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    16978 results match your criteria Circulation research[Journal]

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    Tbx20 Is Required in Mid-Gestation Cardiomyocytes and Plays a Central Role in Atrial Development.
    Circ Res 2018 Jun 14. Epub 2018 Jun 14.
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego
    Mutations in the transcription factor TBX20 are associated with congenital heart disease. Germline ablation of Tbx20 results in abnormal heart development and embryonic lethality by E9.5. Read More

    Mitochondrial ROS Drive Sudden Cardiac Death and Chronic Proteome Remodeling in Heart Failure.
    Circ Res 2018 Jun 13. Epub 2018 Jun 13.
    Cardiology, The Johns Hopkins University School of Medicine
    Despite increasing prevalence and incidence of heart failure (HF), therapeutic options remain limited. In early stages of HF, sudden cardiac death (SCD) from ventricular arrhythmias claims many lives. Reactive oxygen species (ROS) have been implicated in both arrhythmias and contractile dysfunction. Read More

    Effects of Repetitive Transendocardial CD34 Cell Transplantation in Patients with Non-Ischemic Dilated Cardiomyopathy.
    Circ Res 2018 Jun 7. Epub 2018 Jun 7.
    Stanford Cardiovascular Institute, Stanford University School of Medicine.
    Preclinical data in heart failure models suggest that repetitive stem cell therapy may be superior to single-dose cell administration. We investigated whether repetitive administration of CD34 cells is superior to single dose administration in patients with non-ischemic dilated cardiomyopathy (DCM). Of 66 patients with DCM, NYHA functional class III, and left ventricular ejection fraction (LVEF)< 40% enrolled in the study, 60 were randomly allocated to repetitive cell therapy (Group A, N=30), or single cell therapy (Group B, N=30). Read More

    Sleep Apnea and Cardiovascular Disease: An Enigmatic Risk Factor.
    Circ Res 2018 Jun;122(12):1741-1764
    From the University Health Network and Sinai Health System Division of Cardiology, Department of Medicine, University of Toronto, Ontario, Canada.
    Synchronization of molecular, metabolic, and cardiovascular circadian oscillations is fundamental to human health. Sleep-disordered breathing, which disrupts such temporal congruence, elicits hemodynamic, autonomic, chemical, and inflammatory disturbances with acute and long-term consequences for heart, brain, and circulatory and metabolic function. Sleep apnea afflicts a substantial proportion of adult men and women but is more prevalent in those with established cardiovascular diseases and especially fluid-retaining states. Read More

    NLRP3 Inflammasome and the IL-1 Pathway in Atherosclerosis.
    Circ Res 2018 Jun;122(12):1722-1740
    From the Institute of Innate Immunity, University Hospital Bonn, Germany (A.G., F.H., E.L.)
    Inflammation is an important driver of atherosclerosis, the underlying pathology of cardiovascular diseases. Therefore, therapeutic targeting of inflammatory pathways is suggested to improve cardiovascular outcomes in patients with cardiovascular diseases. This concept was recently proven by CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study), which demonstrated the therapeutic potential of the monoclonal IL (interleukin)-1β-neutralizing antibody canakinumab. Read More

    Role of Resident Stem Cells in Vessel Formation and Arteriosclerosis.
    Circ Res 2018 May;122(11):1608-1624
    From the Department of Cardiology, the First Affiliated Hospital, School of Medicine, Zhejiang University, China (L.Z., T.C., Q.X.)
    Vascular, resident stem cells are present in all 3 layers of the vessel wall; they play a role in vascular formation under physiological conditions and in remodeling in pathological situations. Throughout development and adult early life, resident stem cells participate in vessel formation through vasculogenesis and angiogenesis. In adults, the vascular stem cells are mostly quiescent in their niches but can be activated in response to injury and participate in endothelial repair and smooth muscle cell accumulation to form neointima. Read More

    Epigenomes in Cardiovascular Disease.
    Circ Res 2018 May;122(11):1586-1607
    From the Departments of Anesthesiology, Medicine, and Physiology, David Geffen School of Medicine, University of California, Los Angeles.
    If unifying principles could be revealed for how the same genome encodes different eukaryotic cells and for how genetic variability and environmental input are integrated to impact cardiovascular health, grand challenges in basic cell biology and translational medicine may succumb to experimental dissection. A rich body of work in model systems has implicated chromatin-modifying enzymes, DNA methylation, noncoding RNAs, and other transcriptome-shaping factors in adult health and in the development, progression, and mitigation of cardiovascular disease. Meanwhile, deployment of epigenomic tools, powered by next-generation sequencing technologies in cardiovascular models and human populations, has enabled description of epigenomic landscapes underpinning cellular function in the cardiovascular system. Read More

