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Basic Research in Cardiology

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https://www.readbyqxmd.com/read/28299467/cardiomyocyte-ogt-limits-ventricular-dysfunction-in-mice-following-pressure-overload-without-affecting-hypertrophy
#1
Sujith Dassanayaka, Robert E Brainard, Lewis J Watson, Bethany W Long, Kenneth R Brittian, Angelica M DeMartino, Allison L Aird, Anna M Gumpert, Timothy N Audam, Peter J Kilfoil, Senthilkumar Muthusamy, Tariq Hamid, Sumanth D Prabhu, Steven P Jones
The myocardial response to pressure overload involves coordination of multiple transcriptional, posttranscriptional, and metabolic cues. The previous studies show that one such metabolic cue, O-GlcNAc, is elevated in the pressure-overloaded heart, and the increase in O-GlcNAcylation is required for cardiomyocyte hypertrophy in vitro. Yet, it is not clear whether and how O-GlcNAcylation participates in the hypertrophic response in vivo. Here, we addressed this question using patient samples and a preclinical model of heart failure...
May 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28271186/suv39h1-mediated-sirt1-trans-repression-contributes-to-cardiac-ischemia-reperfusion-injury
#2
Guang Yang, Xinjian Zhang, Xinyu Weng, Peng Liang, Xin Dai, Sheng Zeng, Huihui Xu, Hailin Huan, Mingming Fang, Yuehua Li, Dachun Xu, Yong Xu
Ischemic reperfusion (I/R) contributes to deleterious cardiac remodeling and heart failure. The deacetylase SIRT1 has been shown to protect the heart from I/R injury. We examined the mechanism whereby I/R injury represses SIRT1 transcription in the myocardium. There was accumulation of trimethylated histone H3K9 on the proximal SIRT1 promoter in the myocardium in mice following I/R injury and in cultured cardiomyocytes exposed to hypoxia-reoxygenation (H/R). In accordance, the H3K9 trimethyltransferase SUV39H1 bound to the SIRT1 promoter and repressed SIRT1 transcription...
May 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28258299/vasopressors-induce-passive-pulmonary-hypertension-by-blood-redistribution-from-systemic-to-pulmonary-circulation
#3
Chunling Jiang, Hong Qian, Shuhua Luo, Jing Lin, Jerry Yu, Yajiao Li, Qi An, Nanfu Luo, Lei Du
Vasopressors are widely used in resuscitation, ventricular failure, and sepsis, and often induce pulmonary hypertension with undefined mechanisms. We hypothesize that vasopressor-induced pulmonary hypertension is caused by increased pulmonary blood volume and tested this hypothesis in dogs under general anesthesia. In normal hearts (model 1), phenylephrine (2.5 μg/kg/min) transiently increased right but decreased left cardiac output, associated with increased pulmonary blood volume (63% ± 11.8, P = 0...
May 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28258298/complement-factor-5-blockade-reduces-porcine-myocardial-infarction-size-and-improves-immediate-cardiac-function
#4
Soeren E Pischke, A Gustavsen, H L Orrem, K H Egge, F Courivaud, H Fontenelle, A Despont, A K Bongoni, R Rieben, T I Tønnessen, M A Nunn, H Scott, H Skulstad, A Barratt-Due, T E Mollnes
Inhibition of complement factor 5 (C5) reduced myocardial infarction in animal studies, while no benefit was found in clinical studies. Due to lack of cross-reactivity of clinically used C5 antibodies, different inhibitors were used in animal and clinical studies. Coversin (Ornithodoros moubata complement inhibitor, OmCI) blocks C5 cleavage and binds leukotriene B4 in humans and pigs. We hypothesized that inhibition of C5 before reperfusion will decrease infarct size and improve ventricular function in a porcine model of myocardial infarction...
May 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28238121/leukocyte-inos-is-required-for-inflammation-and-pathological-remodeling-in-ischemic-heart-failure
#5
Justin R Kingery, Tariq Hamid, Robert K Lewis, Mohamed Ameen Ismahil, Shyam S Bansal, Gregg Rokosh, Tim M Townes, Suzanne T Ildstad, Steven P Jones, Sumanth D Prabhu
In the failing heart, iNOS is expressed by both macrophages and cardiomyocytes. We hypothesized that inflammatory cell-localized iNOS exacerbates left ventricular (LV) remodeling. Wild-type (WT) C57BL/6 mice underwent total body irradiation and reconstitution with bone marrow from iNOS(-/-) mice (iNOS(-/-)c) or WT mice (WTc). Chimeric mice underwent coronary ligation to induce large infarction and ischemic heart failure (HF), or sham surgery. After 28 days, as compared with WTc sham mice, WTc HF mice exhibited significant (p < 0...
March 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28210871/repeated-doses-of-cardiac-mesenchymal-cells-are-therapeutically-superior-to-a-single-dose-in-mice-with-old-myocardial-infarction
#6
Yiru Guo, Marcin Wysoczynski, Yibing Nong, Alex Tomlin, Xiaoping Zhu, Anna M Gumpert, Marjan Nasr, Senthikumar Muthusamy, Hong Li, Michael Book, Abdur Khan, Kyung U Hong, Qianhong Li, Roberto Bolli
We have recently demonstrated that repeated administrations of c-kit(POS) cardiac progenitor cells (CPCs) have cumulative beneficial effects in rats with old myocardial infarction (MI), resulting in markedly greater improvement in left ventricular (LV) function compared with a single administration. To determine whether this paradigm applies to other species and cell types, mice with a 3-week-old MI received one or three doses of cardiac mesenchymal cells (CMCs), a novel cell type that we have recently described...
