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JACC. Basic to Translational Science

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https://www.readbyqxmd.com/read/30175281/fake-news-alternative-facts-and-things-that-just-are-not-true-can-science-survive-the-post-truth-era
#1
EDITORIAL
Douglas L Mann
No abstract text is available yet for this article.
August 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/30175280/radiation-induced-endothelial-vascular-injury-a-review-of-possible-mechanisms
#2
REVIEW
Bhanu Prasad Venkatesulu, Lakshmi Shree Mahadevan, Maureen L Aliru, Xi Yang, Monica Himaani Bodd, Pankaj K Singh, Syed Wamique Yusuf, Jun-Ichi Abe, Sunil Krishnan
In radiation therapy for cancer, the therapeutic ratio represents an optimal balance between tumor control and normal tissue complications. As improvements in the therapeutic arsenal against cancer extend longevity, the importance of late effects of radiation increases, particularly those caused by vascular endothelial injury. Radiation both initiates and accelerates atherosclerosis, leading to vascular events like stroke, coronary artery disease, and peripheral artery disease. Increased levels of proinflammatory cytokines in the blood of long-term survivors of the atomic bomb suggest that radiation evokes a systemic inflammatory state responsible for chronic vascular side effects...
August 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/30175279/designer-approaches-for-g-protein-coupled-receptor-modulation-for-cardiovascular-disease
#3
REVIEW
Laurel A Grisanti, Sarah M Schumacher, Douglas G Tilley, Walter J Koch
The new horizon for cardiac therapy may lie beneath the surface, with the downstream mediators of G protein-coupled receptor (GPCR) activity. Targeted approaches have shown that receptor activation may be biased toward signaling through G proteins or through GPCR kinases (GRKs) and β-arrestins, with divergent functional outcomes. In addition to these canonical roles, numerous noncanonical activities of GRKs and β-arrestins have been demonstrated to modulate GPCR signaling at all levels of receptor activation and regulation...
August 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/30175278/pharmacogenetic-labeling-of-fda-approved-drugs-a-regulatory-retrospective
#4
REVIEW
Katarzyna Drozda, Michael A Pacanowski, Christian Grimstein, Issam Zineh
The U.S. Food and Drug Administration recently marked 10 years since first updating the labeling for warfarin (often referred to as the "poster child" of pharmacogenomics) to include information regarding the potential impact of CYP2C9 and VKORC1 genetic variation on warfarin dosing requirements and risks. Herein, we opine on the experience updating the warfarin labeling, highlighting more generally the enabling factors and challenges encountered when considering incorporation of pharmacogenomic information into the prescribing recommendations for already approved drugs...
August 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/30175277/expanded-patient-access-to-investigational-new-devices-review-of-emergency-and-nonemergency-expanded-use-custom-and-3d-printed-devices
#5
Gail A Van Norman
U.S. Food and Drug Administration (FDA) approval of Class III medical devices can take from 3 to 7 years. Although this is shorter than times for drug approvals, patients with serious or life-threatening diseases and disorders may not have time to wait for device approval to access needed treatments. The FDA has a number of pathways, similar to drug approval processes, for expanded use of unapproved medical devices in patients for whom no reasonable alternative therapy is available. Additionally, the FDA regulates the manufacture and use of "custom" medical devices-those made for use by 1 specific patient...
August 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/30175276/carvedilol-prevents-redox-inactivation-of-cardiomyocyte-%C3%AE-1-adrenergic-receptors
#6
Misun Park, Susan F Steinberg
The mechanism that leads to a decrease in β1 -adrenergic receptor (β1 AR) expression in the failing heart remains uncertain. This study shows that cardiomyocyte β1 AR expression and isoproterenol responsiveness decrease in response to oxidative stress. Studies of mechanisms show that the redox-dependent decrease in β1 AR expression is uniquely prevented by carvedilol and not other βAR ligands. Carvedilol also promotes the accumulation of N-terminally truncated β1 ARs that confer protection against doxorubicin-induced apoptosis in association with activation of protein kinase B...
August 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/30175275/unraveling-the-mechanisms-by-which-calpain-inhibition-prevents-heart-failure-development
#7
EDITORIAL
Xander H T Wehrens
No abstract text is available yet for this article.
August 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/30175274/targeting-calpain-for-heart-failure-therapy-implications-from-multiple-murine-models
#8
Yihui Wang, Biyi Chen, Chun-Kai Huang, Ang Guo, Jennifer Wu, Xiaoming Zhang, Rong Chen, Cheng Chen, William Kutschke, Robert M Weiss, Ryan L Boudreau, Kenneth B Margulies, Jiang Hong, Long-Sheng Song
Heart failure remains a major cause of morbidity and mortality in developed countries. There is still a strong need to devise new mechanism-based treatments for heart failure. Numerous studies have suggested the importance of the Ca2+ -dependent protease calpain in cardiac physiology and pathology. However, no drugs are currently under development or testing in human patients to target calpain for heart failure treatment. Herein the data demonstrate that inhibition of calpain activity protects against deleterious ultrastructural remodeling and cardiac dysfunction in multiple rodent models of heart failure, providing compelling evidence that calpain inhibition is a promising therapeutic strategy for heart failure treatment...