    Steroid Hormone Vitamin D: Implications for Cardiovascular Disease.
    Circ Res 2018 May;122(11):1576-1585
    From the Departments of Medicine (L.L.D., J.J.H., Y.T.).
    Understanding of vitamin D physiology is important because about half of the population is being diagnosed with deficiency and treated with supplements. Clinical guidelines were developed based on observational studies showing an association between low serum levels and increased cardiovascular risk. However, new randomized controlled trials have failed to confirm any cardiovascular benefit from supplementation in the general population. Read More

    YAP Controls Endothelial Activation and Vascular Inflammation Through TRAF6.
    Circ Res 2018 May 23. Epub 2018 May 23.
    Anesthesiology and Pharmacology, University of Illinois College of Medicine
    Microvascular inflammation and endothelial dysfunction secondary to unchecked activation of endothelium plays a critical role in the pathophysiology of sepsis and organ failure. The intrinsic signaling mechanisms responsible for dampening excessive activation of endothelial cells are not completely understood. To determine the central role of Yes-associated protein (YAP), the major transcriptional co-activator of the Hippo pathway, in modulating the strength and magnitude of endothelial activation and vascular inflammation. Read More

    Genetic Targeting of Organ-Specific Blood Vessels.
    Circ Res 2018 May 15. Epub 2018 May 15.
    Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
    Organs of the body require vascular networks to supply oxygen and nutrients and maintain physiological function. The blood vessels of different organs are structurally and functionally heterogeneous in nature. To more precisely dissect their distinct in vivo function in individual organs, without potential interference from off-site targets, it is necessary to genetically target them in an organ-specific manner. Read More

    Diabetes-Induced Cardiomyocyte Passive Stiffening Is Caused by Impaired Insulin-Dependent Titin Modification and Can Be Modulated by Neuregulin-1.
    Circ Res 2018 May 14. Epub 2018 May 14.
    Institute of Cardiovascular Physiology, Heinrich-Heine-University
    Increased titin-dependent cardiomyocyte tension is a hallmark of heart failure with preserved ejection fraction (HFpEF) associated with type-2 diabetes mellitus (T2DM). However, the insulin-related signaling pathways that modify titin-based cardiomyocyte tension, thereby contributing to modulation of diastolic function, are largely unknown. We aimed to determine how impaired insulin signaling affects titin expression and phosphorylation and thus increases passive cardiomyocyte tension, and whether metformin or neuregulin-1 can correct disturbed titin modifications and increased titin-based stiffness. Read More

    Calcium Signaling and Reactive Oxygen Species in Mitochondria.
    Circ Res 2018 May;122(10):1460-1478
    From the Comprehensive Heart Failure Center, University Clinic Würzburg, Germany.
    In heart failure, alterations of Na and Ca handling, energetic deficit, and oxidative stress in cardiac myocytes are important pathophysiological hallmarks. Mitochondria are central to these processes because they are the main source for ATP, but also reactive oxygen species (ROS), and their function is critically controlled by Ca During physiological variations of workload, mitochondrial Ca uptake is required to match energy supply to demand but also to keep the antioxidative capacity in a reduced state to prevent excessive emission of ROS. Mitochondria take up Ca via the mitochondrial Ca uniporter, which exists in a multiprotein complex whose molecular components were identified only recently. Read More

    Cardiovascular Effects of New Oral Glucose-Lowering Agents: DPP-4 and SGLT-2 Inhibitors.
    Circ Res 2018 May;122(10):1439-1459
    From the Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liège, Belgium (A.J.S.)
    Cardiovascular disease (CVD) is a major challenge in the management of type 2 diabetes mellitus. Glucose-lowering agents that reduce the risk of major cardiovascular events would be considered a major advance, as recently reported with liraglutide and semaglutide, 2 glucagon-like peptide-1 receptor agonists, and with empagliflozin and canagliflozin, 2 SGLT-2 (sodium-glucose cotransporter type 2) inhibitors, but not with DPP-4 (dipeptidyl peptidase-4) inhibitors. The present review is devoted to CV effects of new oral glucose-lowering agents. Read More

