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Articles 1 - 30 of 33
Full-Text Articles in Medicine and Health Sciences
Does Anyone Remember "Fingerprints On An X-Ray?", Vincent L. Sorrell
Does Anyone Remember "Fingerprints On An X-Ray?", Vincent L. Sorrell
Gill Heart & Vascular Institute Faculty Publications
No abstract provided.
St-Segment Elevation In A Patient With Nausea, Vomiting, And Intracerebral Hemorrhage, Ranjan Banerjee, Dustin Hillerson, Steve W. Leung, Vincent L. Sorrell
St-Segment Elevation In A Patient With Nausea, Vomiting, And Intracerebral Hemorrhage, Ranjan Banerjee, Dustin Hillerson, Steve W. Leung, Vincent L. Sorrell
Gill Heart & Vascular Institute Faculty Publications
A 60-year-old man who presented with nausea, vomiting, and intracerebral hemorrhage developed inferior ST-segment elevation and angina. Coronary angiography showed no coronary obstruction. The patient was found to have a small bowel obstruction causing superior translocation of the heart. Relief of obstruction caused immediate resolution of electrocardiographic changes and symptoms. (Level of Difficulty: Beginner.)
Sex Differences In Trends And In-Hospital Outcomes Among Patients With Critical Limb Ischemia: A Nationwide Analysis, Ayman Elbadawi, Kirolos Barssoum, Michael Megaly, Devesh Rai, Ahmed Elsherbeeny, Hend Mansoor, Mehdi H. Shishehbor, Ahmed K. Abdel-Latif, Martha Gulati, Islam Y. Elgendy
Sex Differences In Trends And In-Hospital Outcomes Among Patients With Critical Limb Ischemia: A Nationwide Analysis, Ayman Elbadawi, Kirolos Barssoum, Michael Megaly, Devesh Rai, Ahmed Elsherbeeny, Hend Mansoor, Mehdi H. Shishehbor, Ahmed K. Abdel-Latif, Martha Gulati, Islam Y. Elgendy
Gill Heart & Vascular Institute Faculty Publications
Background
Critical limb ischemia (CLI) represents the most severe form of peripheral artery disease and is associated with significant mortality and morbidity. Contemporary data comparing the sex differences in trends, revascularization strategies, and in-hospital outcomes among patients with CLI are scarce.
Methods and Results
Using the National Inpatient Sample database years 2002 to 2015, we identified hospitalizations for CLI. Temporal trends for hospitalizations for CLI were evaluated. The differences in demographics, revascularization, and in‐hospital outcomes between both sexes were compared. Among 2 400 778 CLI hospitalizations, 43.6% were women. Women were older and had a higher prevalence of obesity, hypertension, …
Fontan-Associated Dyslipidemia, Adam M. Lubert, Tarek Alsaied, Joseph J. Palermo, Nadeem Anwar, Elaine M. Urbina, Nicole M. Brown, Craig Alexander, Hassan Almeneisi, Fred Wu, Andrew R. Leventhal, Nael Aldweib, Michael Mendelson, Alexander R. Opotowsky
Fontan-Associated Dyslipidemia, Adam M. Lubert, Tarek Alsaied, Joseph J. Palermo, Nadeem Anwar, Elaine M. Urbina, Nicole M. Brown, Craig Alexander, Hassan Almeneisi, Fred Wu, Andrew R. Leventhal, Nael Aldweib, Michael Mendelson, Alexander R. Opotowsky
Gill Heart & Vascular Institute Faculty Publications
Background
Hypocholesterolemia is a marker of liver disease, and patients with a Fontan circulation may have hypocholesterolemia secondary to Fontan-associated liver disease or inflammation. We investigated circulating lipids in adults with a Fontan circulation and assessed the associations with clinical characteristics and adverse events.
Methods and Results
We enrolled 164 outpatients with a Fontan circulation, aged ≥ 18 years, in the Boston Adult Congenital Heart Disease Biobank and compared them with 81 healthy controls. The outcome was a combined outcome of nonelective cardiovascular hospitalization or death. Participants with a Fontan (median age, 30.3 [interquartile range, 22.8–34.3 years], 42% women) had …
5Th Generation Vs 4Th Generation Troponin T In Predicting Major Adverse Cardiovascular Events And All-Cause Mortality In Patients Hospitalized For Non-Cardiac Indications: A Cohort Study, Vedant Gupta, Marc Paranzino, Talal Alnabelsi, Karam Ayoub, Joshua Eason, Andin Mullis, John R. Kotter, Andrew Parks, Levi May, Sethabhisha Nerusu, Chen Dai, Daniel Cleland, Steve W. Leung, Vincent L. Sorrell
5Th Generation Vs 4Th Generation Troponin T In Predicting Major Adverse Cardiovascular Events And All-Cause Mortality In Patients Hospitalized For Non-Cardiac Indications: A Cohort Study, Vedant Gupta, Marc Paranzino, Talal Alnabelsi, Karam Ayoub, Joshua Eason, Andin Mullis, John R. Kotter, Andrew Parks, Levi May, Sethabhisha Nerusu, Chen Dai, Daniel Cleland, Steve W. Leung, Vincent L. Sorrell
Gill Heart & Vascular Institute Faculty Publications
OBJECTIVE: The frequency and implications of an elevated cardiac troponin (4th or 5th generation TnT) in patients outside of the emergency department or presenting with non-cardiac conditions is unclear.
