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Coronary Artery Disease: HELP
Articles by Georg Nickenig
Based on 18 articles published since 2008
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Between 2008 and 2019, G. Nickenig wrote the following 18 articles about Coronary Artery Disease.
 
+ Citations + Abstracts
1 Guideline [The heart team in planning and performance of revascularization : ESC guidelines versus clinical routine]. 2016

Sinning, J-M / Welz, A / Nickenig, G. ·Medizinische Klinik und Poliklinik II, Herzzentrum der Universität Bonn, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Deutschland. jan-malte.sinning@ukb.uni-bonn.de. · Klinik für Herzchirurgie, Herzzentrum der Universität Bonn, Universitätsklinikum Bonn, Bonn, Deutschland. · Medizinische Klinik und Poliklinik II, Herzzentrum der Universität Bonn, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Deutschland. ·Herz · Pubmed #27596003.

ABSTRACT: The heart team, consisting of conservative cardiologists, cardiac surgeons and interventional cardiologists, is important for a balanced, multidisciplinary decision-making process for patients suffering from coronary artery disease (CAD). Standard evidence-based, interdisciplinary, institutional protocols can be used for commonly encountered case scenarios to avoid the need for a systematic case by case review. Complex cases with a SYNTAX score of more than 32, diabetes mellitus and lesions of the left main stem or three-vessel disease should in general not be treated by an ad hoc percutaneous coronary intervention (PCI) but first discussed in the heart team. Culprit lesion PCI is usually the first choice in most patients with acute coronary syndrome. If complete percutaneous revascularization is not possible, coronary artery bypass grafting (CABG) should be considered by the heart team. In patients assigned for CABG, timing of the procedure should be decided on an individual basis, depending on the symptoms, hemodynamic stability, coronary anatomy and signs of ischemia. In stabilized patients with acute coronary syndrome, the choice of revascularization modality can be made in analogy to patients with stable CAD.

2 Editorial Response to drug-eluting stents do we need drugs to recompense drug elution? 2009

Nickenig, Georg / Sinning, Jan-Malte. · ·J Am Coll Cardiol · Pubmed #19958970.

ABSTRACT: -- No abstract --

3 Review Complex PCI procedures: challenges for the interventional cardiologist. 2018

Werner, Nikos / Nickenig, Georg / Sinning, Jan-Malte. ·Medizinische Klinik und Poliklinik II, Herzzentrum Bonn, Universitätsklinikum Bonn, 53105, Bonn, Germany. nikos.werner@ukbonn.de. · Medizinische Klinik und Poliklinik II, Herzzentrum Bonn, Universitätsklinikum Bonn, 53105, Bonn, Germany. ·Clin Res Cardiol · Pubmed #29978353.

ABSTRACT: In recent years, the percentage of patients with multivessel disease and multiple complex stenoses have significantly increased. One factor contributing to this increase is the proportion of elderly and very elderly patients who have been turned down by the Heart Team for surgical revascularization (Landes et al. in Catheter Cardiovasc Interv, https://doi.org/10.1002/ccd.27375 , 2017; Waldo et al. in Circulation 130:2295-2301, https://doi.org/10.1161/CIRCULATIONAHA.114.011541 , 2014). In addition, the marked increase in patients with significant comorbidities further contributes to the increase in patients referred to the interventional cardiologist for stenting procedures. Mostly, the complexity of these patients is characterized not only by their comorbidities but also by multivessel disease, bifurcation disease, left main disease, or stenoses of calcified or tortuous vessels, degenerated saphenous vein graft lesions, and thrombotic lesions (Kirtane et al. in Circulation 134:422-431, 2016; Gennaro Giustino et al. in JACC 86:1851-1864, 2016) These specific lesion types are typically associated with lower rates of procedural success and higher rates of recurrence or major adverse cardiac events (Kirtane et al. 2016) Coming along with this problem, virtually no study exists evaluating revascularization strategies, i.e. percutaneous coronary intervention (PCI), coronary artery bypass graft surgery, or medical therapy alone in complex patients with complex coronary anatomy. Therefore, we are confronted with an increasing patient population that is understudied and potentially underserved. In the absence of robust, accurate, objective, and consistent evidence which could help us in decision-making (e.g. best revascularization strategy, complication prevention, post-interventional medical therapy), we have to stick to personal experience and patients' preferences. In this article, we provide an overview about common definition of complex PCI, general strategies to help decision-making in these patients, and give an overview about post-interventional medical treatment.

4 Clinical Trial A novel paclitaxel-eluting stent with an ultrathin abluminal biodegradable polymer 9-month outcomes with the JACTAX HD stent. 2010

Grube, Eberhard / Schofer, Joachim / Hauptmann, Karl E / Nickenig, Georg / Curzen, Nicholas / Allocco, Dominic J / Dawkins, Keith D. ·HELIOS Heart Center, Siegburg, Germany. GrubeE@aol.com ·JACC Cardiovasc Interv · Pubmed #20398872.