August 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/30175273/metabolic-suppression-of-hif-1%C3%AE-contributes-to-susceptibility-of-ischemic-injury-in-diabetic-hearts
#9
EDITORIAL
Adam De Jesus, Hsiang-Chun Chang, Hossein Ardehali
No abstract text is available yet for this article.
August 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/30175272/fatty-acids-prevent-hypoxia-inducible-factor-1%C3%AE-signaling-through-decreased-succinate-in-diabetes
#10
Michael S Dodd, Maria da Luz Sousa Fialho, Claudia N Montes Aparicio, Matthew Kerr, Kerstin N Timm, Julian L Griffin, Joost J F P Luiken, Jan F C Glatz, Damian J Tyler, Lisa C Heather
Hypoxia-inducible factor (HIF)-1α is essential following a myocardial infarction (MI), and diabetic patients have poorer prognosis post-MI. Could HIF-1α activation be abnormal in the diabetic heart, and could metabolism be causing this? Diabetic hearts had decreased HIF-1α protein following ischemia, and insulin-resistant cardiomyocytes had decreased HIF-1α-mediated signaling and adaptation to hypoxia. This was due to elevated fatty acid (FA) metabolism preventing HIF-1α protein stabilization. FAs exerted their effect by decreasing succinate concentrations, a HIF-1α activator that inhibits the regulatory HIF hydroxylase enzymes...
August 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/30175271/internal-bleeding-is-intraplaque-hemorrhage-a-decoration-or-a-driver
#11
EDITORIAL
Jean-Baptiste Michel, Peter Libby, Grégory Franck
No abstract text is available yet for this article.
August 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/30175270/novel-multiomics-profiling-of-human-carotid-atherosclerotic-plaques-and-plasma-reveals-biliverdin-reductase-b-as-a-marker-of-intraplaque-hemorrhage
#12
Ljubica Perisic Matic, Maria Jesus Iglesias, Mattias Vesterlund, Mariette Lengquist, Mun-Gwan Hong, Shanga Saieed, Laura Sanchez-Rivera, Martin Berg, Anton Razuvaev, Malin Kronqvist, Kent Lund, Kenneth Caidahl, Peter Gillgren, Fredrik Pontén, Mathias Uhlén, Jochen M Schwenk, Göran K Hansson, Gabrielle Paulsson-Berne, Erika Fagman, Joy Roy, Rebecka Hultgren, Göran Bergström, Janne Lehtiö, Jacob Odeberg, Ulf Hedin
Clinical tools to identify individuals with unstable atherosclerotic lesions are required to improve prevention of myocardial infarction and ischemic stroke. Here, a systems-based analysis of atherosclerotic plaques and plasma from patients undergoing carotid endarterectomy for stroke prevention was used to identify molecular signatures with a causal relationship to disease. Local plasma collected in the lesion proximity following clamping prior to arteriotomy was profiled together with matched peripheral plasma...
August 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/30175269/red-blood-cells-in-type-2-diabetes-impair-cardiac-post-ischemic-recovery-through-an-arginase-dependent-modulation-of-nitric-oxide-synthase-and-reactive-oxygen-species
#13
Jiangning Yang, Xiaowei Zheng, Ali Mahdi, Zhichao Zhou, Yahor Tratsiakovich, Tong Jiao, Attila Kiss, Oskar Kövamees, Michael Alvarsson, Sergiu-Bogdan Catrina, Jon O Lundberg, Kerstin Brismar, John Pernow
This study tested the hypothesis that red blood cell (RBC) arginase represents a potential therapeutic target in ischemia-reperfusion in type 2 diabetes. Post-ischemic cardiac recovery was impaired in hearts from db/db mice compared with wild-type hearts. RBCs from mice and patients with type 2 diabetes attenuated post-ischemic cardiac recovery of nondiabetic hearts. This impaired cardiac recovery was reversed by inhibition of RBCs arginase or nitric oxide synthase. The results suggest that RBCs from type 2 diabetics impair cardiac tolerance to ischemia-reperfusion via a pathway involving arginase activity and nitric oxide synthase-dependent oxidative stress...
