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JACC. Basic to Translational Science

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https://www.readbyqxmd.com/read/29963647/l-phenylalanine-restores-vascular-function-in-spontaneously-hypertensive-rats-through-activation-of-the-gch1-gfrp-complex
#1
Lamia Heikal, Anna Starr, Dania Hussein, Jesus Prieto-Lloret, Phil Aaronson, Lea Ann Dailey, Manasi Nandi
Reduced nitric oxide (NO) bioavailability correlates with impaired cardiovascular function. NO is extremely labile and has been challenging to develop as a therapeutic agent. However, NO bioavailability could be enhanced by pharmacologically targeting endogenous NO regulatory pathways. Tetrahydrobiopterin, an essential cofactor for NO production, is synthesized by GTP cyclohydrolase-1 (GCH1), which complexes with GCH1 feedback regulatory protein (GFRP). The dietary amino acid l-phenylalanine activates this complex, elevating vascular BH4 ...
June 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29876530/short-term-hemodynamic-effects-of-apelin-in-patients-with-pulmonary-arterial-hypertension
#2
Lauren Brash, Gareth D Barnes, Melanie J Brewis, A Colin Church, Simon J Gibbs, Luke S G E Howard, Geeshath Jayasekera, Martin K Johnson, Neil McGlinchey, Joelle Onorato, Joanne Simpson, Colin Stirrat, Stephen Thomson, Geoffrey Watson, Martin R Wilkins, Carrie Xu, David J Welsh, David E Newby, Andrew J Peacock
Apelin agonism causes systemic vasodilatation and increased cardiac contractility in humans, and improves pulmonary arterial hypertension (PAH) in animal models. Here, the authors examined the short-term pulmonary hemodynamic effects of systemic apelin infusion in patients with PAH. In a double-blind randomized crossover study, 19 patients with PAH received intravenous (Pyr1 )apelin-13 and matched saline placebo during invasive right heart catheterization. (Pyr1 )apelin-13 infusion caused a reduction in pulmonary vascular resistance and increased cardiac output...
April 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29938246/the-multifunctional-protein-bag3-a-novel-therapeutic-target-in-cardiovascular-disease
#3
Valerie D Myers, Joseph M McClung, JuFang Wang, Farzaneh G Tahrir, Manish K Gupta, Jennifer Gordon, Christopher H Kontos, Kamel Khalili, Joseph Y Cheung, Arthur M Feldman
The B-cell lymphoma 2-associated anthanogene (BAG3) protein is expressed most prominently in the heart, the skeletal muscle, and in many forms of cancer. In the heart, it serves as a co-chaperone with heat shock proteins in facilitating autophagy; binds to B-cell lymphoma 2, resulting in inhibition of apoptosis; attaches actin to the Z disk, providing structural support for the sarcomere; and links the α-adrenergic receptor with the L-type Ca2+ channel. When BAG3 is overexpressed in cancer cells, it facilitates prosurvival pathways that lead to insensitivity to chemotherapy, metastasis, cell migration, and invasiveness...
February 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29876529/kr%C3%A3-ppel-like-factors-crippling-and-un-crippling-metabolic-pathways
#4
Nina M Pollak, Matthew Hoffman, Ira J Goldberg, Konstantinos Drosatos
Krüppel-like factors (KLFs) are DNA-binding transcriptional factors that regulate various pathways that control metabolism and other cellular mechanisms. Various KLF isoforms have been associated with cellular, organ or systemic metabolism. Altered expression or activation of KLFs has been linked to metabolic abnormalities, such as obesity and diabetes, as well as with heart failure. In this review article we summarize the metabolic functions of KLFs, as well as the networks of different KLF isoforms that jointly regulate metabolism in health and disease...
February 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29732439/rad-gtpase-deletion-attenuates-post-ischemic-cardiac-dysfunction-and-remodeling
#5
Janet R Manning, Lakshman Chelvarajan, Bryana M Levitan, Catherine N Withers, Prabhakara R Nagareddy, Christopher M Haggerty, Brandon K Fornwalt, Erhe Gao, Himi Tripathi, Ahmed Abdel-Latif, Douglas A Andres, Jonathan Satin
The protein Rad interacts with the LTCC to modulate trigger Ca2+ , hence to govern contractility. Reducing Rad levels increases cardiac output. Ablation of Rad also attenuated the inflammatory response following acute myocardial infarction (AMI). Future studies to target deletion of Rad in the heart could be conducted to establish a novel treatment paradigm whereby pathologically stressed hearts would be given a safe, stable positive inotropic support without arrhythmias and without pathological structural remodeling...