ABSTRACT: OBJECTIVES: The JACTAX HD trial ("JACTAX" Trial Drug Eluting Stent Trial) evaluated the safety and clinical performance of a novel JACTAX HD (Boston Scientific Corporation, Natick, Massachusetts) paclitaxel-eluting stent (PES) in de novo coronary lesions. BACKGROUND: The JACTAX HD (Boston Scientific) stent consists of a pre-crimped bare-metal Liberté (Boston Scientific) stent coated on its abluminal aspect with an ultrathin (<1 microm) 1/1 mixture of biodegradable polylactide polymer and paclitaxel applied as discrete microdots (nominal totals of 9.2 microg each of polymer and paclitaxel per 16-mm stent). METHODS: In this prospective, single-arm, multicenter, first-human-use study (n = 103), the primary end point of 9-month major adverse cardiac events (MACE) (cardiac death, myocardial infarction, ischemia-related target vessel revascularization) was compared with an objective performance criterion (OPC) of 17% (11% MACE based on TAXUS ATLAS [TAXUS Liberté-SR Stent for the Treatment of de Novo Coronary Artery Lesions] trial results plus a pre-specified noninferiority margin of 6%). RESULTS: The composite primary end point occurred in 7.8% of JACTAX HD patients with an upper 1-sided 95% confidence limit of 13.6%, thus meeting the pre-specified criteria for noninferiority. There was no death, Q-wave myocardial infarction, or stent thrombosis through 9 months. In-stent late loss was 0.33 +/- 0.45 mm, with an in-stent binary restenosis of 5.2% and net volume obstruction by intravascular ultrasound of 11.4 +/- 11.2%. CONCLUSIONS: The JACTAX HD stent with an abluminal biodegradable polymer showed 9-month MACE, in-stent late loss, restenosis, and net volume obstruction comparable to that observed with the TAXUS Liberté (Boston Scientific) stent coated with a conformal durable polymer. Further studies are underway to better evaluate the potential of this new PES design, which might allow for more rapid endothelialization and improved vessel healing. ("JACTAX" Trial Drug Eluting Stent Trial; NCT00754728).

5 Article Impact of coronary artery disease in patients undergoing transfemoral transcatheter aortic valve implantation. 2017

Shamekhi, Jasmin / Stundl, Anja / Weber, Marcel / Mellert, Fritz / Welz, Armin / Grube, Eberhard / Nickenig, Georg / Werner, Nikos / Sinning, Jan-Malte. ·Heart Center, Department of Medicine II, University Hospital Bonn, Bonn, Germany. · Heart Center, Department of Cardiac Surgery, University Hospital Bonn, Bonn, Germany. · Heart Center, Department of Medicine II, University Hospital Bonn, Bonn, Germany. Electronic address: jan-malte.sinning@ukb.uni-bonn.de. ·Int J Cardiol · Pubmed #28789844.

ABSTRACT: BACKGROUND: The impact of coronary artery disease (CAD) and revascularization on outcome in patients undergoing transcatheter aortic valve implantation (TAVI) has not been fully elucidated so far. OBJECTIVES: To assess whether the degree of CAD influences the prognosis of patients undergoing TAVI. METHODS: Before TAVI, all patients underwent revascularization of the proximal vessels or the left main stem if indicated (stenosis ≥70% or 50%, respectively). In 666 patients, we calculated the baseline (bSS) and residual SYNTAX Score (rSS) prior to TAVI. In patients with revascularization, we determined the SYNTAX Revascularization Index (SRI=(1-(rSS/bSS))∗100). We also assessed the SYNTAX Score II (SS-II), combining anatomical and clinical variables. The primary endpoint was 3-year all-cause mortality. RESULTS: Higher baseline and residual SYNTAX Score were associated with increased 3-year mortality (no CAD 26.2%, low bSS 34.8%, high bSS 46.8%; p=0.001, respectively, no CAD 25.9%, low rSS 31.4%, high rSS 41.5%; p=0.01). The extent of revascularization represented by the SRI was not associated with outcome. The SYNTAX Score II was also associated with increased 3-year mortality. However, baseline and residual SYNTAX Score as well as SYNTAX Score II did not independently predict mortality. CONCLUSION: The anatomic severity of CAD as assessed by the baseline and residual SYNTAX Score is associated with survival after TAVI. Coronary artery disease seems to reflect general comorbidity burden and is associated with a higher risk profile of the patient.

