12 results on '"Sager, Hendrik B."'
Search Results
2. Coronary no-reflow and adverse events in patients with acute myocardial infarction after percutaneous coronary intervention with current drug-eluting stents and third-generation P2Y12 inhibitors.
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Ndrepepa, Gjin, Cassese, Salvatore, Xhepa, Erion, Joner, Michael, Sager, Hendrik B., Kufner, Sebastian, Laugwitz, Karl-Ludwig, Schunkert, Heribert, and Kastrati, Adnan
- Abstract
Background: The frequency and prognostic value of coronary no-reflow (CNR) was investigated in studies that have used an outdated reperfusion therapy in terms of stent technology and antithrombotic drugs. We assessed the association of CNR with adverse outcomes in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and newer antithrombotic drugs, ticagrelor or prasugrel. Methods: This study included 3100 patients with AMI who underwent PCI with current DES and third-generation P2Y
12 inhibitors. CNR was defined as Thrombolysis in Myocardial Infarction (TIMI) blood flow grade ≤ 2 at the end of PCI. The primary end point was 1-year incidence of net adverse clinical and cerebral events—a composite end point of death of any cause, myocardial infarction, stroke or major bleeding. Results: CNR was diagnosed in 130 patients (4.2%). The primary end point occurred in 28 patients in the CNR group and 354 patients in the reflow group (cumulative incidence 23.2% and 12.8%; adjusted hazard ratio = 1.53, 95% confidence interval 1.01–2.33; P = 0.049). The 1-year incidences of death or myocardial infarction (14.6% vs. 7.6%; P = 0.003), myocardial infarction (8.8% vs. 3.9%; P = 0.007) and major bleeding (10.9% vs. 5.6%; P = 0.008) were significantly higher in patients with CNR than patients with reflow. The risk of adverse events in patients with CNR was highest within the first 30 days after PCI. Conclusion: In patients with AMI undergoing PCI with current DES and third generation P2Y12 receptor inhibitors, CNR was associated with a higher risk of adverse outcomes at 1 year. [ABSTRACT FROM AUTHOR]- Published
- 2024
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3. Modified balloons to prepare severely calcified coronary lesions before stent implantation: a systematic review and meta-analysis of randomized trials.
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Scalamogna, Maria, Kuna, Constantin, Voll, Felix, Aytekin, Alp, Lahu, Shqipdona, Kessler, Thorsten, Kufner, Sebastian, Rheude, Tobias, Sager, Hendrik B., Xhepa, Erion, Wiebe, Jens, Joner, Michael, Ndrepepa, Gjin, Kastrati, Adnan, and Cassese, Salvatore
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Background: The performance of modified balloons (namely cutting or scoring balloons) to prepare severely calcified lesions in patients undergoing percutaneous coronary intervention (PCI) remains controversial. We investigated the clinical and imaging outcomes of patients undergoing PCI assigned to modified balloon therapy to prepare severely calcified coronary lesions before stent implantation. Methods: In this meta-analysis, we aggregated the study-level data from trials enrolling invasively treated patients who were randomly assigned to modified balloon or control therapy to prepare severely calcified lesions before stenting. The primary outcome was major adverse cardiac events (MACE), including death, myocardial infarction (MI), and repeat revascularization. The secondary outcomes included the individual components of the primary outcome, coronary perforation and final minimal stent area (MSA) as measured by intracoronary imaging. Results: A total of 648 participants in six trials were allocated to modified balloon therapy (n = 335) or control therapy (semi-compliant, non-compliant, or super high-pressure balloon, n = 313). The median follow-up was 11 months. Overall, MACE occurred in 8.96% of patients assigned to a modified balloon and 12.78% of patients assigned to control therapy [risk ratio = 0.70, 95% confidence interval (CI) 0.35–1.39; P = 0.24]. There was a significant treatment effect-by-modified balloon type interaction for the outcome MACE in patients assigned to cutting balloon compared with control therapy [RR = 0.40 (0.28–0.56), P for interaction (P
int ) < 0.001]. Patients treated with a modified balloon compared with control therapy showed neither a significant difference for the other clinical outcomes nor for final MSA [standardized mean difference = 0.67 (− 0.71, 2.06); P = 0.26]. Conclusions: In patients treated with PCI for severely calcific coronary artery disease a strategy of lesion preparation with a modified balloon before stenting does not improve clinical or imaging outcomes compared with control therapy. The different performance of cutting and scoring balloons warrants further investigation. [ABSTRACT FROM AUTHOR]- Published
- 2024
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4. Clinician Scientists in der kardiovaskulären Medizin: Positionspapier der Deutschen Gesellschaft für Kardiologie.