March 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28188434/bloodless-reperfusion-with-the-oxygen-carrier-hboc-201-in-acute-myocardial-infarction-a-novel-platform-for-cardioprotective-probes-delivery
#7
Jose M García-Ruiz, Carlos Galán-Arriola, Rodrigo Fernández-Jiménez, Jaume Aguero, Javier Sánchez-González, Ana García-Alvarez, Mario Nuno-Ayala, Gregory P Dubé, Zafiris Zafirelis, Gonzalo J López-Martín, Juan A Bernal, Enrique Lara-Pezzi, Valentín Fuster, Borja Ibáñez
Reperfusion, despite being required for myocardial salvage, is associated with additional injury. We hypothesize that infarct size (IS) will be reduced by a period of bloodless reperfusion with hemoglobin-based oxygen carriers (HBOC) before blood-flow restoration. In the pig model, we first characterized the impact of intracoronary perfusion with a fixed volume (600 ml) of a pre-oxygenated acellular HBOC, HBOC-201, on the healthy myocardium. HBOC-201 was administered through the lumen of the angioplasty balloon (i...
March 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28168403/carbon-monoxide-releasing-molecule-3-improves-myocardial-function-in-mice-with-sepsis-by-inhibiting-nlrp3-inflammasome-activation-in-cardiac-fibroblasts
#8
Wenbo Zhang, Aibin Tao, Ting Lan, Gediminas Cepinskas, Raymond Kao, Claudio M Martin, Tao Rui
The NLRP3 inflammasome is an intracellular multiple-protein complex that controls the maturation and release of interleukin (IL)-1β and IL-18. Endogenous carbon monoxide (CO) is anti-inflammatory. The aim of this study was to assess the effects/mechanisms of CO-releasing molecule-3 (CORM-3)-dependent modulation of the NLRP3 inflammasome in cardiac fibroblasts (CF) and its effect on myocardial function in sepsis. CF were treated with CORM-3 or inactive CORM-3 (iCORM-3) before NLRP3 inflammasome priming with lipopolysaccharides (LPS) or following activation with adenosine triphosphate (ATP)...
March 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28160133/cardioprotective-kinase-signaling-to-subsarcolemmal-and-interfibrillar-mitochondria-is-mediated-by-caveolar-structures
#9
Wylly Ramsés García-Niño, Francisco Correa, Julia Isabel Rodríguez-Barrena, Juan Carlos León-Contreras, Mabel Buelna-Chontal, Elizabeth Soria-Castro, Rogelio Hernández-Pando, José Pedraza-Chaverri, Cecilia Zazueta
The demonstration that caveolin-3 overexpression reduces myocardial ischemia/reperfusion injury and our own finding that multiprotein signaling complexes increase in mitochondria in association with caveolin-3 levels, led us to investigate the contribution of caveolae-driven extracellular signal-regulated kinases 1/2 (ERK1/2) on maintaining the function of cardiac mitochondrial subpopulations from reperfused hearts subjected to postconditioning (PostC). Rat hearts were isolated and subjected to ischemia/reperfusion and to PostC...
March 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28120038/compensatory-role-of-the-nbcn1-sodium-bicarbonate-cotransporter-on-ca-2-induced-mitochondrial-swelling-in-hypertrophic-hearts
#10
Lorena A Vargas, Fernanda Carrizo Velasquez, Bernardo V Alvarez
NBC Na(+)/HCO3(-) cotransporter (NBCn1) and NHE1 Na(+)/H(+) exchanger have been associated with cardiac disorders and recently located in coronary endothelial cells (CEC) and cardiomyocytes mitochondria, respectively. Mitochondrial NHE1 blockade delays permeability transition pore (MPTP) opening and reduces superoxide levels, two critical events exacerbated in cells of diseased hearts. Conversely, activation of NBCn1 prevented apoptosis in CEC subjected to ischemic stress. We characterized the role of the NHE1 and NBCn1 transporters in heart mitochondria from hypertrophic (SHR) and control (Wistar) rats...
March 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28116519/medium-chain-fatty-acids-modulate-myocardial-function-via-a-cardiac-odorant-receptor
#11
Nikolina Jovancevic, A Dendorfer, M Matzkies, M Kovarova, J C Heckmann, M Osterloh, M Boehm, L Weber, F Nguemo, J Semmler, J Hescheler, H Milting, E Schleicher, L Gelis, H Hatt
Several studies have demonstrated the expression of odorant receptors (OR) in various human tissues and their involvement in different physiological and pathophysiological processes. However, the functional role of ORs in the human heart is still unclear. Here, we firstly report the functional characterization of an OR in the human heart. Initial next-generation sequencing analysis revealed the OR expression pattern in the adult and fetal human heart and identified the fatty acid-sensing OR51E1 as the most highly expressed OR in both cardiac development stages...
March 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28101642/late-sodium-current-and-intracellular-ionic-homeostasis-in-acute-ischemia
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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