    PCSK9: From Basic Science Discoveries to Clinical Trials.
    Circ Res 2018 May;122(10):1420-1438
    From the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland.
    Unknown 15 years ago, PCSK9 (proprotein convertase subtilisin/kexin type 9) is now common parlance among scientists and clinicians interested in prevention and treatment of atherosclerotic cardiovascular disease. What makes this story so special is not its recent discovery nor the fact that it uncovered previously unknown biology but rather that these important scientific insights have been translated into an effective medical therapy in record time. Indeed, the translation of this discovery to novel therapeutic serves as one of the best examples of how genetic insights can be leveraged into intelligent target drug discovery. Read More

    Omics of Blood Pressure and Hypertension.
    Circ Res 2018 May;122(10):1409-1419
    From the College of Public Health, University of Kentucky, Lexington.
    Essential hypertension is a common, complex disorder affecting ≤1 billion adults globally. Blood pressure is a highly heritable trait, with ≤50% of the variation between individuals accounted for by familial relationships. Despite this strong heritability, determining the genetic architecture of hypertension in humans has proved challenging. Read More

    CRISPR-Mediated Gene Editing to Assess the Roles of Tet2 and Dnmt3a in Clonal Hematopoiesis and Cardiovascular Disease.
    Circ Res 2018 May 4. Epub 2018 May 4.
    Robert M. Berne Cardiovascular Research Center, University of Virginia
    Clonal hematopoiesis has been associated with increased mortality and cardiovascular disease (CVD). This condition can arise from somatic mutations in pre-leukemic driver genes within hematopoietic stem/progenitor cells (HSPC). Approximately 40 candidate driver genes have been identified, but mutations in only one of these genes, Ten-Eleven Translocation-2 (TET2), has been shown to casually contribute to CVD in murine models. Read More

    Plasma Biomarkers of Inflammation and Angiogenesis Predict Cerebral Cavernous Malformation Symptomatic Hemorrhage or Lesional Growth.
    Circ Res 2018 Jun 2;122(12):1716-1721. Epub 2018 May 2.
    From the Section of Neurosurgery, Department of Surgery, University of Chicago Medicine and Biological Sciences, IL (R.G., H.A.Z., J.K., M.D.F., Y.C., C.S., T.M., R.L., A.S., K.C., S.P., R.S., I.A.A.)
    Rationale: The clinical course of cerebral cavernous malformations is highly unpredictable, with few cross-sectional studies correlating proinflammatory genotypes and plasma biomarkers with prior disease severity.

    Objective: We hypothesize that a panel of 24 candidate plasma biomarkers, with a reported role in the physiopathology of cerebral cavernous malformations, may predict subsequent clinically relevant disease activity.

    Methods And Results: Plasma biomarkers were assessed in nonfasting peripheral venous blood collected from consecutive cerebral cavernous malformation subjects followed for 1 year after initial sample collection. Read More

    Rationale and Design of the CONCERT-HF Trial (Combination of Mesenchymal and c-kit Cardiac Stem Cells As Regenerative Therapy for Heart Failure).
    Circ Res 2018 Jun 27;122(12):1703-1715. Epub 2018 Apr 27.
    NIH, National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences, Bethesda, MD (R.F.E.).
    Rationale: Autologous bone marrow mesenchymal stem cells (MSCs) and c-kit cardiac progenitor cells (CPCs) are 2 promising cell types being evaluated for patients with heart failure (HF) secondary to ischemic cardiomyopathy. No information is available in humans about the relative efficacy of MSCs and CPCs and whether their combination is more efficacious than either cell type alone.

    Objective: CONCERT-HF (Combination of Mesenchymal and c-kit Cardiac Stem Cells As Regenerative Therapy for Heart Failure) is a phase II trial aimed at elucidating these issues by assessing the feasibility, safety, and efficacy of transendocardial administration of autologous MSCs and CPCs, alone and in combination, in patients with HF caused by chronic ischemic cardiomyopathy (coronary artery disease and old myocardial infarction). Read More

    Reactive Oxygen Species in Metabolic and Inflammatory Signaling.
    Circ Res 2018 Mar;122(6):877-902
    From the Division of Cardiology, Department of Medicine, Emory University, Atlanta GA.
    Reactive oxygen species (ROS) are well known for their role in mediating both physiological and pathophysiological signal transduction. Enzymes and subcellular compartments that typically produce ROS are associated with metabolic regulation, and diseases associated with metabolic dysfunction may be influenced by changes in redox balance. In this review, we summarize the current literature surrounding ROS and their role in metabolic and inflammatory regulation, focusing on ROS signal transduction and its relationship to disease progression. Read More

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