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Cardiovascular Research

Giuseppe Ferrante, Gianluigi Condorelli
No abstract text is available yet for this article.
September 14, 2018: Cardiovascular Research
Sarah-Lena Puhl, Kate L Weeks, Alican Güran, Antonella Ranieri, Peter Boknik, Uwe Kirchhefer, Frank Ulrich Müller, Metin Avkiran
Aims: B56α is a protein phosphatase 2A (PP2A) regulatory subunit that is highly expressed in the heart. We previously reported that cardiomyocyte B56α localises to myofilaments under resting conditions and translocates to the cytosol in response to acute β-adrenergic receptor (β-AR) stimulation. Given the importance of reversible protein phosphorylation in modulating cardiac function during sympathetic stimulation, we hypothesised that loss of B56α in mice with targeted disruption of the gene encoding B56α (Ppp2r5a) would impact on cardiac responses to β-AR stimulation in vivo...
September 10, 2018: Cardiovascular Research
Hui Luo, Xiaohui Li, Tangzhiming Li, Lin Zhao, Jingni He, Lihuang Zha, Qiangqiang Qi, Zaixin Yu
Aims: A recent study reported the cardioprotective effects mediated by cardiac fibroblasts (CFs) during acute phase of ischemia-reperfusion injury. Little is known about whether exosomes/microvesicles mediate this beneficial effect and whether ischemia postconditioning (Postcon) can regulate this process. Here, we aimed to investigate the cardioprotective effect of CFs-exosomes/microvesicles and whether Psotcon can regulates this effect. Methods and Results: By using a transwells co-culture system, we found that hypoxia-reoxygenation (H/R) significantly increased the exosomes/microvesicles secretion of CFs and CFs protected H9C2 cells against H/R injury and Postcon could amplify these effects...
September 10, 2018: Cardiovascular Research
Dino Premilovac, Emily Attrill, Stephen Rattigan, Stephen M Richards, Jeong-A Kim, Michelle A Keske
Aims: Angiotensin II (AngII) is a potent vasoconstrictor implicated in both hypertension and insulin resistance. Insulin dilates the vasculature in skeletal muscle to increase microvascular blood flow and enhance glucose disposal. In the present study, we investigated whether acute AngII infusion interferes with insulin's microvascular and metabolic actions in skeletal muscle. Methods and Results: Adult, male Sprague-Dawley rats received a systemic infusion of either saline, AngII, insulin (hyperinsulinemic euglycemic clamp) or insulin (hyperinsulinemic euglycemic clamp) plus AngII...
September 5, 2018: Cardiovascular Research
Vajir Malek, Anil Bhanudas Gaikwad
Aims: LCZ696, a first-generation dual angiotensin receptor-neprilysin inhibitor (ARNi), is effective in treating heart failure patients. However, the role of ARNis in treating diabetic cardiomyopathy is poorly understood. This study evaluates the efficacy of a novel combination of telmisartan [angiotensin receptor blocker (ARB)] and thiorphan [neprilysin inhibitor (NEPi)] in ameliorating diabetic cardiomyopathy while, at the same time, exploring the relevant underlying molecular mechanism(s)...
September 4, 2018: Cardiovascular Research
Simon J Wilson, Thomas M Connolly, Gary Peters, Atalanta Ghosh, Maureen Johnson, David E Newby
Aims: JNJ-64179375 (hereafter JNJ-9375) is a first-in-class, highly specific, large molecule, exosite 1 thrombin inhibitor. In preclinical studies, JNJ-9375 demonstrated robust antithrombotic protection with a wider therapeutic index when compared to apixaban. The purpose of the present study was to examine for the first time the antiplatelet, anticoagulant and antithrombotic effects of JNJ-9375 in a translational model of ex vivo human thrombosis. Methods and Results: Fifteen healthy volunteers participated in a double-blind randomized crossover study of JNJ-9375 (2...
September 3, 2018: Cardiovascular Research
Yochai Birnbaum, Yumei Ye
No abstract text is available yet for this article.