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Hilgendorf, Ingo, Backs, Johannes, Baldus, Stephan, Chen, Jessy, Duncker, David, El-Armouche, Ali, Frey, Norbert, Hilfiker-Kleiner, Denise, Johnson, Victoria, Künzel, Stephan, Wollert, Kai C., Zeiher, Andreas, and Sager, Hendrik B.
- Abstract
Copyright of Die Kardiologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2023
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5. Functional investigation of the coronary artery disease gene SVEP1.
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Winkler, Michael J., Müller, Philipp, Sharifi, Amin M., Wobst, Jana, Winter, Hanna, Mokry, Michal, Ma, Lijiang, van der Laan, Sander W., Pang, Shichao, Miritsch, Benedikt, Hinterdobler, Julia, Werner, Julia, Stiller, Barbara, Güldener, Ulrich, Webb, Tom R., Asselbergs, Folkert W., Björkegren, Johan L. M., Maegdefessel, Lars, Schunkert, Heribert, and Sager, Hendrik B.
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A missense variant of the sushi, von Willebrand factor type A, EGF and pentraxin domain containing protein 1 (SVEP1) is genome-wide significantly associated with coronary artery disease. The mechanisms how SVEP1 impacts atherosclerosis are not known. We found endothelial cells (EC) and vascular smooth muscle cells to represent the major cellular source of SVEP1 in plaques. Plaques were larger in atherosclerosis-prone Svep1 haploinsufficient (ApoE
−/− Svep1+/− ) compared to Svep1 wild-type mice (ApoE−/− Svep1+/+ ) and ApoE−/− Svep1+/− mice displayed elevated plaque neutrophil, Ly6Chigh monocyte, and macrophage numbers. We assessed how leukocytes accumulated more inside plaques in ApoE−/− Svep1+/− mice and found enhanced leukocyte recruitment from blood into plaques. In vitro, we examined how SVEP1 deficiency promotes leukocyte recruitment and found elevated expression of the leukocyte attractant chemokine (C-X-C motif) ligand 1 (CXCL1) in EC after incubation with missense compared to wild-type SVEP1. Increasing wild-type SVEP1 levels silenced endothelial CXCL1 release. In line, plasma Cxcl1 levels were elevated in ApoE−/− Svep1+/− mice. Our studies reveal an atheroprotective role of SVEP1. Deficiency of wild-type Svep1 increased endothelial CXCL1 expression leading to enhanced recruitment of proinflammatory leukocytes from blood to plaque. Consequently, elevated vascular inflammation resulted in enhanced plaque progression in Svep1 deficiency. [ABSTRACT FROM AUTHOR]- Published
- 2020
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6. Serum microRNA-1233 is a specific biomarker for diagnosing acute pulmonary embolism
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Kessler, Thorsten, Erdmann, Jeanette, Vilne, Baiba, Bruse, Petra, Kurowski, Volkhard, Diemert, Patrick, Schunkert, Heribert, and Sager, Hendrik B.
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ddc - Published
- 2015
7. Stimulators of the soluble guanylyl cyclase: promising functional insights from rare coding atherosclerosis-related GUCY1A3 variants.
