Publications by authors named "N I Werner"

425 Publications

CAD increases the long noncoding RNA in small extracellular vesicles and regulates endothelial cell function via vesicular shuttling.

Mol Ther Nucleic Acids 2021 Sep 4;25:388-405. Epub 2021 Jun 4.

Heart Center Bonn, Molecular Cardiology, Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University of Bonn Venusberg-Campus 1, 53127 Bonn, Germany.

Long noncoding RNAs (lncRNAs) have emerged as biomarkers and regulators of cardiovascular disease. However, the expression pattern of circulating extracellular vesicle (EV)-incorporated lncRNAs in patients with coronary artery disease (CAD) is still poorly investigated. A human lncRNA array revealed that certain EV-lncRNAs are significantly dysregulated in CAD patients. Circulating small EVs (sEVs) from patients with (n = 30) or without (n = 30) CAD were used to quantify (also known as antisense RNA 1 []), , , and RNA levels. (p = 0.002) and (p = 0.02) were significantly increased in patients with CAD, compared to non-CAD patients. Fluorescent labeling and quantitative real-time PCR of sEVs demonstrated that functional was transported into the recipient cells. Mechanistically, the RNA-binding protein, heterogeneous nuclear ribonucleoprotein K (hnRNPK), interacts with , regulating its loading into sEVs. Knockdown of abrogated the EV-mediated effects on endothelial cell (EC) migration, proliferation, tube formation, and sprouting. Angiogenesis-related gene profiling showed that the expression of vascular endothelial growth factor A () RNA was significantly increased in EV recipient cells. Protein stability and RNA immunoprecipitation indicated that the -hnRNPK axis regulates the stability and binding of mRNA to hnRNPK. Loss of in EVs abolished the EV-mediated promotion of VEGFA gene and protein expression. Intercellular transfer of EV-incorporated promotes a pro-angiogenic phenotype via a VEGFA-dependent mechanism.
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http://dx.doi.org/10.1016/j.omtn.2021.05.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403722PMC
September 2021

The induction mechanism of the flavonoid-responsive regulator FrrA.

FEBS J 2021 Jul 27. Epub 2021 Jul 27.

Institute for Biochemistry, Department Molecular Structural Biology, University of Greifswald, Germany.

Bradyrhizobium diazoefficiens, a bacterial symbiont of soybean and other leguminous plants, enters a nodulation-promoting genetic programme in the presence of host-produced flavonoids and related signalling compounds. Here, we describe the crystal structure of an isoflavonoid-responsive regulator (FrrA) from Bradyrhizobium, as well as cocrystal structures with inducing and noninducing ligands (genistein and naringenin, respectively). The structures reveal a TetR-like fold whose DNA-binding domain is capable of adopting a range of orientations. A single molecule of either genistein or naringenin is asymmetrically bound in a central cavity of the FrrA homodimer, mainly via C-H contacts to the π-system of the ligands. Strikingly, however, the interaction does not provoke any conformational changes in the repressor. Both the flexible positioning of the DNA-binding domain and the absence of structural change upon ligand binding are corroborated by small-angle X-ray scattering (SAXS) experiments in solution. Together with a model of the promoter-bound state of FrrA our results suggest that inducers act as a wedge, preventing the DNA-binding domains from moving close enough together to interact with successive positions of the major groove of the palindromic operator.
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http://dx.doi.org/10.1111/febs.16141DOI Listing
July 2021

Complete Revascularisation in Impella-Supported Infarct-Related Cardiogenic Shock Patients Is Associated With Improved Mortality.

Front Cardiovasc Med 2021 9;8:678748. Epub 2021 Jul 9.

Department of Cardiology, University Heart Center, Bonn, Germany.