6 Article Kinetics of Circulating MicroRNAs in Response to Cardiac Stress in Patients With Coronary Artery Disease. 2017

Jansen, Felix / Schäfer, Lisa / Wang, Han / Schmitz, Theresa / Flender, Anna / Schueler, Robert / Hammerstingl, Christoph / Nickenig, Georg / Sinning, Jan-Malte / Werner, Nikos. ·Department of Internal Medicine II, Rheinische Friedrich-Wilhelms University, Bonn, Germany. · Department of Internal Medicine II, Rheinische Friedrich-Wilhelms University, Bonn, Germany nwerner@uni-bonn.de. ·J Am Heart Assoc · Pubmed #28751542.

ABSTRACT: BACKGROUND: Circulating microRNAs (miRNAs/miRs) are regulated in patients with coronary artery disease. The impact of transient coronary ischemia on circulating miRNA levels is unknown. We aimed to investigate circulating miRNA kinetics in response to cardiac stress in patients with or without significant coronary stenosis. METHODS AND RESULTS: Eighty of 105 screened patients with stable coronary artery disease underwent dobutamine stress echocardiography before coronary angiography. Nine circulating vascular miRNAs (miRNA-21, miRNA-26, miRNA-27a, miRNA-92a, miRNA-126-3p, miRNA-133a, miRNA-222, miRNA-223, and miRNA-199-5p) were quantified in plasma by reverse transcription polymerase chain reaction before, immediately after, and 4 and 24 hours after dobutamine stress echocardiography. Quantitative polymerase chain reaction revealed increased miRNA-21, miRNA-126-3p, and miRNA-222 levels at 24 hours after dobutamine stress echocardiography in all patients. On coronary angiography, significant coronary artery stenoses (>80% diameter stenosis) were found in 41 patients. Stratifying patients according to the prevalence of significant stenoses, patients with stenosis showed an increase of circulating miRNA-21, miRNA-126-3p, and miRNA-222 in response to cardiac stress. In patients without significant stenoses (<50% diameter stenosis), miRNA-92a levels gradually increased in response to cardiac stress. CONCLUSIONS: miRNAs are distinctly released into the circulation in response to cardiac stress depending on the prevalence of significant coronary stenoses.

7 Article Invasive coronary angiography in patients with acute exacerbated COPD and elevated plasma troponin. 2016

Pizarro, Carmen / Herweg-Steffens, Neele / Buchenroth, Martin / Schulte, Wolfgang / Schaefer, Christian / Hammerstingl, Christoph / Werner, Nikos / Nickenig, Georg / Skowasch, Dirk. ·Department of Internal Medicine II - Cardiology, Pneumology and Angiology, University Hospital Bonn, Bonn, Germany. · Department of Pneumology, Johanniter Hospital Bonn, Bonn, Germany. · Department of Pneumology, Malteser Hospital Bonn/Rhein-Sieg, Bonn, Germany. ·Int J Chron Obstruct Pulmon Dis · Pubmed #27695304.

ABSTRACT: BACKGROUND: In acute exacerbation of COPD, increased plasma levels of cardiac troponin are frequent and associated with increased mortality. Thus, we aimed at prospectively determining the diagnostic value of coronary angiography in patients with exacerbated COPD and concomitantly elevated cardiac troponin. PATIENTS AND METHODS: A total of 88 patients (mean age 72.9±9.2 years, 56.8% male) hospitalized for acute exacerbation of COPD with elevated plasma troponin were included. All patients underwent coronary angiography within 72 hours after hospitalization. Complementary 12-lead electrocardiogram, transthoracic echocardiography, pulmonary function, and angiological testing were performed. RESULTS: Coronary angiography objectified the presence of ischemic heart disease (IHD) in 59 patients (67.0%), of whom 34 patients (38.6% of total study population) underwent percutaneous coronary intervention. Among these 34 intervened patients, the vast majority (n=26, 76.5%) had no previously known IHD, whereas only eight out of 34 patients (23.5%) presented an IHD history. Patients requiring coronary intervention showed significantly reduced left ventricular ejection fraction (45.8%±13.1% vs 55.1%±13.3%, CONCLUSION: Angiographically confirmed IHD that required revascularization occurred in 38.6% of exacerbated COPD patients with elevated cardiac troponin. In this considerable portion of patients, coronary angiography emerged to be of diagnostic and therapeutic value.

8 Article Endothelial microparticles reduce ICAM-1 expression in a microRNA-222-dependent mechanism. 2015

Jansen, Felix / Yang, Xiaoyan / Baumann, Katharina / Przybilla, David / Schmitz, Theresa / Flender, Anna / Paul, Kathrin / Alhusseiny, Adil / Nickenig, Georg / Werner, Nikos. ·Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany. · Feinberg Cardiovascular Research Institute, Northwestern University School of Medicine, Chicago, IL, USA. ·J Cell Mol Med · Pubmed #26081516.