February 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29600288/diffusion-tensor-cardiac-magnetic-resonance-reveals-exosomes-from-cardiosphere-derived-cells-preserve-myocardial-fiber-architecture-after-myocardial-infarction
#6
Christopher T Nguyen, James Dawkins, Xiaoming Bi, Eduardo Marbán, Debiao Li
The object of the study was to reveal the fiber microstructural response with diffusion tensor cardiac magnetic resonance after intramyocardial exosomes secreted by cardiosphere-derived cells (CDCEXO ) in chronic porcine myocardial infarction. Porcine with myocardial infarction underwent intramyocardial delivery of human CDCEXO and placebo in a randomized placebo-controlled study. Four weeks after injection, viability improved in the CDCEXO group, whereas myocardial fiber architecture and cardiac function were preserved...
February 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29445778/nadph-oxidase-4-driven-cardiac-macrophage-polarization-protects-against-myocardial-infarction-induced-remodeling
#7
Heloise Mongue-Din, Ashish S Patel, Yee H Looi, David J Grieve, Narayana Anilkumar, Alexander Sirker, Xuebin Dong, Alison C Brewer, Min Zhang, Alberto Smith, Ajay M Shah
The reactive oxygen species-generating enzyme NADPH oxidase 4 (Nox4) is up-regulated in the heart after myocardial infarction (MI). Mice with cardiomyocyte-targeted Nox4 overexpression (TG) displayed increased macrophages in the heart at baseline, with skewing toward an M2 phenotype compared with wild-type controls (WT). After MI, TG mice had a higher proportion of M2 macrophages along with higher survival, decreased cardiac remodeling, and better contractile function than wild-type mice. The post-MI increase in cardiac matrix metalloproteinase-2 activity was substantially blunted in TG mice...
December 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29354781/suppression-of-arrhythmia-by-enhancing-mitochondrial-ca-2-uptake-in-catecholaminergic-ventricular-tachycardia-models
#8
Maria K Schweitzer, Fabiola Wilting, Simon Sedej, Lisa Dreizehnter, Nathan J Dupper, Qinghai Tian, Alessandra Moretti, Ilaria My, Ohyun Kwon, Silvia G Priori, Karl-Ludwig Laugwitz, Ursula Storch, Peter Lipp, Andreas Breit, Michael Mederos Y Schnitzler, Thomas Gudermann, Johann Schredelseker
Cardiovascular disease-related deaths frequently arise from arrhythmias, but treatment options are limited due to perilous side effects of commonly used antiarrhythmic drugs. Cardiac rhythmicity strongly depends on cardiomyocyte Ca2+ handling and prevalent cardiac diseases are causally associated with perturbations in intracellular Ca2+ handling. Therefore, intracellular Ca2+ transporters are lead candidate structures for novel and safer antiarrhythmic therapies. Mitochondria and mitochondrial Ca2+ transport proteins are important regulators of cardiac Ca2+ handling...
December 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29349360/ultrasound-induced-microbubble-cavitation-for-the-treatment-of-catheterization-induced-vasospasm
#9
Shelby Kutty, Na Liu, Jia Zhou, Yunbin Xiao, Juefei Wu, David Danford, John Lof, Feng Xie, Thomas R Porter
No abstract text is available yet for this article.
December 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29333506/murine-models-of-heart-failure-with-preserved-ejection-fraction-a-fishing-expedition
#10
Maria Valero-Muñoz, Warren Backman, Flora Sam
Heart failure with preserved ejection fraction (HFpEF) is characterized by signs and symptoms of HF in the presence of a normal left ventricular (LV) ejection fraction (EF). Despite accounting for up to 50% of all clinical presentations of HF, the mechanisms implicated in HFpEF are poorly understood, thus precluding effective therapy. The pathophysiological heterogeneity in the HFpEF phenotype also contributes to this disease and likely to the absence of evidence-based therapies. Limited access to human samples and imperfect animal models that completely recapitulate the human HFpEF phenotype have impeded our understanding of the mechanistic underpinnings that exist in this disease...
