Derek J Hausenloy, Klaus T Preissner
In this meeting report, particularly addressing the topic of protection of the cardiovascular system from ischemia/reperfusion injury, highlights are presented that relate to conditioning strategies of the heart with respect to molecular mechanisms and outcome in patients' cohorts, the influence of co-morbidities and medications, as well as the contribution of innate immune reactions in cardioprotection. Moreover, developmental or systems biology approaches bear great potential in systematically uncovering unexpected components involved in ischemia-reperfusion injury or heart regeneration...
November 2016: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27743117/stiff-matrix-induces-switch-to-pure-%C3%AE-cardiac-myosin-heavy-chain-expression-in-human-esc-derived-cardiomyocytes
#16
Natalie Weber, Kristin Schwanke, Stephan Greten, Meike Wendland, Bogdan Iorga, Martin Fischer, Cornelia Geers-Knörr, Jan Hegermann, Christoph Wrede, Jan Fiedler, Henning Kempf, Annika Franke, Birgit Piep, Angelika Pfanne, Thomas Thum, Ulrich Martin, Bernhard Brenner, Robert Zweigerdt, Theresia Kraft
Human pluripotent stem cell (hPSC)-derived cardiomyocytes hold great potential for in vitro modeling of diseases like cardiomyopathies. Yet, knowledge about expression and functional impact of sarcomeric protein isoforms like the myosin heavy chain (MyHC) in hPSC-cardiomyocytes is scarce. We hypothesized that ventricular β-MyHC expression alters contraction and calcium kinetics and drives morphological and electrophysiological differentiation towards ventricular-like cardiomyocytes. To address this, we (1) generated human embryonic stem cell-derived cardiomyocytes (hESC-CMs) that switched towards exclusive β-MyHC, and (2) functionally and morphologically characterized these hESC-CMs at the single-cell level...
November 2016: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27704249/lrp5-canonical-wnt-signalling-and-healing-of-ischemic-myocardium
#17
M Borrell-Pages, G Vilahur, J C Romero, L Casaní, M T Bejar, L Badimon
LRP5 (low-density lipoprotein receptor-related protein 5) activates canonical Wnt signalling. LRP5 plays multiple roles including regulation of lipoprotein and cholesterol homeostasis as well as innate immunity cell function. However, it is not known whether LRP5 has a role in the myocardium. The aim of this study was to investigate LRP5 and Wnt signalling in myocardial remodelling after acute myocardial infarction (MI). Wnt protein levels were determined in a hypercholesterolemic porcine model of MI, in Lrp5 (-/-) C57Bl6 mice, in cultured cardiomyocytes and in human explanted hearts with previous MI episodes...
November 2016: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27683175/inhibition-of-cardiac-camkii-to-cure-heart-failure-step-by-step-towards-translation
#18
Friederike Cuello, Kristina Lorenz
No abstract text is available yet for this article.
November 2016: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27683174/inducible-cardiomyocyte-specific-deletion-of-cam-kinase-ii-protects-from-pressure-overload-induced-heart-failure
#19
Michael M Kreusser, Lorenz H Lehmann, Nora Wolf, Stanislav Keranov, Andreas Jungmann, Hermann-Josef Gröne, Oliver J Müller, Hugo A Katus, Johannes Backs
CaM kinase II (CaMKII) has been suggested to drive pathological cardiac remodeling and heart failure. However, the evidence provided so far is based on inhibitory strategies using chemical compounds and peptides that also exert off-target effects and followed exclusively preventive strategies. Therefore, the aim of this study was to investigate whether specific CaMKII inhibition after the onset of cardiac stress delays or reverses maladaptive cardiac remodeling and dysfunction. Combined genetic deletion of the two redundant CaMKII genes δ and γ was induced after the onset of overt heart failure as the result of pathological pressure overload induced by transverse aortic constriction (TAC)...
November 2016: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27665606/a-reproducible-protocol-for-neonatal-ischemic-injury-and-cardiac-regeneration-in-neonatal-mice
#20
Bernhard J Haubner, Thomas Schuetz, Josef M Penninger
Cardiac regeneration is one of the prime visions in cardiovascular research. The mouse neonatal apical resection and left anterior descending artery (LAD) ligation model introduced novel in vivo mammalian assays to study cardiac regeneration. However, recent reports and editorials discussed and critically questioned the value and technical reproducibility of the mouse neonatal myocardial infarction approach, making it paramount to develop and use a reproducible model system. We established a mouse neonatal myocardial infarction model by visually confirmed ligation of the LAD using microsurgery...
November 2016: Basic Research in Cardiology
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