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https://www.readbyqxmd.com/read/28781147/durable-mechanical-circulatory-support-in-teenagers-and-adults-with-congenital-heart-disease-a-systematic-review
#1
Jill M Steiner, Eric V Krieger, Karen K Stout, April Stempien-Otero, Claudius Mahr, Nahush A Mokadam, Joshua L Hermsen
BACKGROUND: Heart failure is the leading cause of morbidity and mortality for adults with congenital heart disease (ACHD). Many patients are ineligible for transplantation, and those who are eligible often face long wait times with high wait-list morbidity. Durable mechanical circulatory support (MCS) may be an option for many patients. This systematic review evaluates the published literature on the use of durable MCS in teenagers and adults with congenital heart disease. METHODS: A comprehensive search of MEDLINE (PubMed), EMBASE, and the Cochrane Library was performed electronically in July 2015 and updated in March 2016, guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines...
October 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28705316/cell-specific-pathways-supporting-persistent-fibrosis-in-heart-failure
#2
Stephen D Farris, Creighton Don, Deri Helterline, Christopher Costa, Tabitha Plummer, Susanne Steffes, Claudius Mahr, Nahush A Mokadam, April Stempien-Otero
BACKGROUND: Only limited data exist describing the histologic and noncardiomyocyte function of human myocardium in end-stage heart failure (HF). OBJECTIVES: The authors sought to determine changes in noncardiomyocyte cellular activity in patients with end-stage HF after left ventricular assist device (LVAD)-induced remodeling to identify mechanisms impeding recovery. METHODS: Myocardium was obtained from subjects undergoing LVAD placement and/or heart transplantation...
July 18, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28255866/heart-failure-with-preserved-ejection-fraction-and-skeletal-muscle-physiology
#3
REVIEW
Stephen D Farris, Farid Moussavi-Harami, April Stempien-Otero
Heart failure with preserved ejection fraction (HFpEF) accounts for half of all heart failure in the USA, increases in prevalence with aging, and has no effective therapies. Intriguingly, the pathophysiology of HFpEF has many commonalities with the aged cardiovascular system including reductions in diastolic compliance, chronotropic defects, increased resistance in the peripheral vasculature, and poor energy substrate utilization. Decreased exercise capacity is a cardinal symptom of HFpEF. However, its severity is often out of proportion to changes in cardiac output...
March 2017: Heart Failure Reviews
https://www.readbyqxmd.com/read/27262672/cardiac-macrophages-adopt-profibrotic-m2-phenotype-in-infarcted-hearts-role-of-urokinase-plasminogen-activator
#4
Signe Carlson, Deri Helterline, Laura Asbe, Sarah Dupras, Elina Minami, Stephen Farris, April Stempien-Otero
BACKGROUND: Macrophages (mac) that over-express urokinase plasminogen activator (uPA) adopt a profibrotic M2 phenotype in the heart in association with cardiac fibrosis. We tested the hypothesis that cardiac macs are M2 polarized in infarcted mouse and human hearts and that polarization is dependent on mac-derived uPA. METHODS: Studies were performed using uninjured (UI) or infarcted (MI) hearts of uPA overexpressing (SR-uPA), uPA null, or nontransgenic littermate (Ntg) mice...
June 1, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27230735/effect-of-regional-competition-on-heart-transplant-waiting-list-outcomes
#5
Vidang P Nguyen, Raymond C Givens, Richard K Cheng, Nahush A Mokadam, Wayne C Levy, April Stempien-Otero, P Christian Schulze, Todd F Dardas
BACKGROUND: Heterogeneity of risk within heart transplant urgency designations is undesirable. Regional competition for donor hearts may contribute to this variation in risk. In this study we assessed whether an association exists between center competition and variation in event rates within status designations on the waiting list. METHODS: Our study sample included 20,237 adult transplant registrants initially listed between July 1, 2006 and July 1, 2013. Market competition was quantified using the Herfindahl-Hirshman Index (HHI) and number of centers within a donor service area (DSA) per 1 million people...
