Tanja K. Rudolph

Bio: Tanja K. Rudolph is an academic researcher from Ruhr University Bochum. The author has contributed to research in topics: Medicine & Cardiology. The author has an hindex of 35, co-authored 118 publications receiving 3780 citations. Previous affiliations of Tanja K. Rudolph include University of Hamburg & University of Cologne.

Cyclooxygenase-2 generates anti-inflammatory mediators from omega-3 fatty acids

Abstract: Electrophilic fatty acids are generated during inflammation by non-enzymatic reactions and can modulate inflammatory responses. We used a new mass spectrometry-based electrophile capture strategy to reveal the formation of electrophilic oxo-derivatives (EFOX) from the omega-3 fatty acids docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA). These EFOX were generated by a cyclooxygenase-2 (COX-2)-catalyzed mechanism in activated macrophages. Modulation of COX-2 activity by aspirin increased the rate of EFOX production and their intracellular levels. Owing to their electrophilic nature, EFOX adducted to cysteine and histidine residues of proteins and activated Nrf2-dependent anti-oxidant gene expression. We confirmed the anti-inflammatory nature of DHA- and DPA-derived EFOX by showing that they can act as peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonists and inhibit pro-inflammatory cytokine and nitric oxide production, all within biological concentration ranges. These data support the idea that EFOX are signaling mediators that transduce the beneficial clinical effects of omega-3 fatty acids, COX-2 and aspirin.

Myeloperoxidase acts as a profibrotic mediator of atrial fibrillation.

Abstract: Observational clinical and ex vivo studies have established a strong association between atrial fibrillation and inflammation1. However, whether inflammation is the cause or the consequence of atrial fibrillation and which specific inflammatory mediators may increase the atria's susceptibility to fibrillation remain elusive. Here we provide experimental and clinical evidence for the mechanistic involvement of myeloperoxidase (MPO), a heme enzyme abundantly expressed by neutrophils, in the pathophysiology of atrial fibrillation. MPO-deficient mice pretreated with angiotensin II (AngII) to provoke leukocyte activation showed lower atrial tissue abundance of the MPO product 3-chlorotyrosine, reduced activity of matrix metalloproteinases and blunted atrial fibrosis as compared to wild-type mice. Upon right atrial electrophysiological stimulation, MPO-deficient mice were protected from atrial fibrillation, which was reversed when MPO was restored. Humans with atrial fibrillation had higher plasma concentrations of MPO and a larger MPO burden in right atrial tissue as compared to individuals devoid of atrial fibrillation. In the atria, MPO colocalized with markedly increased formation of 3-chlorotyrosine. Our data demonstrate that MPO is a crucial prerequisite for structural remodeling of the myocardium, leading to an increased vulnerability to atrial fibrillation.

Transduction of Redox Signaling by Electrophile-Protein Reactions

Abstract: Chemically reactive by-products of cellular redox reactions are frequently thought to induce deleterious actions. However, not all redox-mediated modifications are harmful; some have important physiological consequences. Some posttranslational protein modifications that are induced by electrophilic products of redox reactions may modulate physiological signaling pathways that have evolved to act as sensors of oxidative conditions. Additional insight into specific biological targets of electrophiles and the regulation of their reactions can reveal new therapeutic strategies for treating pain, acute and chronic inflammatory injury, and metabolic diseases. This Review with 4 figures, 2 tables, and 148 references describes biologically important electrophiles, methods for detecting proteins modified by these electrophilic compounds and the cellular consequences of this type of posttranslational modification.

Endogenous generation and protective effects of nitro-fatty acids in a murine model of focal cardiac ischaemia and reperfusion.

Abstract: Aims Nitrated fatty acids (NO2-FA) have been identified as endogenous anti-inflammatory signalling mediators generated by oxidative inflammatory reactions. Herein the in vivo generation of nitro-oleic acid (OA-NO2) and nitro-linoleic acid (LNO2) was measured in a murine model of myocardial ischaemia and reperfusion (I/R) and the effect of exogenous administration of OA-NO2 on I/R injury was evaluated. Methods and results In C57/BL6 mice subjected to 30 min of coronary artery ligation, endogenous OA-NO2 and LNO2 formation was observed after 30 min of reperfusion, whereas no NO2-FA were detected in sham-operated mice and mice with myocardial infarction without reperfusion. Exogenous administration of 20 nmol/g body weight OA-NO2 during the ischaemic episode induced profound protection against I/R injury with a 46% reduction in infarct size (normalized to area at risk) and a marked preservation of left ventricular function as assessed by transthoracic echocardiography, compared with vehicle-treated mice. Administration of OA-NO2 inhibited activation of the p65 subunit of nuclear factor κB (NFκB) in I/R tissue. Experiments using the NFκB inhibitor pyrrolidinedithiocarbamate also support that protection lent by OA-NO2 was in part mediated by inhibition of NFκB. OA-NO2 inhibition of NFκB activation was accompanied by suppression of downstream intercellular adhesion molecule 1 and monocyte chemotactic protein 1 expression, neutrophil infiltration, and myocyte apoptosis. Conclusion This study reveals the de novo generation of fatty acid nitration products in vivo and reveals the anti-inflammatory and potential therapeutic actions of OA-NO2 in myocardial I/R injury.