September 3, 2018: Cardiovascular Research
Merry L Lindsey, Mira Jung, Andriy Yabluchanskiy, Presley L Cannon, Rugmani Padmanabhan Iyer, Elizabeth R Flynn, Kristine Y DeLeon-Pennell, Fritz M Valerio, Courtney L Harrison, Crystal M Ripplinger, Michael E Hall, Yonggang Ma
Aims: Macrophage phagocytosis of dead cells is a prerequisite for inflammation resolution. Because CXCL4 induces macrophage phagocytosis in vitro, we examined the impact of exogenous CXCL4 infusion on cardiac wound healing and macrophage phagocytosis following myocardial infarction (MI). Methods and Results: CXCL4 expression significantly increased in the infarct region beginning at day 3 post-MI, and macrophages were the predominant source. Adult male C57BL/6J mice were subjected to coronary artery occlusion, and MI mice were randomly infused with recombinant mouse CXCL4 or saline beginning at 24 h post-MI by mini-pump infusion...
August 29, 2018: Cardiovascular Research
Alain van Mil, Geerthe Margriet Balk, Klaus Neef, Jan Willem Buikema, Folkert W Asselbergs, Sean M Wu, Pieter A Doevendans, Joost P Sluijter
In the past few years, the use of specific cell types derived from induced pluripotent stem cells (iPSCs) has developed into a powerful approach to investigate the cellular pathophysiology of numerous diseases. Despite advances in therapy, heart disease continues to be one of the leading causes of death in the developed world. A major difficulty in unravelling the underlying cellular processes of heart disease is the extremely limited availability of viable human cardiac cells reflecting the pathological phenotype of the disease at various stages...
August 29, 2018: Cardiovascular Research
Raffaele Coppini, Cecilia Ferrantini
No abstract text is available yet for this article.
August 29, 2018: Cardiovascular Research
Carlos A Valverde, Gabriela Mazzocchi, Mariano N Di Carlo, Alejandro Ciocci Pardo, Nehuen Salas, María Ines Ragone, Juan I Felice, Alejandra Cely-Ortiz, Alicia E Consolini, Enrique Portiansky, Susana Mosca, Evangelia G Kranias, Xander H T Wehrens, Alicia Mattiazzi
Background: Abnormal Ca2+ release from the sarcoplasmic reticulum (SR), associated with CaMKII-dependent phosphorylation of RyR2 at Ser2814, has consistently been linked to arrhythmogenesis and ischemia/reperfusion-induced cell death. In contrast, the role played by SR Ca2+ uptake under these stress conditions remains controversial. We tested the hypothesis that an increase in SR Ca2+ uptake is able to attenuate reperfusion arrhythmias and cardiac injury elicited by increased RyR2-Ser2814 phosphorylation...
August 29, 2018: Cardiovascular Research
Randi J Parks, Sara Menazza, Kira M Holmström, Georgios Amanakis, Maria Fergusson, Hanley Ma, Angel M Aponte, Paolo Bernardi, Toren Finkel, Elizabeth Murphy
Aims: Knockout (KO) of the mitochondrial Ca2+ uniporter (MCU) in mice abrogates mitochondrial Ca2+ uptake and permeability transition pore (PTP) opening. However, hearts from global MCU-KO mice are not protected from ischemic injury. We aimed to investigate whether adaptive alterations occur in cell death signaling pathways in the hearts of global MCU-KO mice. Methods and results: First, we examined whether cell death may occur via an upregulation in necroptosis in MCU-KO mice...
August 27, 2018: Cardiovascular Research
Iwona Cicha, Cédric Chauvierre, Isabelle Texier, Claudia Cabella, Josbert M Metselaar, János Szebeni, Christoph Alexiou, François Rouzet, Gert Storm, Erik Stroes, Donald Bruce, Neil MacRitchie, Pasquale Maffia, Didier Letourneur
Cardiovascular diseases (CVD) account for nearly half of all deaths in Europe and almost 30% of global deaths. Despite the improved clinical management, cardiovascular mortality is predicted to rise in the next decades due to the increasing impact of aging, obesity and diabetes. The goal of emerging cardiovascular nanomedicine is to reduce the burden of CVD using nanoscale medical products and devices. However, the development of novel multicomponent nano-sized products poses multiple technical, ethical and regulatory challenges, which often obstruct their road to successful approval and use in clinical practice...