METHODS: Consecutive patients aged 18 years or older admitted for a primary non-cardiac condition who had the 4th generation TnT drawn had the 5th generation TnT run on the residual blood sample. Primary and secondary outcomes were all-cause mortality (ACM) and major adverse cardiovascular events (MACE) respectively at 1 year.
RESULTS: 918 patients were included (mean age 59.8 years, 55% male) in the cohort. 69% had elevated …
Cardiac Cell Therapy: Insights Into The Mechanisms Of Tissue Repair, Hsuan Peng, Kazuhiro Shindo, Renée R. Donahue, Ahmed K. Abdel-Latif
Cardiac Cell Therapy: Insights Into The Mechanisms Of Tissue Repair, Hsuan Peng, Kazuhiro Shindo, Renée R. Donahue, Ahmed K. Abdel-Latif
Gill Heart & Vascular Institute Faculty Publications
Stem cell-based cardiac therapies have been extensively studied in recent years. However, the efficacy of cell delivery, engraftment, and differentiation post-transplant remain continuous challenges and represent opportunities to further refine our current strategies. Despite limited long-term cardiac retention, stem cell treatment leads to sustained cardiac benefit following myocardial infarction (MI). This review summarizes the current knowledge on stem cell based cardiac immunomodulation by highlighting the cellular and molecular mechanisms of different immune responses to mesenchymal stem cells (MSCs) and their secretory factors. This review also addresses the clinical evidence in the field.
Therapeutic Development Of Group B Streptococcus Meningitis By Targeting A Host Cell Signaling Network Involving Egfr, Ningyu Zhu, Chengxian Zhang, Atish Prakash, Zheng Hou, Wei Liu, Weifeng She, Andrew J. Morris, Kwang Sik Kim
Therapeutic Development Of Group B Streptococcus Meningitis By Targeting A Host Cell Signaling Network Involving Egfr, Ningyu Zhu, Chengxian Zhang, Atish Prakash, Zheng Hou, Wei Liu, Weifeng She, Andrew J. Morris, Kwang Sik Kim
Gill Heart & Vascular Institute Faculty Publications
Group B Streptococcus (GBS) remains the most common Gram‐positive bacterium causing neonatal meningitis and GBS meningitis continues to be an important cause of mortality and morbidity. In this study, we showed that GBS penetration into the brain occurred initially in the meningeal and cortex capillaries, and exploits a defined host cell signaling network comprised of S1P2, EGFR, and CysLT1. GBS exploitation of such network in penetration of the blood–brain barrier was demonstrated by targeting S1P2, EGFR, and CysLT1 using pharmacological inhibition, gene knockout and knockdown cells, and gene knockout animals, as well as interrogation of the …
Comparative Effectiveness Of Anti-Inflammatory Drug Treatments In Coronary Heart Disease Patients: A Systematic Review And Network Meta-Analysis, Ivan Wudexi, Elica Shokri, Mohamed Abo-Aly, Kazuhiro Shindo, Ahmed Abdel-Latif
Comparative Effectiveness Of Anti-Inflammatory Drug Treatments In Coronary Heart Disease Patients: A Systematic Review And Network Meta-Analysis, Ivan Wudexi, Elica Shokri, Mohamed Abo-Aly, Kazuhiro Shindo, Ahmed Abdel-Latif
Gill Heart & Vascular Institute Faculty Publications
Introduction and Hypothesis. The role of inflammation is widely recognized in the pathogenesis of coronary artery disease. Research on animal models had shown the potential benefits of targeting specific inflammatory pathways. However, studies on human subjects are limited with small number of patients and no head-to-head comparisons. Methods. We conducted a network meta-analysis of randomized controlled trials that studied the effects of anti-inflammatory medications on cardiovascular outcomes of coronary artery disease patients. We searched the electronic database until March 2020 for relevant studies. Results. Nineteen trials examining the efficacy of eight anti-inflammatory medications (pexelizumab, anakinra, colchicine, darapladib, …
Predicting In-Hospital Mortality After An In-Hospital Cardiac Arrest: A Multivariate Analysis, Talal Alnabelsi, Rahul Annabathula, Julie Shelton, Marc Paranzino, Sarah Price Faulkner, Matthew Cook, Adam J. Dugan, Sethabhisha Nerusu, Susan S. Smyth, Vedant A. Gupta
Predicting In-Hospital Mortality After An In-Hospital Cardiac Arrest: A Multivariate Analysis, Talal Alnabelsi, Rahul Annabathula, Julie Shelton, Marc Paranzino, Sarah Price Faulkner, Matthew Cook, Adam J. Dugan, Sethabhisha Nerusu, Susan S. Smyth, Vedant A. Gupta
Gill Heart & Vascular Institute Faculty Publications
Aim of the study: Most survivors of an in-hospital cardiac arrest do not leave the hospital alive, and there is a need for a more patient-centered, holistic approach to the assessment of prognosis after an arrest. We sought to identify pre-, peri-, and post-arrest variables associated with in-hospital mortality amongst survivors of an in-hospital cardiac arrest.