December 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29520378/cardiosphere-derived-cells-demonstrate-metabolic-flexibility-that-is-influenced-by-adhesion-status
#11
Junaid Afzal, Angel Chan, Mehmet Fatih Karakas, Kirubel Woldemichael, Styliani Vakrou, Yufan Guan, Jeffrey Rathmell, Richard Wahl, Martin Pomper, D Brian Foster, Miguel A Aon, Benjamin Tsui, Brian O'Rourke, M Roselle Abraham
Adult stem cells demonstrate metabolic flexibility that is regulated by cell adhesion status. The authors demonstrate that adherent cells primarily utilize glycolysis, whereas suspended cells rely on oxidative phosphorylation for their ATP needs. Akt phosphorylation transduces adhesion-mediated regulation of energy metabolism, by regulating translocation of glucose transporters (GLUT1) to the cell membrane and thus, cellular glucose uptake and glycolysis. Cell dissociation, a pre-requisite for cell transplantation, leads to energetic stress, which is mediated by Akt dephosphorylation, downregulation of glucose uptake, and glycolysis...
October 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29430558/therapeutic-angiogenesis-for-peripheral-artery-disease-lessons-learned-in-translational-science
#12
Sunil R Iyer, Brian H Annex
Peripheral arterial disease (PAD) is a major health care problem. There have been limited advances in medical therapies, and a huge burden of symptomatic patients with intermittent claudication and critical limb ischemia who have limited treatment options. Angiogenesis is the growth and proliferation of blood vessels from existing vasculature. For approximately 2 decades, "therapeutic angiogenesis" has been studied as an investigational approach to treat patients with symptomatic PAD. Despite literally hundreds of positive preclinical studies, results from human clinical studies thus far have been disappointing...
October 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29806040/reply-apoptosis-a-double-edge-sword
#13
Brian R Weil, Rebeccah F Young, Xiaomeng Shen, Gen Suzuki, Jun Qu, Saurabh Malhotra, John M Canty
No abstract text is available yet for this article.
August 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29367953/pulsed-cavitational-ultrasound-softening-a-new-non-invasive-therapeutic-approach-of-calcified-bioprosthetic-valve-stenosis
#14
Olivier Villemain, Justine Robin, Alain Bel, Wojciech Kwiecinski, Patrick Bruneval, Bastien Arnal, Mathieu Rémond, Mickael Tanter, Emmanuel Messas, Mathieu Pernot
Background: The majority of prosthetic heart valves currently implanted are tissue valves that can be expected to calcify with time and eventually fail. Surgical or percutaneous redux valve replacement is associated with higher rate of complications. We propose a novel non-invasive therapeutic approach based on the use of pulsed cavitational ultrasound (PCU) to improve the valvular function of degenerative calcified bioprosthesis. Objectives: Our study aims to demonstrate in vitro and in vivo on an ovine model that PCU can significantly improve the bioprosthesis opening by softening remotely the calcified stiff cusps...
August 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29057376/p2y-12-receptor-function-and-response-to-cangrelor-in-neonates-with-cyanotic-congenital-heart-disease
#15
Elisabeth A Kaza, Matthew C Egalka, Hairu Zhou, Jianchun Chen, Denise Evans, Jayne Prats, Ruizhi Li, Scott L Diamond, Julie A Vincent, Emile A Bacha, Thomas G Diacovo
Shunt thrombosis remains a major cause of morbidity and mortality, especially during the initial palliation for single-ventricle physiology. The authors present evidence that the P2Y12 inhibitor cangrelor may fill a therapeutic void in thromboprophylaxis. They base this theory on results showing that platelets from neonatal patients with cyanotic congenital heart disease have a robust response to adenosine diphosphate and are amenable to P2Y12 inhibition with cangrelor. Unique to this study was their ability to establish drug efficacy in an avatar mouse model that permits the in vivo evaluation of human platelet-mediated thrombus formation illustrating that this P2Y12 inhibitor yields the intended biological response...
August 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28989985/cardiac-lymphatic-vessels-transport-and-healing-of-the-infarcted-heart
#16
Li-Hao Huang, Kory J Lavine, Gwendalyn J Randolph
The lymphatic vasculature plays a key role throughout the body in regulating tissue fluid homeostasis, lipid transport, and immune surveillance. Whereas it has been appreciated that the heart relies on lymphatic vessels to maintain fluid balance and that such balance must be tightly maintained to allow for normal cardiac output, it has only recently come to light that the lymphatic vasculature might serve as a therapeutic target to promote optimal healing following myocardial ischemia and infarction. We review the subject of cardiac lymphatic vessels herein and highlight studies that imply targeting of lymphatic vessel development or transport may serve as a promising avenue for future clinical application in the context of ischemic injury...