Acute myocardial infarction-related cardiogenic shock (AMI-CS) still has high likelihood of in-hospital mortality. The only trial evidence currently available for the intra-aortic balloon pump showed no benefit of its routine use in AMI-CS. While a potential benefit of complete revascularisation has been suggested in urgent revascularisation, the CULPRIT-SHOCK trial demonstrated no benefit of multivessel compared to culprit-lesion only revascularisation in AMI-CS. However, mechanical circulatory support was only used in a minority of patients. We hypothesised that more complete revascularisation facilitated by Impella support is related to lower mortality in AMI-CS patients. We analysed data from 202 consecutive Impella-treated AMI-CS patients at four European high-volume shock centres (age 66 ± 11 years, 83% male). Forty-seven percentage ( = 94) had cardiac arrest before Impella implantation. Revascularisation was categorised as incomplete if residual SYNTAX-score (rS) was >8. Overall 30-day mortality was 47%. Mortality was higher when Impella was implanted post-PCI (Impella-post-PCI: 57%, Impella-pre-PCI: 38%, = 0.0053) and if revascularisation was incomplete (rS ≤ 8: 37%, rS > 8: 56%, = 0.0099). Patients with both pre-PCI Impella implantation and complete revascularisation had significantly lower mortality (33%) than those with incomplete revascularisation and implantation post PCI (72%, < 0.001). Our retrospective analysis suggests that complete revascularisation supported by an Impella microaxial pump implanted prior to PCI is associated with lower mortality than incomplete revascularisation in patients with AMI-CS.
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http://dx.doi.org/10.3389/fcvm.2021.678748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299360PMC
July 2021

Feasibility of Coronary Access in Patients With Acute Coronary Syndrome and Previous TAVR.

JACC Cardiovasc Interv 2021 Jul;14(14):1578-1590

Department of Cardiology, St. Johannes Hospital, Dortmund, Germany.

Objectives: The aim of this study was to characterize the feasibility of coronary angiography (CA) and percutaneous coronary intervention (PCI) in acute settings among patients who have undergone transcatheter aortic valve replacement (TAVR).

Background: Impaired coronary access after TAVR may be challenging and particularly in acute settings could have deleterious consequences.

Methods: In this international registry, data from patients with prior TAVR requiring urgent or emergent CA were retrospectively collected. A total of 449 patients from 25 sites with acute coronary syndromes (89.1%) and other acute cardiovascular situations (10.9%) were included.

Results: Success rates were high for CA of the right coronary artery (98.3%) and left coronary artery (99.3%) and were higher among patients with short stent-frame prostheses (SFPs) than in those with long SFPs for CA of the right coronary artery (99.6% vs 95.9%; P = 0.005) but not for CA of the left coronary artery (99.7% vs 98.7%; P = 0.24). PCI of native coronary arteries was successful in 91.4% of cases and independent of valve type (short SFP 90.4% vs long SFP 93.4%; P = 0.44). Guide engagement failed in 6 patients, of whom 3 underwent emergent coronary artery bypass grafting and another 3 died in the hospital. Among patients requiring revascularization of native vessels, independent predictors of 30-day all-cause mortality were prior diabetes, cardiogenic shock, and failed PCI but not valve type or success of coronary engagement.

Conclusions: CA or PCI after TAVR in acute settings is usually successful, but selective coronary engagement may be more challenging in the presence of long SFPs. Among patients requiring PCI, prior diabetes, cardiogenic shock, and failed PCI were predictors of early mortality.
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http://dx.doi.org/10.1016/j.jcin.2021.05.007DOI Listing
July 2021

Pelvic Fracture-Related Hypotension: A Review of Contemporary Adjuncts for Hemorrhage Control.

J Trauma Acute Care Surg 2021 Jul 6. Epub 2021 Jul 6.

R Adams Cowley Shock Trauma Center, University of Maryland Medical System Department of Surgery, Denver Health Medical Center, Denver, CO. Division of Trauma, Critical Care, Emergency Surgery, and Burns, Department of Surgery, College of Medicine, University of Arizona, Tucson, AZ Baylor University Medical Center in Dallas University of Utah, Department of Orthopaedic Surgery, Salt Lake City, Utah Division of Trauma and Surgical Critical Care, LAC+USC Medical Center, University of Southern California, Los Angeles, California Trauma/Surgical Critical Care at Grady Memorial Hospital / Emory University School of Medicine Division of Trauma, Surgical Critical Care, Burns and Acute Care Surgery, Department of Surgery, University of California San Diego School of Medicine.

Major pelvic hemorrhage remains a considerable challenge of modern trauma care associated with mortality in over a third of patients. Efforts to improve outcomes demand continued research into the optimal employment of both traditional and newer hemostatic adjuncts across the full spectrum of emergent care environments. The purpose of this review is to provide a concise description of the rationale for and effective use of currently available adjuncts for the control of pelvic hemorrhage. Additionally, the challenges of defining the optimal order and algorithm for employment of these adjuncts will be outlined.

Level Of Evidence: IV.
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http://dx.doi.org/10.1097/TA.0000000000003331DOI Listing
July 2021
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