Methods: This was a retrospective cohort study of patients ≥18 years of age who were resuscitated from an in-hospital arrest at our University Medical Center from January 1, 2013 to September 31, 2016. In-hospital mortality was chosen as a primary outcome and unfavorable discharge …
Liposomal Delivery Of Azithromycin Enhances Its Immunotherapeutic Efficacy And Reduces Toxicity In Myocardial Infarction, Ahmed Al-Darraji, Renée R. Donahue, Himi Tripathi, Hsuan Peng, Bryana M. Levitan, Lakshman Chelvarajan, Dalia Haydar, Erhe Gao, David Henson, John C. Gensel, David J. Feola, Vincent J. Venditto, Ahmed K. Abdel-Latif
Liposomal Delivery Of Azithromycin Enhances Its Immunotherapeutic Efficacy And Reduces Toxicity In Myocardial Infarction, Ahmed Al-Darraji, Renée R. Donahue, Himi Tripathi, Hsuan Peng, Bryana M. Levitan, Lakshman Chelvarajan, Dalia Haydar, Erhe Gao, David Henson, John C. Gensel, David J. Feola, Vincent J. Venditto, Ahmed K. Abdel-Latif
Gill Heart & Vascular Institute Faculty Publications
A growing body of evidence shows that altering the inflammatory response by alternative macrophage polarization is protective against complications related to acute myocardial infarction (MI). We have previously shown that oral azithromycin (AZM), initiated prior to MI, reduces inflammation and its negative sequelae on the myocardium. Here, we investigated the immunomodulatory role of a liposomal AZM formulation (L-AZM) in a clinically relevant model to enhance its therapeutic potency and avoid off-target effects. L-AZM (40 or 10 mg/kg, IV) was administered immediately post-MI and compared to free AZM (F-AZM). L-AZM reduced cardiac toxicity and associated mortality by 50% in mice. We …
Prognostic Role Of Elevated Myeloperoxidase In Patients With Acute Coronary Syndrome: A Systemic Review And Meta-Analysis, Andrew R. Kolodziej, Mohamed Abo-Aly, Eman Elsawalhy, Charles Campbell, Khaled M. Ziada, Ahmed K. Abdel-Latif
Prognostic Role Of Elevated Myeloperoxidase In Patients With Acute Coronary Syndrome: A Systemic Review And Meta-Analysis, Andrew R. Kolodziej, Mohamed Abo-Aly, Eman Elsawalhy, Charles Campbell, Khaled M. Ziada, Ahmed K. Abdel-Latif
Gill Heart & Vascular Institute Faculty Publications
Background. Myocardial inflammation following acute ischemic injury has been linked to poor cardiac remodeling and heart failure. Many studies have linked myeloperoxidase (MPO), a neutrophil and inflammatory marker, to cardiac inflammation in the setting of acute coronary syndrome (ACS). However, the prognostic role of MPO for adverse clinical outcomes in ACS patients has not been well established. Methods. MEDLINE and Cochrane databases were searched for studies from 1975 to March 2018 that investigated the prognostic value of serum MPO in ACS patients. Studies which have dichotomized patients into a high MPO group and a low MPO group reported clinical outcomes …
Adipose-Derived Autotaxin Regulates Inflammation And Steatosis Associated With Diet-Induced Obesity, J. Anthony Brandon, Maria Kraemer, Julia Vandra, Suchismita Halder, Margo F. Ubele, Andrew J. Morris, Susan S. Smyth
Adipose-Derived Autotaxin Regulates Inflammation And Steatosis Associated With Diet-Induced Obesity, J. Anthony Brandon, Maria Kraemer, Julia Vandra, Suchismita Halder, Margo F. Ubele, Andrew J. Morris, Susan S. Smyth
Gill Heart & Vascular Institute Faculty Publications
Autotaxin (ATX) is a secreted enzyme that generates the bioactive lipid lysophosphatidic acid (LPA). We generated mice with global inducible post-natal inactivation or adipose-specific loss of the Enpp2 gene encoding ATX. The animals are phenotypically unremarkable and exhibit differences in adipocyte size and adipose tissue expression of inflammatory genes after high fat feeding without gross differences in fat distribution or body mass. Surprisingly, both models of Enpp2- deficiency exhibited marked protection from high fat diet-induced hepatic steatosis. This phenotype was not associated with differences in dietary fat absorption but may be accounted for by differences in hepatic expression of …
Stroke Outcomes With Vorapaxar Versus Placebo In Patients With Acute Coronary Syndromes: Insights From The Tracer Trial, Leo Ungar, Robert M. Clare, Fatima Rodriguez, Bradley J Kolls, Paul W. Armstrong, Philip Aylward, Claes Held, David J. Moliterno, John Strony, Frans Van De Werf, Lars Wallentin, Harvey D. White, Pierluigi Tricoci, Robert A. Harrington, Kenneth W. Mahaffey, Chiara Melloni
Stroke Outcomes With Vorapaxar Versus Placebo In Patients With Acute Coronary Syndromes: Insights From The Tracer Trial, Leo Ungar, Robert M. Clare, Fatima Rodriguez, Bradley J Kolls, Paul W. Armstrong, Philip Aylward, Claes Held, David J. Moliterno, John Strony, Frans Van De Werf, Lars Wallentin, Harvey D. White, Pierluigi Tricoci, Robert A. Harrington, Kenneth W. Mahaffey, Chiara Melloni
Gill Heart & Vascular Institute Faculty Publications
Background—Vorapaxar, a protease‐activated receptor‐1 antagonist, is approved for secondary prevention of cardiovascular events but is associated with increased intracranial hemorrhage.