August 27, 2018: Cardiovascular Research
Zeynep Bastug-Özel, Peter T Wright, Axel E Kraft, Davor Pavlovic, Jacqueline Howie, Alexander Froese, William Fuller, Julia Gorelik, Michael J Shattock, Viacheslav O Nikolaev
Aims: Cyclic adenosine monophosphate (cAMP) regulates cardiac excitation-contraction coupling by acting in microdomains associated with sarcolemmal ion channels. However, local real time cAMP dynamics in such microdomains has not been visualized before. We sought to directly monitor cAMP in a microdomain formed around sodium-potassium ATPase (NKA) in healthy and failing cardiomyocytes and to better understand alterations of cAMP compartmentation in heart failure. Methods and Results: A novel Förster resonance energy transfer (FRET)-based biosensor termed PLM-Epac1 was developed by fusing a highly sensitive cAMP sensor Epac1-camps to the C-terminus of phospholemman (PLM)...
August 27, 2018: Cardiovascular Research
Man Xu, Run-Qing Xue, Yi Lu, Su-Yun Yong, Qing Wu, Yan-Ling Cui, Xiao-Ting Zuo, Xiao-Jiang Yu, Ming Zhao, Wei-Jin Zang
Aim: Cardiac hypertrophy is characterised by a shift in metabolic substrate utilisation, but the molecular events underlying the metabolic remodelling remain poorly understood. We explored metabolic remodelling and mitochondrial dysfunction in cardiac hypertrophy and investigated the cardioprotective effects of choline. Methods and Results: The experiments were conducted using a model of ventricular hypertrophy by partially banding the abdominal aorta of Sprague Dawley rats...
August 27, 2018: Cardiovascular Research
Yumeng Guo, Cheng Xu, Andy Wc Man, Bo Bai, Cuiting Luo, Yu Huang, Aimin Xu, Paul M Vanhoutte, Yu Wang
Rationale: Aged arteries are characterized by attenuated vasodilator and enhanced vasoconstrictor responses, which contribute to the development of diseases such as arterial hypertension, atherosclerosis and heart failure. SIRT1 is a longevity regulator exerting protective functions against vascular ageing, although the underlying mechanisms remain largely unknown. Objective: The present study was designed to elucidate the signaling pathways involved in endothelial SIRT1-mediated vasodilator responses in the arteries of young and old mice...
August 27, 2018: Cardiovascular Research
Sofia-Iris Bibli, Andreas Papapetropoulos, Efstathios K Iliodromitis, Andreas Daiber, Voahanginirina Randriamboavonjy, Sebastian Steven, Peter Brouckaert, Athanasia Chatzianastasiou, Kyriakos E Kypreos, Derek J Hausenloy, Ingrid Fleming, Ioanna Andreadou
Aims: Nitroglycerin (NTG) given prior to an ischemic insult exerts cardioprotective effects. However, whether administration of an acute low dose of NTG in a clinically relevant manner following an ischemic episode limits infarct size, has not yet been explored. Methods and Results: Adult mice were subjected to acute myocardial infarction in vivo and then treated with vehicle or low dose NTG prior to reperfusion. This treatment regimen minimized myocardial infarct size without affecting hemodynamic parameters, but the protective effect was absent in mice rendered tolerant to the drug...
August 27, 2018: Cardiovascular Research
(no author information available yet)
No abstract text is available yet for this article.
August 20, 2018: Cardiovascular Research
(no author information available yet)
No abstract text is available yet for this article.
August 20, 2018: Cardiovascular Research
Adela Herraiz-Martínez, Anna Llach, Carmen Tarifa, Jorge Gandía, Verónica Jiménez-Sabado, Estefanía Lozano-Velasco, Selma A Serra, Alexander Vallmitjana, Eduardo Vázquez Ruiz de Castroviejo, Raúl Benítez, Amelia Aranega, Christian Muñoz-Guijosa, Diego Franco, Juan Cinca, Leif Hove-Madsen
Aims: Single nucleotide polymorphisms on chromosome 4q25 have been associated with risk of atrial fibrillation (AF) but the exiguous knowledge of the mechanistic links between these risk variants and underlying electrophysiological alterations hampers their clinical utility. Here, we here tested the hypothesis that 4q25 risk variants cause alterations in the intracellular calcium homeostasis that predispose to spontaneous electrical activity. Methods and results: Western blotting, confocal calcium imaging, and patch-clamp techniques were used to identify mechanisms linking the 4q25 risk variants rs2200733T and rs13143308T to defects in the calcium homeostasis in human atrial myocytes...
August 14, 2018: Cardiovascular Research
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