Heparins Increase Endothelial Nitric Oxide Bioavailability by Liberating Vessel-Immobilized Myeloperoxidase

Abstract: Background— Neutrophils and monocytes are centrally linked to vascular inflammatory disease, and leukocyte-derived myeloperoxidase (MPO) has emerged as an important mechanistic participant in impaired vasomotor function. MPO binds to and transcytoses endothelial cells in a glycosaminoglycan-dependent manner, and MPO binding to the vessel wall is a prerequisite for MPO-dependent oxidation of endothelium-derived nitric oxide (NO) and impairment of endothelial function in animal models. In the present study, we investigated whether heparin mobilizes MPO from vascular compartments in humans and defined whether this translates into increased vascular NO bioavailability and function. Methods and Results— Plasma MPO levels before and after heparin administration were assessed by ELISA in 109 patients undergoing coronary angiography. Whereas baseline plasma MPO levels did not differ between patients with or without angiographically detectable coronary artery disease (CAD), the increase in MPO plasma content on bo...

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society

Abstract: Jeffrey L. Anderson, MD, FACC, FAHA, Chair Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect Nancy M. Albert, PhD, RN, FAHA Biykem Bozkurt, MD, PhD, FACC, FAHA Ralph G. Brindis, MD, MPH, MACC Mark A. Creager, MD, FACC, FAHA[#][1] Lesley H. Curtis, PhD, FAHA David DeMets, PhD[#][1] Robert A

2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).

Abstract: ALAT : alanine aminotransferase ASAT : aspartate aminotransferase APAH : associated pulmonary arterial hypertension BAS : balloon atrial septostomy BMPR2 : bone morphogenetic protein receptor 2 BNP : brain natriuretic peptide BPA : balloon pulmonary angioplasty BREATHE : Bosentan

Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association.

Abstract: Each chapter listed in the Table of Contents (see next page) is a hyperlink to that chapter. The reader clicks the chapter name to access that chapter. Each chapter listed here is a hyperlink. Click on the chapter name to be taken to that chapter. Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together in a single document the most up-to-date statistics related to heart disease, stroke, and the cardiovascular risk factors listed in the AHA’s My Life Check - Life’s Simple 7 (Figure1), which include core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure [BP], and glucose control) that contribute to cardiovascular health. The Statistical Update represents …

Special article2015 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension

Abstract: Published on behalf of the European Society of Cardiology. All rights reserved. & 2015 European Society of Cardiology & European Respiratory Society. This article is being published concurrently in the European Heart Journal (10.1093/eurheartj/ehv317) and the European Respiratory Journal (10.1183/13993003.01032-2015). The articles are identical except for minor stylistic and spelling differences in keeping with each journal’s style. Either citation can be used when citing this article. * Corresponding authors: Nazzareno Galiè, Department of Experimental, Diagnostic and Specialty Medicine–DIMES, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy, Tel: +39 051 349 858, Fax: +39 051 344 859, Email: nazzareno.galie@unibo.it.

[2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension].

Abstract: Nazzareno Galiè (ESC Chairperson), Marc Humbert (ERS Chairperson), Jean-Luc Vachiery, Simon Gibbs, Irene Lang, Adam Torbicki, Gérald Simonneau, Andrew Peacock, Anton Vonk Noordegraaf, Maurice Beghetti, Ardeschir Ghofrani, Miguel Angel Gomez Sanchez, Georg Hansmann, Walter Klepetko, Patrizio Lancellotti, Marco Matucci, Theresa McDonagh, Luc A. Pierard, Pedro T. Trindade, Maurizio Zompatori and Marius Hoeper The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and of the European Respiratory Society (ERS)