Methods and Results—TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) was a trial of vorapaxar versus placebo among patients with acute coronary syndrome. Strokes were adjudicated by a central events committee. Of 12 944 patients, 199 (1.5%) had ≥1 stroke during the study period (median follow‐up, 477 days). Four patients had a single stroke of unknown type; 195 patients had ≥1 stroke classified as hemorrhagic or nonhemorrhagic (165 nonhemorrhagic, 28 hemorrhagic, and 2 both). …
Wearable Cardioverter-Defibrillator After Myocardial Infarction, Jeffrey E. Olgin, Mark J. Pletcher, Eric Vittinghoff, Jerzy Wranicz, Rajesh Malik, Daniel P. Morin, Steven Zweibel, Alfred E. Buxton, Claude S. Elayi, Eugene H. Chung, Eric Rashba, Martin Borggrefe, Trisha F Hue, Carol Maguire, Feng Lin, Joel A. Simon, Stephen Hulley, Byron K. Lee, Vest Investigators
Wearable Cardioverter-Defibrillator After Myocardial Infarction, Jeffrey E. Olgin, Mark J. Pletcher, Eric Vittinghoff, Jerzy Wranicz, Rajesh Malik, Daniel P. Morin, Steven Zweibel, Alfred E. Buxton, Claude S. Elayi, Eugene H. Chung, Eric Rashba, Martin Borggrefe, Trisha F Hue, Carol Maguire, Feng Lin, Joel A. Simon, Stephen Hulley, Byron K. Lee, Vest Investigators
Gill Heart & Vascular Institute Faculty Publications
BACKGROUND
Despite the high rate of sudden death after myocardial infarction among patients with a low ejection fraction, implantable cardioverter–defibrillators are contraindicated until 40 to 90 days after myocardial infarction. Whether a wearable cardioverter–defibrillator would reduce the incidence of sudden death during this high-risk period is unclear.
METHODS
We randomly assigned (in a 2:1 ratio) patients with acute myocardial infarction and an ejection fraction of 35% or less to receive a wearable cardioverter–defibrillator plus guideline-directed therapy (the device group) or to receive only guideline-directed therapy (the control group). The primary outcome was the composite of sudden death or death from …
Ticagrelor Reduces Thromboinflammatory Markers In Patients With Pneumonia, Travis R. Sexton, Guoying Zhang, Tracy E. Macaulay, Leigh Ann Callahan, Richard Charnigo, Olga A. Vsevolozhskaya, Zhenyu Li, Susan S. Smyth
Ticagrelor Reduces Thromboinflammatory Markers In Patients With Pneumonia, Travis R. Sexton, Guoying Zhang, Tracy E. Macaulay, Leigh Ann Callahan, Richard Charnigo, Olga A. Vsevolozhskaya, Zhenyu Li, Susan S. Smyth
Gill Heart & Vascular Institute Faculty Publications
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. Results indicate a mechanistic link between platelets, leukocytes, and lung injury in settings of pneumonia and sepsis, and suggest possible therapeutic approaches …
Azithromycin Therapy Reduces Cardiac Inflammation And Mitigates Adverse Cardiac Remodeling After Myocardial Infarction: Potential Therapeutic Targets In Ischemic Heart Disease, Ahmed Al-Darraji, Dalia Haydar, Lakshman Chelvarajan, Himi Tripathi, Bryana R. Levitan, Erhe Gao, Vincent J. Venditto, John C. Gensel, David James Feola, Ahmed Abdel-Latif
Azithromycin Therapy Reduces Cardiac Inflammation And Mitigates Adverse Cardiac Remodeling After Myocardial Infarction: Potential Therapeutic Targets In Ischemic Heart Disease, Ahmed Al-Darraji, Dalia Haydar, Lakshman Chelvarajan, Himi Tripathi, Bryana R. Levitan, Erhe Gao, Vincent J. Venditto, John C. Gensel, David James Feola, Ahmed Abdel-Latif
Gill Heart & Vascular Institute Faculty Publications
Introduction
Acute myocardial infarction (MI) is a primary cause of worldwide morbidity and mortality. Macrophages are fundamental components of post-MI inflammation. Pro-inflammatory macrophages can lead to adverse cardiac remodeling and heart failure while anti-inflammatory/reparative macrophages enhance tissue healing. Shifting the balance between pro-inflammatory and reparative macrophages post-MI is a novel therapeutic strategy. Azithromycin (AZM), a commonly used macrolide antibiotic, polarizes macrophages towards the anti-inflammatory phenotype, as shown in animal and human studies. We hypothesized that AZM modulates post-MI inflammation and improves cardiac recovery.