August 2016: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/27167848/molecular-networks-underlying-myofibroblast-fate-and-fibrosis
#6
REVIEW
April Stempien-Otero, Deok-Ho Kim, Jennifer Davis
Fibrotic remodeling is a hallmark of most forms of cardiovascular disease and a strong prognostic indicator of the advancement towards heart failure. Myofibroblasts, which are a heterogeneous cell-type specialized for extracellular matrix (ECM) secretion and tissue contraction, are the primary effectors of the heart's fibrotic response. This review is focused on defining myofibroblast physiology, its progenitor cell populations, and the core signaling network that orchestrates myofibroblast differentiation as a way of understanding the basic determinants of fibrotic disease in the heart and other tissues...
August 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/26316605/allogeneic-precursor-cells-for-systolic-heart-failure-a-need-for-mechanisms-in-humans
#7
EDITORIAL
Stephen Farris, April Stempien-Otero
No abstract text is available yet for this article.
August 28, 2015: Circulation Research
https://www.readbyqxmd.com/read/25857908/mechanisms-of-bone-marrow-derived-cell-therapy-in-ischemic-cardiomyopathy-with-left-ventricular-assist-device-bridge-to-transplant
#8
April Stempien-Otero, Deri Helterline, Tabitha Plummer, Stephen Farris, Andrew Prouse, Nayak Polissar, Derek Stanford, Nahush A Mokadam
BACKGROUND: Clinical trials report improvements in function and perfusion with direct injection of bone marrow cells into the hearts of patients with ischemic cardiomyopathy. Preclinical data suggest these cells improve vascular density, which would be expected to decrease fibrosis and inflammation. OBJECTIVES: The goal of this study was to test the hypothesis that bone marrow stem cells (CD34+) will improve histological measurements of vascularity, fibrosis, and inflammation in human subjects undergoing left ventricular assist device (LVAD) placement as a bridge to cardiac transplantation...
April 14, 2015: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/25498214/2-deoxy-adenosine-triphosphate-improves-contraction-in-human-end-stage-heart-failure
#9
Farid Moussavi-Harami, Maria V Razumova, Alice W Racca, Yuanhua Cheng, April Stempien-Otero, Michael Regnier
We are developing a novel treatment for heart failure by increasing myocardial 2 deoxy-ATP (dATP). Our studies in rodent models have shown that substitution of dATP for adenosine triphosphate (ATP) as the energy substrate in vitro or elevation of dATP in vivo increases myocardial contraction and that small increases in the native dATP pool of heart muscle are sufficient to improve cardiac function. Here we report, for the first time, the effect of dATP on human adult cardiac muscle contraction. We measured the contractile properties of chemically-demembranated multicellular ventricular wall preparations and isolated myofibrils from human subjects with end-stage heart failure...
February 2015: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/25290689/regulator-of-g-protein-signaling-5-is-a-marker-of-hepatic-stellate-cells-and-expression-mediates-response-to-liver-injury
#10
Arya J Bahrami, Jagadambika J Gunaje, Brian J Hayes, Kimberly J Riehle, Heidi L Kenerson, Raymond S Yeung, April S Stempien-Otero, Jean S Campbell, William M Mahoney
Liver fibrosis is mediated by hepatic stellate cells (HSCs), which respond to a variety of cytokine and growth factors to moderate the response to injury and create extracellular matrix at the site of injury. G-protein coupled receptor (GPCR)-mediated signaling, via endothelin-1 (ET-1) and angiotensin II (AngII), increases HSC contraction, migration and fibrogenesis. Regulator of G-protein signaling-5 (RGS5), an inhibitor of vasoactive GPCR agonists, functions to control GPCR-mediated contraction and hypertrophy in pericytes and smooth muscle cells (SMCs)...
2014: PloS One
https://www.readbyqxmd.com/read/24936447/thy-1-receptor-expression-differentiates-cardiosphere-derived-cells-with-divergent-cardiogenic-differentiation-potential
#11
Nuria Gago-Lopez, Obinna Awaji, Yiqiang Zhang, Christopher Ko, Ali Nsair, David Liem, April Stempien-Otero, W Robb MacLellan
Despite over a decade of intense research, the identity and differentiation potential of human adult cardiac progenitor cells (aCPC) remains controversial. Cardiospheres have been proposed as a means to expand aCPCs in vitro, but the identity of the progenitor cell within these 3D structures is unknown. We show that clones derived from cardiospheres could be subdivided based on expression of thymocyte differentiation antigen 1 (THY-1/CD90) into two distinct populations that exhibit divergent cardiac differentiation potential...