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Wobst, Jana, von Ameln, Simon, Wolf, Bernhard, Wierer, Michael, An Dang, Tan, Sager, Hendrik B., Tennstedt, Stephanie, Hengstenberg, Christian, Koesling, Doris, Friebe, Andreas, Braun, Siegmund L., Erdmann, Jeanette, Schunkert, Heribert, and Kessler, Thorsten
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Stimulators of the soluble guanylyl cyclase (sGC) are emerging therapeutic agents in cardiovascular diseases. Genetic alterations of the GUCY1A3 gene, which encodes the α
1 subunit of the sGC, are associated with coronary artery disease. Studies investigating sGC stimulators in subjects with CAD and carrying risk-related variants in sGC are, however, lacking. Here, we functionally investigate the impact of coding GUCY1A3 variants on sGC activity and the therapeutic potential of sGC stimulators in vitro. In addition to a known loss-of-function variant, eight coding variants in GUCY1A3 were cloned and expressed in HEK 293 cells. Protein levels and dimerization capability with the β1 subunit were analysed by immunoblotting and co-immunoprecipitation, respectively. All α1 variants found in MI patients dimerized with the β1 subunit. Protein levels were reduced by 72% in one variant (p<0.01). Enzymatic activity was analysed using cGMP radioimmunoassay after stimulation with a nitric oxide (NO) donor. Five variants displayed decreased cGMP production upon NO stimulation (p<0.001). The addition of the sGC stimulator BAY 41-2272 increased cGMP formation in all of these variants (p<0.01). Except for the variant leading to decreased protein level, cGMP amounts reached the wildtype NO-induced level after addition of BAY 41-2272. In conclusion, rare coding variants in GUCY1A3 lead to reduced cGMP formation which can be rescued by a sGC stimulator in vitro. These results might therefore represent the starting point for discovery of novel treatment strategies for patients at risk with coding GUCY1A3 variants. [ABSTRACT FROM AUTHOR]- Published
- 2016
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8. In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight.
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Dahlman, James E., Barnes, Carmen, Khan, Omar F., Thiriot, Aude, Jhunjunwala, Siddharth, Shaw, Taylor E., Xing, Yiping, Sager, Hendrik B., Sahay, Gaurav, Speciner, Lauren, Bader, Andrew, Bogorad, Roman L., Yin, Hao, Racie, Tim, Dong, Yizhou, Jiang, Shan, Seedorf, Danielle, Dave, Apeksha, Singh Sandhu, Kamaljeet, and Webber, Matthew J.
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SMALL interfering RNA ,ENDOTHELIAL cells ,NANOPARTICLES ,MOLECULAR weights ,GENE expression - Abstract
Dysfunctional endothelium contributes to more diseases than any other tissue in the body. Small interfering RNAs (siRNAs) can help in the study and treatment of endothelial cells in vivo by durably silencing multiple genes simultaneously, but efficient siRNA delivery has so far remained challenging. Here, we show that polymeric nanoparticles made of low-molecular-weight polyamines and lipids can deliver siRNA to endothelial cells with high efficiency, thereby facilitating the simultaneous silencing of multiple endothelial genes in vivo. Unlike lipid or lipid-like nanoparticles, this formulation does not significantly reduce gene expression in hepatocytes or immune cells even at the dosage necessary for endothelial gene silencing. These nanoparticles mediate the most durable non-liver silencing reported so far and facilitate the delivery of siRNAs that modify endothelial function in mouse models of vascular permeability, emphysema, primary tumour growth and metastasis. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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9. Chronic variable stress activates hematopoietic stem cells.