Methods and results
Male WT mice (C57BL/6, 6–8 weeks old) were treated with either oral AZM (160 …
Lipid Phosphate Phosphatase 3 Regulates Adipocyte Sphingolipid Synthesis, But Not Developmental Adipogenesis Or Diet-Induced Obesity In Mice, Lorenzo Frederico, Liping Yang, Jason Brandon, Manikandan Panchatcharam, Hongmei Ren, Paul Mueller, Manjula Sunkara, Diana Escalante-Alcalde, Andrew J. Morris, Susan S. Smyth
Lipid Phosphate Phosphatase 3 Regulates Adipocyte Sphingolipid Synthesis, But Not Developmental Adipogenesis Or Diet-Induced Obesity In Mice, Lorenzo Frederico, Liping Yang, Jason Brandon, Manikandan Panchatcharam, Hongmei Ren, Paul Mueller, Manjula Sunkara, Diana Escalante-Alcalde, Andrew J. Morris, Susan S. Smyth
Gill Heart & Vascular Institute Faculty Publications
Dephosphorylation of phosphatidic acid (PA) is the penultimate step in triglyceride synthesis. Adipocytes express soluble intracellular PA-specific phosphatases (Lipins) and broader specificity membrane-associated lipid phosphate phosphatases (LPPs) that can also dephosphorylate PA. Inactivation of lipin1 causes lipodystrophy in mice due to defective developmental adipogenesis. Triglyceride synthesis is diminished but not ablated by inactivation of lipin1 in differentiated adipocytes implicating other PA phosphatases in this process. To investigate the possible role of LPPs in adipocyte lipid metabolism and signaling we made mice with adipocyte-targeted inactivation of LPP3 encoded by the Plpp3(Ppap2b) gene. Adipocyte LPP3 deficiency resulted in blunted …
Tfpiα Interacts With Fva And Fxa To Inhibit Prothrombinase During The Initiation Of Coagulation, Jeremy P. Wood, Helle H. Petersen, Bingke Yu, Xiaoai Wu, Ida Hilden, Alan E. Mast
Tfpiα Interacts With Fva And Fxa To Inhibit Prothrombinase During The Initiation Of Coagulation, Jeremy P. Wood, Helle H. Petersen, Bingke Yu, Xiaoai Wu, Ida Hilden, Alan E. Mast
Gill Heart & Vascular Institute Faculty Publications
Tissue factor pathway inhibitor α (TFPIα) inhibits prothrombinase, the thrombin-generating complex of factor Xa (FXa) and factor Va (FVa), during the initiation of coagulation. This inhibition requires binding of a conserved basic region within TFPIα to a conserved acidic region in FXa-activated and platelet-released FVa. In this study, the contribution of interactions between TFPIα and the FXa active site and FVa heavy chain to prothrombinase inhibition were examined to further define the inhibitory biochemistry. Removal of FXa active site binding by mutation or by deletion of the second Kunitz domain (K2) of TFPIα produced 17- or 34-fold weaker prothrombinase inhibition, …
Mobilization Studies In Mice Deficient In Sphingosine Kinase 2 Support A Crucial Role Of The Plasma Level Of Sphingosine-1-Phosphate In The Egress Of Hematopoietic Stem Progenitor Cells, Mateusz Adamiak, Lakshman Chelvarajan, Kevin R. Lynch, Webster L. Santos, Ahmed Abdel-Latif, Mariusz Z. Ratajczak
Mobilization Studies In Mice Deficient In Sphingosine Kinase 2 Support A Crucial Role Of The Plasma Level Of Sphingosine-1-Phosphate In The Egress Of Hematopoietic Stem Progenitor Cells, Mateusz Adamiak, Lakshman Chelvarajan, Kevin R. Lynch, Webster L. Santos, Ahmed Abdel-Latif, Mariusz Z. Ratajczak
Gill Heart & Vascular Institute Faculty Publications
Sphingosine-1-phosphate (S1P) is a bioactive lipid involved in cell signaling and, if released from cells, also plays a crucial role in regulating the trafficking of lympho-hematopoietic cells, including primitive hematopoietic stem/progenitor cells (HSPCs). It has been demonstrated that S1P chemoattracts HSPCs, and its level in peripheral blood creates a gradient directing egress of these cells during mobilization. In this paper we analyzed hematopoiesis in mice deficient in sphingosine kinase 2 (Sphk2-KO mice) and studied the effect of this mutation on plasma S1P levels. We found that Sphk2-KO mice have normal hematopoiesis, and, in contrast to Sphk1-KO mice, the circulating S1P …
Snaring Of The Right Ventricular Lead During Cavotricuspid Isthmus Ablation, Yousef Darrat, Morales X. Gustavo, Cristen Kelly Waespe, John C. Gurley, Samy-Claude Elayi
Snaring Of The Right Ventricular Lead During Cavotricuspid Isthmus Ablation, Yousef Darrat, Morales X. Gustavo, Cristen Kelly Waespe, John C. Gurley, Samy-Claude Elayi
Gill Heart & Vascular Institute Faculty Publications
The presence of a right ventricular (RV) lead may interfere with cavotricuspid isthmus (CTI) ablation. We present a new option of lifting the RV lead from the CTI allowing a successful ablation of a CTI-dependent flutter without compromising lead integrity and functionality.