ABSTRACT: Endothelial microparticles (EMP) are released from activated or apoptotic endothelial cells (ECs) and can be taken up by adjacent ECs, but their effect on vascular inflammation after engulfment is largely unknown. We sought to determine the role of EMP in EC inflammation. In vitro, EMP treatment significantly reduced tumour necrosis factor-α-induced endothelial intercellular adhesion molecule (ICAM)-1 expression on mRNA and protein level, whereas there was no effect on vascular cell adhesion molecule-1 expression. Reduced ICAM-1 expression after EMP treatment resulted in diminished monocyte adhesion in vitro. In vivo, systemic treatment of ApoE-/- mice with EMP significantly reduced murine endothelial ICAM-1 expression. To explore the underlying mechanisms, Taqman microRNA array was performed and microRNA (miR)-222 was identified as the strongest regulated miR between EMP and ECs. Following experiments demonstrated that miR-222 was transported into recipient ECs by EMP and functionally regulated expression of its target protein ICAM-1 in vitro and in vivo. After simulating diabetic conditions, EMP derived from glucose-treated ECs contained significantly lower amounts of miR-222 and showed reduced anti-inflammatory capacity in vitro and in vivo. Finally, circulating miR-222 level was diminished in patients with coronary artery disease (CAD) compared to patients without CAD. EMPs promote anti-inflammatory effects in vitro and in vivo by reducing endothelial ICAM-1 expression via the transfer of functional miR-222 into recipient cells. In pathological hyperglycaemic conditions, EMP-mediated miR-222-dependent anti-inflammatory effects are reduced.

9 Article Influence of intimal Chlamydophila pneumoniae persistence on cardiovascular complications after coronary intervention. 2015

Tuleta, I / Reek, D / Braun, P / Bauriedel, G / Nickenig, G / Skowasch, D / Andrié, R. ·Department of Internal Medicine II, Cardiology and Pulmonology, University of Bonn, Bonn, Germany, izabela.tuleta@ukb.uni-bonn.de. ·Infection · Pubmed #25344890.

ABSTRACT: PURPOSE: Chlamydophila pneumoniae has been implicated in atherosclerosis/restenosis; however, clear evidence is missing. Therefore, the aim of our study was to examine the influence of intimal infection and systemic inflammation on cardiovascular complications after coronary intervention. METHODS: 45 atheroma specimens from patients with symptomatic coronary artery disease who underwent directional endatherectomy with stent implantation were analyzed by immunohistochemistry to detect chlamydial (c) and human (h) heat shock protein (HSP) 60. The antibodies used against cHSP60 and hHSP60 were characterized by specificity and lack of cross immunoreactivity. In addition, serum Ig antibodies against Chlamydophila pneumoniae and against mycobacterial (m) HSP65 as well as serum CRP levels were measured. At follow-up of 6 months, quantitative coronary angiography was performed and major adverse cardiac events (MACE) were assessed. RESULTS: Atheroma specimens of all 10 patients with MACE were positive for cHSP60 with overall higher cHSP60 tissue expressions (1.1 ± 0.4 %) and serum CRP levels (2.18 ± 0.85 mg/dl) compared to the remaining 35 patients without MACE (7 of 35 specimens positive for cHSP60, mean cHSP60 expression: 0.4 ± 0.1 %, CRP levels: 0.67 ± 0.16 mg/dl, p < 0.05). Colocalization of both HSP60 homologues was more frequent in the MACE group. Anti-mHSP65 serum titers were significantly higher in MACE (1:510) versus non-MACE patients (1:335) and correlated positively with plaque expressions of cHSP60 and hHSP60 (r = 0.54, p < 0.05; r = 0.46, p < 0.05; resp.). CONCLUSIONS: Intimal presence of cHSP60, systemic CRP and antibodies against mHSP65 are predictors for occurrence of MACE after coronary intervention.

10 Article Influence of smoking dosage and chronic obstructive lung disease on the incidence of appropriate therapies and mortality in patients with structural heart disease and an implantable cardioverter defibrillator. 2015

Kreuz, Jens / Skowasch, Dirk / Kamrath, Philip / Lorenzen, Henning / Tiyerili, Vedat / Linhart, Markus / Nickenig, Georg / Schwab, Jörg O. ·Department of Medicine, Cardiology/Pneumology, University Hospital Bonn, Bonn, Germany. ·Pacing Clin Electrophysiol · Pubmed #25196490.