August 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/30175268/ticagrelor-reduces-thromboinflammatory-markers-in-patients-with-pneumonia
#14
Travis R Sexton, Guoying Zhang, Tracy E Macaulay, Leigh A Callahan, Richard Charnigo, Olga A Vsevolozhskaya, Zhenyu Li, Susan Smyth
Despite treatment advances for sepsis and pneumonia, significant improvements in outcome have not been realized. Antiplatelet therapy may improve outcome in pneumonia and sepsis. In this study, the authors show that ticagrelor reduced leukocytes with attached platelets as well as the inflammatory biomarker interleukin (IL)-6. Pneumonia patients receiving ticagrelor required less supplemental oxygen and lung function tests trended toward improvement. Disruption of the P2Y12 receptor in a murine model protected against inflammatory response, lung permeability, and mortality...
August 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/30062229/partnerships-promote-translation-in-biomedicine
#15
EDITORIAL
Peter Libby
No abstract text is available yet for this article.
June 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/30062228/emerging-applications-of-virtual-reality-in-cardiovascular-medicine
#16
REVIEW
Jennifer N A Silva, Michael Southworth, Constantine Raptis, Jonathan Silva
Recently, rapid development in the mobile computing arena has allowed extended reality technologies to achieve performance levels that remove longstanding barriers to medical adoption. Importantly, head-mounted displays have become untethered and are light enough to be worn for extended periods of time, see-through displays allow the user to remain in his or her environment while interacting with digital content, and processing power has allowed displays to keep up with human perception to prevent motion sickness...
June 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/30062227/potentiation-of-insulin-signaling-contributes-to-heart-failure-in-type-2-diabetes-a-hypothesis-supported-by-both-mechanistic-studies-and-clinical-trials
#17
REVIEW
Milton Packer
The heightened risk of heart failure in type 2 diabetes cannot be explained by the occurrence of clinically overt myocardial ischemic events or hyperglycemia. Experimentally, insulin exerts detrimental effects on the heart, vasculature, kidneys, and adipose tissue that can lead to heart failure. In both randomized clinical trials and observational studies, antihyperglycemic drugs that act through insulin signaling (i.e., sulfonylureas, thiazolidinediones, and incretins) increase the risk or worsen the clinical course of heart failure, whereas drugs that ameliorate hyperinsulinemia and do not signal through insulin (i...
June 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/30062226/expanding-patient-access-to-investigational-new-drugs-overview-of-intermediate-and-widespread-treatment-investigational-new-drugs-and-emergency-authorization-in-public-health-emergencies
#18
Gail A Van Norman
Individual patients with life-threatening or severely debilitating diseases can petition the U.S. Food and Drug Administration (FDA) through their physicians to have expanded access (EA) to drugs that are in clinical trials but have not reached full FDA approval (the "single-patient" investigational new drug [IND] application). Additionally, recent state and federal laws-so-called "right to try legislation"-allow patients to approach drug companies directly for access prior to FDA approval...
June 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/30062225/a-morpholino-oligomer-therapy-regime-that-restores-mitochondrial-function-and-prevents-mdx-cardiomyopathy
#19
Helena M Viola, Victoria P A Johnstone, Abbie M Adams, Susan Fletcher, Livia C Hool
Current clinical trials demonstrate Duchenne muscular dystrophy (DMD) patients receiving phosphorodiamidate morpholino oligomer (PMO) therapy exhibit improved ambulation and stable pulmonary function; however, cardiac abnormalities remain. Utilizing the same PMO chemistry as current clinical trials, we have identified a non-toxic PMO treatment regimen that restores metabolic activity and prevents DMD cardiomyopathy. We propose that a treatment regimen of this nature may have the potential to significantly improve morbidity and mortality from DMD by improving ambulation, stabilizing pulmonary function, and preventing the development of cardiomyopathy...
June 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/30062224/in-vivo-reactive-oxygen-species-detection-with-a-novel-positron-emission-tomography-tracer-18-f-dhmt-allows-for-early-detection-of-anthracycline-induced-cardiotoxicity-in-rodents
#20
Nabil E Boutagy, Jing Wu, Zhengxi Cai, Wenjie Zhang, Carmen J Booth, Tassos C Kyriakides, Daniel Pfau, Tim Mulnix, Zhao Liu, Edward J Miller, Lawrence H Young, Richard E Carson, Yiyun Huang, Chi Liu, Albert J Sinusas
Reactive oxygen species (ROS) are involved in doxorubicin-induced cardiotoxicity. The authors investigated the efficacy of 18 F-DHMT, a marker of ROS, for early detection of doxorubicin-induced cardiotoxicity in rats. Echocardiography was performed at baseline and 4, 6, and 8 weeks post-doxorubicin initiation, whereas in vivo superoxide production was measured at 4 and 6 weeks with 18 F-DHMT positron emission tomography. Left ventricular ejection fraction (LVEF) was not significantly decreased until 6 weeks post-doxorubicin treatment, whereas myocardial superoxide production was significantly elevated at 4 weeks...
June 2018: JACC. Basic to Translational Science
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