Steroid Binding To Autotaxin Links Bile Salts And Lysophosphatidic Acid Signalling, Willem-Jan Keune, Jens Hausmann, Ruth Bolier, Dagmar Tolenaars, Andreas Kremer, Tatjana Heidebrecht, Robbie P. Joosten, Manjula Sunkara, Andrew J. Morris, Elisa Matas-Rico, Wouter H. Moolenaar, Ronald P. Oude Elferink, Anastassis Perrakis
Steroid Binding To Autotaxin Links Bile Salts And Lysophosphatidic Acid Signalling, Willem-Jan Keune, Jens Hausmann, Ruth Bolier, Dagmar Tolenaars, Andreas Kremer, Tatjana Heidebrecht, Robbie P. Joosten, Manjula Sunkara, Andrew J. Morris, Elisa Matas-Rico, Wouter H. Moolenaar, Ronald P. Oude Elferink, Anastassis Perrakis
Gill Heart & Vascular Institute Faculty Publications
Autotaxin (ATX) generates the lipid mediator lysophosphatidic acid (LPA). ATX-LPA signalling is involved in multiple biological and pathophysiological processes, including vasculogenesis, fibrosis, cholestatic pruritus and tumour progression. ATX has a tripartite active site, combining a hydrophilic groove, a hydrophobic lipid-binding pocket and a tunnel of unclear function. We present crystal structures of rat ATX bound to 7α-hydroxycholesterol and the bile salt tauroursodeoxycholate (TUDCA), showing how the tunnel selectively binds steroids. A structure of ATX simultaneously harbouring TUDCA in the tunnel and LPA in the pocket, together with kinetic analysis, reveals that bile salts act as partial non-competitive inhibitors …
Molecular Cause And Functional Impact Of Altered Synaptic Lipid Signaling Due To A Prg-1 Gene Snp, Johannes Vogt, Jenq-Wei Yang, Arian Mobascher, Jin Cheng, Yunbo Li, Xingfeng Liu, Jan Baumgart, Carine Thalman, Sergei Kirischuk, Petr Unichenko, Guilherme Horta, Konstantin Radyushkin, Albrecht Stroh, Sebastian Richers, Nassim Sahragard, Ute Distler, Stefan Tenzer, Lianyong Qiao, Klaus Lieb, Oliver Tüscher, Harald Binder, Nerea Ferreiros, Irmgard Tegeder, Andrew J. Morris, Sergiu Gropa, Peter Nürnberg, Mohammad R. Toliat, Georg Winterer, Heiko J. Luhmann, Jisen Huai, Robert Nitsch
Molecular Cause And Functional Impact Of Altered Synaptic Lipid Signaling Due To A Prg-1 Gene Snp, Johannes Vogt, Jenq-Wei Yang, Arian Mobascher, Jin Cheng, Yunbo Li, Xingfeng Liu, Jan Baumgart, Carine Thalman, Sergei Kirischuk, Petr Unichenko, Guilherme Horta, Konstantin Radyushkin, Albrecht Stroh, Sebastian Richers, Nassim Sahragard, Ute Distler, Stefan Tenzer, Lianyong Qiao, Klaus Lieb, Oliver Tüscher, Harald Binder, Nerea Ferreiros, Irmgard Tegeder, Andrew J. Morris, Sergiu Gropa, Peter Nürnberg, Mohammad R. Toliat, Georg Winterer, Heiko J. Luhmann, Jisen Huai, Robert Nitsch
Gill Heart & Vascular Institute Faculty Publications
Loss of plasticity‐related gene 1 (PRG‐1), which regulates synaptic phospholipid signaling, leads to hyperexcitability via increased glutamate release altering excitation/inhibition (E/I) balance in cortical networks. A recently reported SNP in prg‐1 (R345T/mutPRG‐1) affects ~5 million European and US citizens in a monoallelic variant. Our studies show that this mutation leads to a loss‐of‐PRG‐1 function at the synapse due to its inability to control lysophosphatidic acid (LPA) levels via a cellular uptake mechanism which appears to depend on proper glycosylation altered by this SNP. PRG‐1+/− mice, which are animal correlates of human PRG‐1+/mut carriers, showed an altered cortical network …
Efficacy And Safety Of Vorapaxar In Non-St-Segment Elevation Acute Coronary Syndrome Patients Undergoing Noncardiac Surgery, Sean Van Diepen, Pierluigi Tricoci, Mohua Podder, Cynthia M. Westerhout, Philip E. Aylward, Claes Held, Frans Van De Werf, John Strony, Lars Wallentin, David J. Moliterno, Harvey D. White, Kenneth W. Mahaffey, Robert A. Harrington, Paul W. Armstrong
Efficacy And Safety Of Vorapaxar In Non-St-Segment Elevation Acute Coronary Syndrome Patients Undergoing Noncardiac Surgery, Sean Van Diepen, Pierluigi Tricoci, Mohua Podder, Cynthia M. Westerhout, Philip E. Aylward, Claes Held, Frans Van De Werf, John Strony, Lars Wallentin, David J. Moliterno, Harvey D. White, Kenneth W. Mahaffey, Robert A. Harrington, Paul W. Armstrong
Gill Heart & Vascular Institute Faculty Publications
Background—Perioperative antiplatelet agents potentially increase bleeding after non–ST‐segment elevation (NSTE) acute coronary syndromes (ACS). The protease‐activated receptor 1 antagonist vorapaxar reduced cardiovascular events and was associated with increased bleeding versus placebo in NSTE ACS, but its efficacy and safety in noncardiac surgery (NCS) remain unknown. We aimed to evaluate ischemic, bleeding, and long‐term outcomes of vorapaxar in NCS after NSTE ACS.