May 6, 2014: Stem Cell Reports
https://www.readbyqxmd.com/read/23536772/urokinase-plasminogen-activator-induces-pro-fibrotic-m2-phenotype-in-murine-cardiac-macrophages
#12
Jessica Meznarich, Laura Malchodi, Deri Helterline, Stephen A Ramsey, Kate Bertko, Tabitha Plummer, Abigail Plawman, Elizabeth Gold, April Stempien-Otero
OBJECTIVE: Inflammation and fibrosis are intertwined in multiple disease processes. We have previously found that over-expression of urokinase plasminogen activator in macrophages induces spontaneous macrophage accumulation and fibrosis specific to the heart in mice. Understanding the relationship between inflammation and fibrosis in the heart is critical to developing therapies for diverse myocardial diseases. Therefore, we sought to determine if uPA induces changes in macrophage function that promote cardiac collagen accumulation...
2013: PloS One
https://www.readbyqxmd.com/read/23391309/progenitor-cells-identified-by-pdgfr-alpha-expression-in-the-developing-and-diseased-human-heart
#13
James J H Chong, Hans Reinecke, Mineo Iwata, Beverly Torok-Storb, April Stempien-Otero, Charles E Murry
Platelet-derived growth factors (PDGFs) and their tyrosine kinase receptors play instrumental roles in embryonic organogenesis and diseases of adult organs. In particular, platelet-derived growth factor receptor-alpha (PDGFRα) is expressed by multipotent cardiovascular progenitors in mouse and human embryonic stem cell systems. Although cardiac PDGFRα expression has been studied in multiple species, little is known about its expression in the human heart. Using immunofluorescence, we analyzed PDGFRα expression in both human fetal and diseased adult hearts, finding strong expression in the interstitial cells of the epicardium, myocardium, and endocardium, as well as the coronary smooth muscle...
July 1, 2013: Stem Cells and Development
https://www.readbyqxmd.com/read/20380835/the-role-of-macrophage-derived-urokinase-plasminogen-activator-in-myocardial-infarct-repair-urokinase-attenuates-ventricular-remodeling
#14
Elina Minami, Chiara Castellani, Laura Malchodi, Jennifer Deem, Kate Bertko, Jessica Meznarich, Monja Dishmon, Charles E Murry, April Stempien-Otero
Cardiac plasmin activity is increased following myocardial ischemia. To test the hypothesis that macrophage-derived uPA is a key mediator of repair following myocardial infarction, we performed myocardial infarction on mice with macrophage-specific over-expression of uPA (SR-uPA mice). SR-uPA(+/0) mice and wild-type littermates were sacrificed at 5 days or 4 weeks after infarction and cardiac content of macrophages, collagen, and myofibroblasts was quantified. Cardiac function and dimensions were assessed by echocardiography at baseline and at 4 weeks post-infarction...
September 2010: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/19888538/constriction-of-carotid-arteries-by-urokinase-type-plasminogen-activator-requires-catalytic-activity-and-is-independent-of-nh-2-terminal-domains
#15
Philip G Massey, Shinji Tanaka, Joshua M Buckler, Bo Jiang, Anton McCourtie, Kun Qian, Clifford Tom, April Stempien-Otero, Shan Wen, Ian Luttrell, Kanchan Chitaley, David A Dichek
Urokinase-type plasminogen activator (uPA) is expressed at increased levels in stenotic, atherosclerotic human arteries. However, the biological roles of uPA in the artery wall are poorly understood. Previous studies associate uPA with both acute vasoconstriction and chronic vascular remodeling and attribute uPA-mediated vasoconstriction to the kringle - not the catalytic - domain of uPA. We used an in-vivo uPA overexpression model to test the hypothesis that uPA-induced vasoconstriction is a reversible vasomotor process that can be prevented - and uPA fibrinolytic activity preserved - by: 1) removing the growth factor and kringle domains; or 2) anchoring uPA to the endothelial surface...