ABSTRACT: BACKGROUND: Smoking is known as a relevant risk factor for severe cardiac morbidities and mortality. This study was initiated to explore the influence of smoking dosage and presence of chronic obstructive lung disease (COPD) on the incidence of appropriate implantable cardioverter defibrillator (ICD) interventions and on mortality. METHODS: Prior studies on patients equipped with an ICD suggested that nicotine consumption increases the risk of experiencing an appropriate ICD therapy. There is no substantial data regarding the influence of cigarette smoking dosage on overall mortality in such endangered patients. A total of 349 patients with structural heart disease, either coronary artery disease or nonischemic cardiomyopathy equipped with an ICD, were included. Every patient answered a questionnaire regarding his smoking status and performed a spirometry and body plethysmography. RESULTS: A total of 104 patients (30%) suffered from COPD. Fifty-eight patients (17%) were "current smokers," 196 patients (56%) were revealed as "former smokers," while 93 (27%) patients were registered as "never smokers." A total of 163 patients (47%) received at least one appropriate ICD intervention during follow-up (median 48 ± 8 months). Twenty-three patients died during this study (6.6%). There was no association of COPD with the incidence of appropriate ICD therapies or mortality. Smoking dosage revealed as a significant risk factor for both appropriate ICD interventions (hazard ratio [HR] 1.5 for 60 pack years [PY] P = 0.04) and mortality (HR 2.3 for 60 PY P = 0.02). CONCLUSION: This study demonstrates a dose-related increased risk of smokers for appropriate ICD interventions and mortality. The results of this trail urge a strict nicotine abstinence, especially in patients with a structural heart disease undergoing ICD therapy.

11 Article MicroRNA expression in circulating microvesicles predicts cardiovascular events in patients with coronary artery disease. 2014

Jansen, Felix / Yang, Xiaoyan / Proebsting, Sebastian / Hoelscher, Marion / Przybilla, David / Baumann, Katharina / Schmitz, Theresa / Dolf, Andreas / Endl, Elmar / Franklin, Bernardo S / Sinning, Jan-Malte / Vasa-Nicotera, Mariuca / Nickenig, Georg / Werner, Nikos. ·Department of Internal Medicine II, Rheinische Friedrich-Wilhelms University, Bonn, Germany (F.J., S.P., M.H., D.P., K.B., T.S., J.M.S., M.V.N., G.N., N.W.). · Feinberg Cardiovascular Research Institute, Northwestern University School of Medicine, Chicago, IL (X.Y.). · Institute of Molecular Medicine, Rheinische Friedrich-Wilhelms University, Bonn, Germany (A.D., E.E.). · Institute of Innate Immunity, Rheinische Friedrich-Wilhelms University, Bonn, Germany (B.S.F.). ·J Am Heart Assoc · Pubmed #25349183.

ABSTRACT: BACKGROUND: Circulating microRNAs (miRNAs) are differentially regulated and selectively packaged in microvesicles (MVs). We evaluated whether circulating vascular and endothelial miRNAs in patients with stable coronary artery disease have prognostic value for the occurrence of cardiovascular (CV) events. METHODS AND RESULTS: Ten miRNAs involved in the regulation of vascular performance-miR-126, miR-222, miR-let7d, miR-21, miR-20a, miR-27a, miR-92a, miR-17, miR-130, and miR-199a-were quantified in plasma and circulating MVs by reverse transcription polymerase chain reaction in 181 patients with stable coronary artery disease. The median duration of follow-up for major adverse CV event-free survival was 6.1 years (range: 6.0-6.4 years). Events occurred in 55 patients (31.3%). There was no significant association between CV events and plasma level of the selected miRNAs. In contrast, increased expression of miR-126 and miR-199a in circulating MVs was significantly associated with a lower major adverse CV event rate. In univariate analysis, above-median levels of miR-126 in circulating MVs were predictors of major adverse CV event-free survival (hazard ratio: 0.485 [95% CIAUTHOR: Is 95% CI correct?: 0.278 to 0.846]; P=0.007) and percutaneous coronary interventions (hazard ratio: 0.458 [95% CI: 0.222 to 0.945]; P=0.03). Likewise, an increased level of miR-199a in circulating MVs was associated with a reduced risk of major adverse CV events (hazard ratio: 0.518 [95% CI: 0.299 to 0.898]; P=0.01) and revascularization (hazard ratio: 0.439 [95% CI: 0.232 to 0.832]; P=0.01) in univariate analysis. miRNA expression analysis in plasma compartments revealed that miR-126 and miR-199a are present mainly in circulating MVs. MV-sorting experiments showed that endothelial cells and platelets were found to be the major cell sources of MVs containing miR-126 and miR-199a, respectively. CONCLUSION: MVs containing miR-126 and miR-199a but not freely circulating miRNA expression predict the occurrence of CV events in patients with stable coronary artery disease.