Methods and Results—In the TRACER trial, 2202 (17.0%) patients underwent major or minor NCS after NSTE ACS over 1.5 years (median); continuing study treatment perioperatively was recommended. The primary ischemic end point for this analysis was cardiovascular …
Infusion Of Reconstituted High-Density Lipoprotein, Csl112, In Patients With Atherosclerosis: Safety And Pharmacokinetic Results From A Phase 2a Randomized Clinical Trial, Pierluigi Tricoci, Denise M. D'Andrea, Paul A. Gurbel, Zhenling Yao, Marina Cuchel, Brion Winston, Robert Schott, Robert Weiss, Michael A. Blazing, Louis Cannon, Alison L. Bailey, Dominick J. Angiolillo, Andreas Gille, Charles L. Shear, Samuel D. Wright, John H. Alexander
Infusion Of Reconstituted High-Density Lipoprotein, Csl112, In Patients With Atherosclerosis: Safety And Pharmacokinetic Results From A Phase 2a Randomized Clinical Trial, Pierluigi Tricoci, Denise M. D'Andrea, Paul A. Gurbel, Zhenling Yao, Marina Cuchel, Brion Winston, Robert Schott, Robert Weiss, Michael A. Blazing, Louis Cannon, Alison L. Bailey, Dominick J. Angiolillo, Andreas Gille, Charles L. Shear, Samuel D. Wright, John H. Alexander
Gill Heart & Vascular Institute Faculty Publications
Background CSL112 is a new formulation of human apolipoprotein A‐I (apoA‐I) being developed to reduce cardiovascular events following acute coronary syndrome. This phase 2a, randomized, double‐blind, multicenter, dose‐ranging trial represents the first clinical investigation to assess the safety and pharmacokinetics/pharmacodynamics of a CSL112 infusion among patients with stable atherosclerotic disease.
Methods and Results Patients were randomized to single ascending doses of CSL112 (1.7, 3.4, or 6.8 g) or placebo, administered over a 2‐hour period. Primary safety assessments consisted of alanine aminotransferase or aspartate aminotransferase elevations >3× upper limits of normal and study drug–related adverse events. Pharmacokinetic/pharmacodynamic assessments included apoA‐I plasma …
Lipid-Induced Epigenomic Changes In Human Macrophages Identify A Coronary Artery Disease-Associated Variant That Regulates Ppap2b Expression Through Altered C/Ebp-Beta Binding, Michael E. Reschen, Kyle J. Gaulton, Da Lin, Elizabeth J. Soilleux, Andrew J. Morris, Susan S. Smyth, Christopher A. O'Callaghan
Lipid-Induced Epigenomic Changes In Human Macrophages Identify A Coronary Artery Disease-Associated Variant That Regulates Ppap2b Expression Through Altered C/Ebp-Beta Binding, Michael E. Reschen, Kyle J. Gaulton, Da Lin, Elizabeth J. Soilleux, Andrew J. Morris, Susan S. Smyth, Christopher A. O'Callaghan
Gill Heart & Vascular Institute Faculty Publications
Genome-wide association studies (GWAS) have identified over 40 loci that affect risk of coronary artery disease (CAD) and the causal mechanisms at the majority of loci are unknown. Recent studies have suggested that many causal GWAS variants influence disease through altered transcriptional regulation in disease-relevant cell types. We explored changes in transcriptional regulation during a key pathophysiological event in CAD, the environmental lipid-induced transformation of macrophages to lipid-laden foam cells. We used a combination of open chromatin mapping with formaldehyde-assisted isolation of regulatory elements (FAIRE-seq) and enhancer and transcription factor mapping using chromatin immuno-precipitation (ChIP-seq) in primary human macrophages before …
Biomarkers Of Acute Myocardial Infarction In The Elderly: Troponin And Beyond, Martin G. Rains, Charles A. Laney, Alison L. Bailey, Charles L. Campbell
Biomarkers Of Acute Myocardial Infarction In The Elderly: Troponin And Beyond, Martin G. Rains, Charles A. Laney, Alison L. Bailey, Charles L. Campbell
Gill Heart & Vascular Institute Faculty Publications
In the broadest context, biological markers, or biomarkers, are molecules that characterize a biological system or process. In the setting of cardiovascular disease, a number of biomarkers have become an integral part of diagnostic and risk stratification strategies. In this review, we will discuss classic and emerging biomarkers of cardiovascular disease and the role of these biomarkers in the diagnosis and prognosis of elderly patients presenting with acute myocardial infarction.