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Heidt, Timo, Sager, Hendrik B, Courties, Gabriel, Dutta, Partha, Iwamoto, Yoshiko, Zaltsman, Alex, von zur Muhlen, Constantin, Bode, Christoph, Fricchione, Gregory L, Denninger, John, Lin, Charles P, Vinegoni, Claudio, Libby, Peter, Swirski, Filip K, Weissleder, Ralph, and Nahrendorf, Matthias
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PSYCHOLOGICAL stress , *HEMATOPOIETIC stem cells , *CATECHOLAMINES , *IMMUNE system , *MYOCARDIAL infarction , *ATHEROSCLEROSIS - Abstract
Exposure to psychosocial stress is a risk factor for many diseases, including atherosclerosis. Although incompletely understood, interaction between the psyche and the immune system provides one potential mechanism linking stress and disease inception and progression. Known cross-talk between the brain and immune system includes the hypothalamic-pituitary-adrenal axis, which centrally drives glucocorticoid production in the adrenal cortex, and the sympathetic-adrenal-medullary axis, which controls stress-induced catecholamine release in support of the fight-or-flight reflex. It remains unknown, however, whether chronic stress changes hematopoietic stem cell activity. Here we show that stress increases proliferation of these most primitive hematopoietic progenitors, giving rise to higher levels of disease-promoting inflammatory leukocytes. We found that chronic stress induced monocytosis and neutrophilia in humans. While investigating the source of leukocytosis in mice, we discovered that stress activates upstream hematopoietic stem cells. Under conditions of chronic variable stress in mice, sympathetic nerve fibers released surplus noradrenaline, which signaled bone marrow niche cells to decrease CXCL12 levels through the β3-adrenergic receptor. Consequently, hematopoietic stem cell proliferation was elevated, leading to an increased output of neutrophils and inflammatory monocytes. When atherosclerosis-prone Apoe−/− mice were subjected to chronic stress, accelerated hematopoiesis promoted plaque features associated with vulnerable lesions that cause myocardial infarction and stroke in humans. [ABSTRACT FROM AUTHOR]
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- 2014
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10. Lethal hemorrhage caused by aortoesophageal fistula secondary to stent-graft repair of the thoracic aorta.
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Sager, Hendrik, Wellhöner, Peter, Wermelt, Johanna, Schunkert, Heribert, Kurowski, Volkhard, Sager, Hendrik B, Wellhöner, Peter, and Wermelt, Johanna A
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Aortoesophageal fistula (AEF) is a rare but life-threatening complication after endovascular or surgical aortic repair. Here we report a patient with AEF secondary to aortic stent-placement 2 years earlier who presented with hematemesis and died from hemorrhagic shock. By means of this case and the literature, we highlight potential bleeding sources in such a scenario because this is of crucial importance for the management strategy. [ABSTRACT FROM AUTHOR]
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- 2011
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11. Targeting mannose receptor expression on macrophages in atherosclerotic plaques of apolipoprotein E-knockout mice using 68Ga-NOTA-anti-MMR nanobody: non-invasive imaging of atherosclerotic plaques.