12 Article Endothelial microparticle-mediated transfer of MicroRNA-126 promotes vascular endothelial cell repair via SPRED1 and is abrogated in glucose-damaged endothelial microparticles. 2013

Jansen, Felix / Yang, Xiaoyan / Hoelscher, Marion / Cattelan, Arianna / Schmitz, Theresa / Proebsting, Sebastian / Wenzel, Daniela / Vosen, Sarah / Franklin, Bernardo S / Fleischmann, Bernd K / Nickenig, Georg / Werner, Nikos. ·Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany (F.J., M.H., A.C., T.S., S.P., G.N., N.W.) · Feinberg Cardiovascular Research Institute, Northwestern University School of Medicine, Chicago, IL (X.Y.) · Institute of Physiology, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany (D.W., S.V., B.K.F.) · and Institute of Innate Immunity, Rheinische Friedrich-Wilhelms University, Bonn, Germany (B.S.F.). ·Circulation · Pubmed #24014835.

ABSTRACT: BACKGROUND: Repair of the endothelium after vascular injury is crucial for preserving endothelial integrity and preventing the development of vascular disease. The underlying mechanisms of endothelial cell repair are largely unknown. We sought to investigate whether endothelial microparticles (EMPs), released from apoptotic endothelial cells (ECs), influence EC repair. METHODS AND RESULTS: Systemic treatment of mice with EMPs after electric denudation of the endothelium accelerated reendothelialization in vivo. In vitro experiments revealed that EMP uptake in ECs promotes EC migration and proliferation, both critical steps in endothelial repair. To dissect the underlying mechanisms, Taqman microRNA array was performed, and microRNA (miR)-126 was identified as the predominantly expressed miR in EMPs. The following experiments demonstrated that miR-126 was transported into recipient human coronary artery endothelial cells by EMPs and functionally regulated the target protein sprouty-related, EVH1 domain-containing protein 1 (SPRED1). Knockdown of miR-126 in EMPs abrogated EMP-mediated effects on human coronary artery endothelial cell migration and proliferation in vitro and reendothelialization in vivo. Interestingly, after simulating diabetic conditions, EMPs derived from glucose-treated ECs contained significantly lower amounts of miR-126 and showed reduced endothelial repair capacity in vitro and in vivo. Finally, expression analysis of miR-126 in circulating microparticles from 176 patients with stable coronary artery disease with and without diabetes mellitus revealed a significantly reduced miR-126 expression in circulating microparticles from diabetic patients. CONCLUSIONS: Endothelial microparticles promote vascular endothelial repair by delivering functional miR-126 into recipient cells. In pathological hyperglycemic conditions, EMP-mediated miR-126-induced EC repair is altered.

13 Article Combination of angiographic and clinical characteristics for the prediction of clinical outcomes in elderly patients undergoing multivessel PCI. 2013

Sinning, Jan-Malte / Asdonk, Tobias / Erlhöfer, Christoph / Vasa-Nicotera, Mariuca / Grube, Eberhard / Nickenig, Georg / Werner, Nikos. ·Department of Medicine II, Heart Center Bonn, University Hopsital Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany, jan-malte.sinning@ukb.uni-bonn.de. ·Clin Res Cardiol · Pubmed #23881543.

ABSTRACT: BACKGROUND: Risk stratification is essential for the clinical decision-making process in elderly patients undergoing multivessel revascularization, since the optimal revascularization strategy remains subject of ongoing debate. AIMS: To assess the prognostic value of angiographic versus clinical characteristics for the prediction of a first adverse cardiac and cerebrovascular events (MACCE) (all-cause mortality, non-fatal myocardial infarction, stroke, and target lesion revascularization) and to develop a combined risk model. METHODS: After multivessel percutaneous coronary intervention (MV-PCI), SYNTAX score and EuroSCORE were calculated as combined risk model in 328 elderly patients who were followed up for a first MACCE. RESULTS: 328 patients with a mean age of 77.5 ± 5.1 years were followed up for 2.7 ± 1.5 years. A first MACCE occurred in 50.0 % (164/328) of the patients. To improve predictability, a combined risk score model with receiver operating characteristic curve validated cut-off values for EuroSCORE (>5 %) and SYNTAX score (>25) was developed. High risk patients had a 3.5-fold higher risk for MACCE after 3 years (HR 7.1, 95 % CI 1.9-6.5; p < 0.001). CONCLUSIONS: For adequate risk assessment in elderly patients undergoing MV-PCI, consideration of both comorbidities and coronary anatomic complexity is essential. A combined angiographic and clinical risk score provides superior prediction of 3-year MACCE risk in elderly patients.