November 2009: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/19325140/tgf-beta-1-limits-plaque-growth-stabilizes-plaque-structure-and-prevents-aortic-dilation-in-apolipoprotein-e-null-mice
#16
Andrew D Frutkin, Goro Otsuka, April Stempien-Otero, Casilde Sesti, Liang Du, Mia Jaffe, Helén L Dichek, Caroline J Pennington, Dylan R Edwards, Madeline Nieves-Cintrón, Daniel Minter, Michael Preusch, Jie Hong Hu, Julien C Marie, David A Dichek
OBJECTIVE: Impairment of transforming growth factor (TGF)-beta1 signaling accelerates atherosclerosis in experimental mice. However, it is uncertain whether increased TGF-beta1 expression would retard atherosclerosis. The role of TGF-beta1 in aneurysm formation is also controversial. We tested whether overexpression of active TGF-beta1 in hyperlipidemic mice affects atherogenesis and aortic dilation. METHODS AND RESULTS: We generated apolipoprotein E-null mice with transgenes that allow regulated overexpression of active TGF-beta1 in their hearts...
September 2009: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/18957535/plasminogen-mediates-the-atherogenic-effects-of-macrophage-expressed-urokinase-and-accelerates-atherosclerosis-in-apoe-knockout-mice
#17
Michal Kremen, Ranjini Krishnan, Isaac Emery, Jie Hong Hu, Katherine I Slezicki, Alyssa Wu, Kun Qian, Liang Du, Abigail Plawman, April Stempien-Otero, David A Dichek
Urokinase-type plasminogen activator (uPA) is expressed at elevated levels in atherosclerotic human arteries, primarily in macrophages. Plasminogen (Plg), the primary physiologic substrate of uPA, is present at significant levels in blood and interstitial fluid. Both uPA and Plg have activities that could affect atherosclerosis progression. Moreover, correlations between increased Plg activation and accelerated atherosclerosis are reported in several human studies. However, a coherent picture of the role of the uPA/Plg system in atherogenesis has not yet emerged, with at least one animal study suggesting that Plg is atheroprotective...
November 4, 2008: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/17996822/in-patients-with-heart-failure-elevated-soluble-tnf-receptor-1-is-associated-with-higher-risk-of-depression
#18
Alec J Moorman, Dariush Mozaffarian, Charles W Wilkinson, Richard L Lawler, George B McDonald, Barbara A Crane, John A Spertus, Joan E Russo, April S Stempien-Otero, Mark D Sullivan, Wayne C Levy
BACKGROUND: Pro-inflammatory cytokines may contribute to the development and progression of heart failure (HF) and are also implicated in depressive disorders. In this cross-sectional study, we investigated whether systemic inflammation, as assessed by circulating levels of inflammatory cytokines, was associated with comorbid depression in patients with heart failure. METHODS AND RESULTS: Baseline clinical variables, depression status, and inflammatory marker levels were measured in 129 ambulatory HF patients...
November 2007: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/17431190/mechanisms-of-tgf-beta1-induced-intimal-growth-plasminogen-independent-activities-of-plasminogen-activator-inhibitor-1-and-heterogeneous-origin-of-intimal-cells
#19
Goro Otsuka, April Stempien-Otero, Andrew D Frutkin, David A Dichek
Transforming growth factor (TGF)-beta(1) is a potent stimulator of intimal growth. We showed previously that TGF-beta(1) stimulates intimal growth through early upregulation of plasminogen activator inhibitor-1 (PAI-1) and, subsequently, PAI-1-dependent increases in cell migration and matrix accumulation. We also showed that PAI-1 negatively regulates TGF-beta(1) expression in the artery wall. Here we use plasminogen-deficient mice to test whether TGF-beta(1)-stimulated, PAI-1-dependent intimal growth and PAI-1 suppression of TGF-beta(1) expression are mediated through inhibition of plasminogen activation by PAI-1...
May 11, 2007: Circulation Research
https://www.readbyqxmd.com/read/17151822/confirmation-of-chagas-cardiomyopathy-following-heart-transplantation
#20
Binh An P Phan, Michael A Laflamme, April Stempien-Otero, Ajit P Limaye, Frederick S Buckner, Wayne C Levy
We report a case of Chagas' cardiomyopathy confirmed in a patient after heart transplantation. The patient initially presented with symptoms of congestive heart failure and was found to have positive serology for prior Trypanosoma cruzi infection. Despite optimal medical management, the patient had deterioration of his cardiac function and he underwent heart transplantation. Pathology examination of the explanted heart confirmed Chagas' cardiomyopathy. The cardiac sequelae of Chagas' disease include arrhythmias, aneurysm, thromboembolism, cardiomyopathy, and sudden death...
September 2006: Heart and Vessels
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