August 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28920099/fast-virtual-fractional-flow-reserve-based-upon-steady-state-computational-fluid-dynamics-analysis-results-from-the-virtu-fast-study
#17
Paul D Morris, Daniel Alejandro Silva Soto, Jeroen F A Feher, Dan Rafiroiu, Angela Lungu, Susheel Varma, Patricia V Lawford, D Rodney Hose, Julian P Gunn
Fractional flow reserve (FFR)-guided percutaneous intervention is superior to standard assessment but remains underused. The authors have developed a novel "pseudotransient" analysis protocol for computing virtual fractional flow reserve (vFFR) based upon angiographic images and steady-state computational fluid dynamics. This protocol generates vFFR results in 189 s (cf >24 h for transient analysis) using a desktop PC, with <1% error relative to that of full-transient computational fluid dynamics analysis...
August 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28920098/the-il-1ri-co-receptor-tilrr-frem1-isoform-2-controls-aberrant-inflammatory-responses-and-development-of-vascular-disease
#18
Sarah A Smith, Andriy O Samokhin, Mabruka Alfadi, Emer C Murphy, David Rhodes, W Mike L Holcombe, Endre Kiss-Toth, Robert F Storey, Siu-Pok Yee, Sheila E Francis, Eva E Qwarnstrom
Expression of the interleukin-1 receptor type I (IL-1RI) co-receptor Toll-like and interleukin-1 receptor regulator (TILRR) is significantly increased in blood monocytes following myocardial infarction and in the atherosclerotic plaque, whereas levels in healthy tissue are low. TILRR association with IL-1RI at these sites causes aberrant activation of inflammatory genes, which underlie progression of cardiovascular disease. The authors show that genetic deletion of TILRR or antibody blocking of TILRR function reduces development of atherosclerotic plaques...
August 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28920097/acute-cd47-blockade-during-ischemic-myocardial-reperfusion-enhances-phagocytosis-associated-cardiac-repair
#19
Shuang Zhang, Xin-Yi Yeap, Matthew DeBerge, Nivedita K Naresh, Kevin Wang, Zhengxin Jiang, Jane E Wilcox, Steven M White, John P Morrow, Paul W Burridge, Daniel Procissi, Evan A Scott, William Frazier, Edward B Thorp
Our data suggest that, after a myocardial infarction, integrin-associated protein CD47 on cardiac myocytes is elevated. In culture, increased CD47 on the surface of dying cardiomyocytes impairs phagocytic removal by immune cell macrophages. After myocardial ischemia and reperfusion, acute CD47 inhibition with blocking antibodies enhanced dead myocyte clearance by cardiac phagocytes and also improved the resolution of cardiac inflammation, reduced infarct size, and preserved cardiac contractile function. Early targeting of CD47 in the myocardium after reperfusion may be a new strategy to enhance wound repair in the ischemic heart...
August 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29152600/role-of-epinephrine-and-extracorporeal-membrane-oxygenation-in-the-management-of-ischemic-refractory-ventricular-fibrillation-a-randomized-trial-in-pigs
#20
Jason A Bartos, Sebastian Voicu, Timothy R Matsuura, Adamantios Tsangaris, Georgios Sideris, Brett A Oestreich, Stephen A George, Matthew Olson, Kadambari Chandra Shekar, Jennifer N Rees, Kathleen Carlson, Pierre Sebastian, Scott McKnite, Ganesh Raveendran, Tom P Aufderheide, Demetris Yannopoulos
xtracorporeal membrane oxygenation (ECMO) is used in cardiopulmonary resuscitation (CPR) of refractory cardiac arrest. We used a 2×2 study design to compare ECMO versus CPR and epinephrine versus placebo in a porcine model of ischemic refractory ventricular fibrillation (VF). Pigs underwent 5 minutes of untreated VF, 10 minutes of CPR, and were randomized to receive epinephrine versus placebo for another 35 minutes. Animals were further randomized to LAD reperfusion at minute 45 with ongoing CPR versus veno-arterial ECMO cannulation at minute 45 of CPR and subsequent LAD reperfusion...
June 2017: JACC. Basic to Translational Science
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