14 Article Combination of angiographic and clinical characteristics for the prediction of clinical outcomes in patients undergoing unprotected left main coronary artery stenting. 2012

Sinning, Jan-Malte / Stoffel, Viktoria / Grube, Eberhard / Nickenig, Georg / Werner, Nikos. ·Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn, Rheinische Friedrich-Wilhelms-Universität, Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. ·Clin Res Cardiol · Pubmed #22286320.

ABSTRACT: BACKGROUND: Risk stratification is essential for the clinical decision-making process in patients undergoing revascularization of the unprotected left main coronary artery (ULMCA), since the optimal revascularization strategy still remains subject of ongoing debate. OBJECTIVES: To assess the prognostic value of angiographic versus clinical characteristics for the prediction of major adverse cardiac events (MACE) and to develop a combined risk model. METHODS: In 115 patients, who were followed up for MACE after ULMCA stenting, SYNTAX score and EuroSCORE have been calculated for a combined risk model. RESULTS: Whereas the SYNTAX score was not able to predict MACE at 1 year (32.8 ± 11.7 vs. 29.1 ± 12.2, P = 0.13), the logistic EuroSCORE was significantly increased in these patients suffering a MACE at 1 year [11.9 (4.4/22.6) vs. 4.8 (2.3/14.6)%, P = 0.007]. With ROC curve validated cut-off values, the combination of EuroSCORE (>7.5%) and SYNTAX score (>25) provided incremental predictive value for risk stratification of ULMCA patients (AUC 0.71, 95% CI 0.62-0.79, P < 0.001). This combined risk model was associated with the rate of cardiac mortality (P = 0.04), non-fatal myocardial infarction (P = 0.005), and target lesion revascularization (P = 0.04) and was superior to the SYNTAX score alone (P = 0.03). High risk patients had a 7.1-fold higher risk for MACE (HR 7.1. 95% CI 2.1-24.1, P = 0.002) after 1 year. CONCLUSIONS: For adequate risk assessment in ULMCA patients, consideration of both comorbidities and coronary anatomic complexity, is essential. A combination of angiographic and clinical risk scores improves the prognostic value for the prediction of 1-year MACE risk and is superior to stand-alone scores.

15 Article Angiotensin II impairs endothelial progenitor cell number and function in vitro and in vivo: implications for vascular regeneration. 2011

Endtmann, Cathleen / Ebrahimian, Talin / Czech, Thomas / Arfa, Omar / Laufs, Ulrich / Fritz, Mathias / Wassmann, Kerstin / Werner, Nikos / Petoumenos, Vasileios / Nickenig, Georg / Wassmann, Sven. ·Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Côte-Ste-Catherine Rd, Montréal, Québec H3T 1E2, Canada. ·Hypertension · Pubmed #21825227.

ABSTRACT: Endothelial progenitor cells (EPCs) contribute to endothelial regeneration. Angiotensin II (Ang II) through Ang II type 1 receptor (AT(1)-R) activation plays an important role in vascular damage. The effect of Ang II on EPCs and the involved molecular mechanisms are incompletely understood. Stimulation with Ang II decreased the number of cultured human early outgrowth EPCs, which express both AT(1)-R and Ang II type 2 receptor, mediated through AT(1)-R activation and induction of oxidative stress. Ang II redox-dependently induced EPC apoptosis through increased apoptosis signal-regulating kinase 1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase phosphorylation; decreased Bcl-2 and increased Bax expression; and activation of caspase 3 but had no effect on the low cell proliferation. In addition, Ang II impaired colony-forming and migratory capacities of early outgrowth EPCs. Ang II infusion diminished numbers and functional capacities of EPCs in wild-type (WT) but not AT(1)a-R knockout mice (AT(1)a(-/-)). Reendothelialization after focal carotid endothelial injury was decreased during Ang II infusion. Salvage of reendothelialization by intravenous application of spleen-derived progenitor cells into Ang II-treated WT mice was pronounced with AT(1)a(-/-) cells compared with WT cells, and transfusion of Ang II-pretreated WT cells into WT mice without Ang II infusion was associated with less reendothelialization. Transplantation of AT(1)a(-/-) bone marrow reduced atherosclerosis development in cholesterol-fed apolipoprotein E-deficient mice compared with transplantation of apolipoprotein E-deficient or WT bone marrow. Randomized treatment of patients with stable coronary artery disease with the AT(1)-R blocker telmisartan significantly increased the number of circulating CD34/KDR-positive EPCs. Ang II through AT(1)-R activation, oxidative stress, and redox-sensitive apoptosis signal-regulating kinase 1-dependent proapoptotic pathways impairs EPCs in vitro and in vivo, resulting in diminished vascular regeneration.