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Varasteh, Zohreh, Mohanta, Sarajo, Li, Yuanfang, López Armbruster, Nicolás, Braeuer, Miriam, Nekolla, Stephan G., Habenicht, Andreas, Sager, Hendrik B., Raes, Geert, Weber, Wolfgang, Hernot, Sophie, and Schwaiger, Markus
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MANNOSE ,MACROPHAGES ,ATHEROSCLEROTIC plaque ,APOLIPOPROTEIN E ,RADIOCHEMICAL purification - Abstract
Background: Rupture-prone atherosclerotic plaques are characterized by heavy macrophage infiltration, and the presence of certain macrophage subsets might be a sign for plaque vulnerability. The mannose receptor (MR, CD206) is over-expressed in several types of alternatively activated macrophages. In this study, our objective was to evaluate the feasibility of a Gallium-68 (
68 Ga)-labelled anti-MR nanobody (68 Ga-anti-MMR Nb) for the visualization of MR-positive (MR+ ) macrophages in atherosclerotic plaques of apolipoprotein E-knockout (ApoE-KO) mice.Results: NOTA-anti-MMR Nb was labelled with68 Ga with radiochemical purity > 95%. In vitro cell-binding studies demonstrated selective and specific binding of the tracer to M2a macrophages. For in vivo atherosclerotic plaque imaging studies,68 Ga-NOTA-anti-MMR Nb was injected into ApoE-KO and control mice intravenously (i.v.) and scanned 1 h post-injection for 30 min using a dedicated animal PET/CT. Focal signals could be detected in aortic tissue of ApoE-KO mice, whereas no signal was detected in the aortas of control mice.68 Ga-NOTA-anti-MMR Nb uptake was detected in atherosclerotic plaques on autoradiographs and correlated well with Sudan-IV-positive areas. The calculated ratio of plaque-to-normal aortic tissue autoradiographic signal intensity was 7.7 ± 2.6 in aortas excised from ApoE-KO mice. Immunofluorescence analysis of aorta cross-sections confirmed predominant MR expression in macrophages located in the fibrous cap layer and shoulder region of the plaques.Conclusions:68 Ga-NOTA-anti-MMR Nb allows non-invasive PET/CT imaging of MR expression in atherosclerotic lesions in a murine model and may represent a promising tool for clinical imaging and evaluation of plaque (in)stability. [ABSTRACT FROM AUTHOR]- Published
- 2019
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12. Loss of soluble guanylyl cyclase in platelets contributes to atherosclerotic plaque formation and vascular inflammation.
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Mauersberger C, Sager HB, Wobst J, Dang TA, Lambrecht L, Koplev S, Stroth M, Bettaga N, Schlossmann J, Wunder F, Friebe A, Björkegren JLM, Dietz L, Maas SL, van der Vorst EPC, Sandner P, Soehnlein O, Schunkert H, and Kessler T
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Variants in genes encoding the soluble guanylyl cyclase (sGC) in platelets are associated with coronary artery disease (CAD) risk. Here, by using histology, flow cytometry and intravital microscopy, we show that functional loss of sGC in platelets of atherosclerosis-prone Ldlr
-/- mice contributes to atherosclerotic plaque formation, particularly via increasing in vivo leukocyte adhesion to atherosclerotic lesions. In vitro experiments revealed that supernatant from activated platelets lacking sGC promotes leukocyte adhesion to endothelial cells (ECs) by activating ECs. Profiling of platelet-released cytokines indicated that reduced platelet angiopoietin-1 release by sGC-depleted platelets, which was validated in isolated human platelets from carriers of GUCY1A1 risk alleles, enhances leukocyte adhesion to ECs. I mp or ta ntly, p ha rm ac ol ogical sGC stimulation increased platelet angiopoietin-1 release in vitro and reduced leukocyte recruitment and atherosclerotic plaque formation in atherosclerosis-prone Ldlr-/- mice. Therefore, pharmacological sGC stimulation might represent a potential therapeutic strategy to prevent and treat CAD., Competing Interests: Competing interests H.S. has received personal fees from MSD Sharp & Dohme, Amgen, Bayer Vital GmbH, Boehringer Ingelheim, Daiichi Sankyo, Novartis, Servier, Brahms, Bristol Myers Squibb, Medtronic, Sanofi Aventis, Synlab, Pfizer and Vifor T as well as grants and personal fees from AstraZeneca that are unrelated to the submitted work. H.S. and T.K. are named inventors on a patent application for the prevention of restenosis after angioplasty and stent implantation (patent applicants: Klinikum rechts der Isar, German Heart Centre Munich; inventors: T. Kessler, A. Kastrati, H. Schunkert; application no. PCT/EP2021/053116; status: pending), which is unrelated to the submitted work. T.K. received lecture fees from Bayer HealthCare Pharmaceuticals. L.D., F.W. and P.S. are full-time employees of Bayer HealthCare Pharmaceuticals. The other authors declare no competing interests.- Published
- 2022
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