Osteopontin: A Novel Regulator At The Cross Roads Of Inflammation, Obesity And Diabetes, Florian Kahles, Hannes M. Findeisen, Dennis Bruemmer
Osteopontin: A Novel Regulator At The Cross Roads Of Inflammation, Obesity And Diabetes, Florian Kahles, Hannes M. Findeisen, Dennis Bruemmer
Gill Heart & Vascular Institute Faculty Publications
Since its first description more than 20 years ago osteopontin has emerged as an active player in many physiological and pathological processes, including biomineralization, tissue remodeling and inflammation. As an extracellular matrix protein and proinflammatory cytokine osteopontin is thought to facilitate the recruitment of monocytes/macrophages and to mediate cytokine secretion in leukocytes. Modulation of immune cell response by osteopontin has been associated with various inflammatory diseases and may play a pivotal role in the development of adipose tissue inflammation and insulin resistance. Here we summarize recent findings on the role of osteopontin in metabolic disorders, particularly focusing on diabetes and …
Targeting Platelet Thrombin Receptor Signaling To Prevent Thrombosis, Eric L. Wallace, Susan S. Smyth
Targeting Platelet Thrombin Receptor Signaling To Prevent Thrombosis, Eric L. Wallace, Susan S. Smyth
Gill Heart & Vascular Institute Faculty Publications
Platelets contribute fundamentally to ischemic heart disease, and antiplatelet therapy has been critical to reducing acute thrombotic complications of atherosclerotic disease. Thrombin, by acting on protease activated receptors (PAR), is one of the most potent platelet activators. PAR-1 antagonists may therefore provide more comprehensive antithrombotic effects. We review the pathophysiology of atherothrombosis, platelet activation by thrombin, the role of platelet protease activated receptors (PAR), and the clinical data supporting their use.
Lipid Phosphate Phosphatase 3 Enables Efficient Thymic Egress, Béatrice Bréart, Willy D. Ramos-Perez, Alejandra Mendoza, Abdelghaffar K. Salous, Michael Gobert, Yong Huang, Ralf H. Adams, Juan J. Lafaille, Diana Escalante-Alcalde, Andrew J. Morris, Susan R. Schwab
Lipid Phosphate Phosphatase 3 Enables Efficient Thymic Egress, Béatrice Bréart, Willy D. Ramos-Perez, Alejandra Mendoza, Abdelghaffar K. Salous, Michael Gobert, Yong Huang, Ralf H. Adams, Juan J. Lafaille, Diana Escalante-Alcalde, Andrew J. Morris, Susan R. Schwab
Gill Heart & Vascular Institute Faculty Publications
The signaling lipid sphingosine-1-phosphate (S1P) stabilizes the vasculature, directs lymphocyte egress from lymphoid organs, and shapes inflammatory responses. However, little is known about how S1P distribution is controlled in vivo, and it is not clear how a ubiquitously made lipid functions as a signal that requires precise spatial and temporal control. We have found that lipid phosphate phosphatase 3 (LPP3) enables efficient export of mature T cells from the thymus into circulation, and several lines of evidence suggest that LPP3 promotes exit by destroying thymic S1P. Although five additional S1P-degrading enzymes are expressed in the thymus, they cannot compensate for …
Use Of Clopidogrel In The Reduction Of Myocardial Damage During Percutaneous Coronary Intervention, Arijit Dasgupta, Debabrata Mukherjee
Use Of Clopidogrel In The Reduction Of Myocardial Damage During Percutaneous Coronary Intervention, Arijit Dasgupta, Debabrata Mukherjee
Gill Heart & Vascular Institute Faculty Publications
It is estimated that approximately a quarter of patients undergoing coronary intervention may have significant post-procedural creatinine (CK)/creatinine kinase myocardial band (CK-MB) elevations and approximately half may have post-procedural troponin elevations. Current data suggest that periprocedural infarction is associated with short-, intermediate-, and long-term adverse outcomes, most notably mortality. This review examines the role of clopidogrel in decreasing periprocedural myonecrosis following percutaneous coronary intervention (PCI). Clopidogrel is an important pharmacologic agent used to reduce myocardial infarction post-coronary intervention as assessed directly by the evaluation of cardiac biomarkers and indirectly by the evaluation of short-term ischemic events. The optimal dose of …