16 Article Prevalence of intimal heat shock protein 60 homologues in unstable angina and correlation with anti-heat shock protein antibody titers. 2011

Andrié, René P / Bauriedel, Gerhard / Braun, Peter / Höpp, Hans W / Nickenig, Georg / Skowasch, Dirk. ·Department of Internal Medicine II/Cardiology, University of Bonn, Sigmund-Freud-Strasse 25, Bonn, Germany. Rene.Andrie@ukb.uni-bonn.de ·Basic Res Cardiol · Pubmed #21416407.

ABSTRACT: Heat shock proteins (HSPs) are among the most highly conserved and immunogenic proteins shared by microbial agents and mammals. Human (h) HSP60 is upregulated under stress conditions and serves as a target for cross-reactive cytotoxic HSP-serum-antibodies. The present study evaluates the expressions of hHSP60 and its homologue chlamydial (c) HSP60 in advanced human coronary lesions and correlates intimal tissue-bound HSP expressions with circulating HSP-antibodies. Coronary atherectomy specimens retrieved from 100 primary target lesions of patients with unstable angina (UA; n = 40) or stable angina (SA; n = 60) were assessed immunohistochemically for the presence of hHSP60 and cHSP60. In a subgroup (n = 40), blood samples were tested for anti-Chl. pn.-IgG/IgA-titers and anti-HSP65-antibody titers. Coronary plaques revealed immunoreactive hHSP60 in 55% and cHSP60 in 45% of the lesions. Expression of both HSP homologues was significantly (each p < 0.001) higher in UA lesions compared with SA lesions (7.4 vs. 1.2% and 6.0 vs. 1.1%). HSP homologues showed positive correlations both in UA- and SA-lesions (r = 0.41, 0.33; p < 0.05). cHSP60 showed no association with anti-Chl. pn.-IgG/IgA-titers, whereas expressions of both homologues correlated positive with anti-HSP65-Ab titers (r = 0.42, p < 0.05; r = 0.50, p < 0.01). Intimal amounts of HSP60 homologues were associated with increased expressions of C-reactive protein, Toll-like receptor-4 and tissue factor. Human and chlamydial HSP60 colocalize within coronary atheroma, most prevalent in lesions associated with UA. Our data demonstrate a significant correlation between the intimal expressions of HSP60 homologues and serum HSP65 antibodies, thereby suggesting that humoral immune reactions may play an important role in coronary atherosclerosis and plaque instability.

17 Article Circulating CD31+/Annexin V+ microparticles correlate with cardiovascular outcomes. 2011

Sinning, Jan-Malte / Losch, Jan / Walenta, Katrin / Böhm, Michael / Nickenig, Georg / Werner, Nikos. ·Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany. ·Eur Heart J · Pubmed #21186238.

ABSTRACT: AIMS: CD31+/Annexin V+ microparticles (MPs) are increased in patients with cardiovascular risk factors and impaired coronary endothelial function. We evaluated whether MPs are an independent marker for cardiovascular events in patients with stable coronary artery disease (CAD). METHODS AND RESULTS: The number of CD31+/Annexin V+ MP was determined by flow cytometry in 200 patients (age 66.1±10.4 years) and correlated with cardiovascular outcomes. The median follow-up time for major adverse cardiovascular and cerebral event (MACCE)-free survival was 6.1 (6.0/6.4) years. Four patients were lost to follow-up. A first MACCE occurred in 72 patients (37%). Microparticle levels were significantly higher in patients with MACCE compared with patients without event (P=0.004). The prevalence of diabetes (P=0.02) and male gender (P=0.05) was significantly related to the MP level. In multivariate analysis (cardiovascular risk factors, number of diseased vessels, use of angiotensin-converting enzyme-inhibitors and statins), high MP levels were associated with a higher risk for cardiovascular death [Hazard ratio (HR) 4.0, 95% confidence interval (CI) 1.1-14.6; P=0.04], the need for revascularization (HR 2.4, 95% CI 1.3-4.4; P=0.005), and the occurrence of a first MACCE (HR 2.3, 95% CI 1.4-3.8; P=0.001). Inclusion of the MP level into a classical risk factor model substantially increased c-statistics from 0.637 (95% CI: 0.557-0.717) to 0.702 (95% CI: 0.625-0.780) (P=0.03). CONCLUSION: The level of circulating CD31+/Annexin V+ MPs is an independent predictor of cardiovascular events in stable CAD patients and may be useful for risk stratification.

18 Minor Antiplatelet effects of n-3 polyunsaturated fatty acids compared with aspirin: a pilot study with whole-blood aggregometry. 2009

Tuleta, Izabela / Bauriedel, Gerhard / Hasenbank, Ina / Andrié, René / Pabst, Stefan / Nickenig, Georg / Skowasch, Dirk. · ·Thromb Res · Pubmed #19457547.

ABSTRACT: -- No abstract --