Lankeit, Mareike

[["dc.bibliographiccitation.issue","18"],["dc.bibliographiccitation.journal","Circulation"],["dc.bibliographiccitation.volume","118"],["dc.contributor.author","Dallas, Claudia"],["dc.contributor.author","Lankeit, Mareike K."],["dc.contributor.author","Puls, Miriam"],["dc.contributor.author","Schaefer, Katrin"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Konstantinides, Stavros V."],["dc.date.accessioned","2018-11-07T11:09:52Z"],["dc.date.available","2018-11-07T11:09:52Z"],["dc.date.issued","2008"],["dc.format.extent","S621"],["dc.identifier.isi","000262104501728"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53094"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.publisher.place","Philadelphia"],["dc.relation.conference","81st Annual Scientific Session of the American-Heart-Association"],["dc.relation.eventlocation","New Orleans, LA"],["dc.relation.issn","0009-7322"],["dc.title","Heart-Type Fatty Acid-Binding Protein Predicts Outcome In Normotensive Patients With Pulmonary Embolism"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","996"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Thrombosis and Haemostasis"],["dc.bibliographiccitation.lastpage","1003"],["dc.bibliographiccitation.volume","111"],["dc.contributor.author","Dellas, Claudia"],["dc.contributor.author","Tschepe, Merle"],["dc.contributor.author","Seeber, Valerie"],["dc.contributor.author","Zwiener, Isabella"],["dc.contributor.author","Kuhnert, Katherina"],["dc.contributor.author","Schaefer, Katrin"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Konstantinides, Stavros"],["dc.contributor.author","Lankeit, Mareike"],["dc.date.accessioned","2017-09-07T11:46:17Z"],["dc.date.available","2017-09-07T11:46:17Z"],["dc.date.issued","2014"],["dc.description.abstract","We tested whether heart-type fatty acid binding protein (H-FABP) measured by a fully-automated immunoturbidimetric assay in comparison to ELISA provides additive prognostic value in patients with pulmonary embolism (PE), and validated a fast prognostic score in comparison to the ESC risk prediction model and the simplified Pulmonary Embolism Severity Index (sPESI). We prospectively examined 271 normotensive patients with PE; of those, 20 (7%) had an adverse 30-day outcome. H-FABP levels determined by immunoturbidimetry were higher (median, 5.2 [IQR; 2.7-9.8] ng/ml) than those by ELISA (2.9 [1.1-5.4] ng/ml), but Bland-Altman plot demonstrated a good agreement of both assays. The area under the curve for H-FABP was greater for immunoturbidimetry than for ELISA (0.82 [0.74-0.91] vs 0.78 [0.68-0.89]; P=0.039). H-FABP measured by immunoturbidimetry (but not by ELISA) provided additive prognostic information to other predictors of 30-day outcome (OR, 12.4 [95% CI, 1.6-97.6]; P=0.017).When H-FABP determined by immunoturbidimetry was integrated into a novel prognostic score (H-FABP, Syncope, and Tachycardia; FAST score), the score provided additive prognostic information by multivariable analysis (OR, 14.2 [3.9-51.4]; p<0.001; c-index, 0.86) which were superior to information obtained by the ESC model(c-index, 0.62; net reclassification improvement (NRI), 0.39 [0.21-0.56]; P<0.001) or the sPESI (c-index, 0.68; NRI, 0.24 [0.05-0.43]; P=0.012). In conclusion, determination of H-FABP by immunoturbidimetry provides prognostic information superior to that of ELISA and, if integrated in the FAST score, appears more suitable to identify patients with an adverse 30-day outcome compared to the ESC model and sPESI."],["dc.identifier.doi","10.1160/TH13-08-0663"],["dc.identifier.gro","3142135"],["dc.identifier.isi","000335541500025"],["dc.identifier.pmid","24477222"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4933"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Schattauer Gmbh-verlag Medizin Naturwissenschaften"],["dc.relation.issn","0340-6245"],["dc.title","A novel H-FABP assay and a fast prognostic score for risk assessment of normotensive pulmonary embolism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","796"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Thrombosis Research"],["dc.bibliographiccitation.lastpage","801"],["dc.bibliographiccitation.volume","135"],["dc.contributor.author","Klok, F. A."],["dc.contributor.author","Tesche, C."],["dc.contributor.author","Rappold, L."],["dc.contributor.author","Dellas, Claudia"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Huisman, M. V."],["dc.contributor.author","Konstantinides, Stavros"],["dc.contributor.author","Lankeit, Mareike"],["dc.date.accessioned","2017-09-07T11:44:25Z"],["dc.date.available","2017-09-07T11:44:25Z"],["dc.date.issued","2015"],["dc.description.abstract","Purpose: International guidelines do not provide strong recommendations on the duration and intensity of follow-up after acute pulmonary embolism(PE), nor on screening-programs for chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to address this gab by performing an external validation of the easy \"CTEPH rule-out-criteria\" based on a normal NT-proBNP level and the absence of 3 ECG characteristics. Methods: 134 patients underwent clinical follow-up 6 months after PE. Predefined transthoracic echocardiographic (TTE) criteria were used to categorize patients as \"PH unlikely\" or \"PH possible/likely\". The latter patients underwent further (invasive) diagnostic procedures to confirm and classify the diagnosis of pulmonary hypertension. NT-proBNP and ECGs, both assessed at the day of echocardiography, were evaluated post-hoc. Results: Sixty-three patients (47%) scored none of the \"CTEPH rule-out criteria\" positive, of whom 61 had normal TTE (97%). Twenty-five patients (19%) were categorized by TTE as \"PH possible/likely\"; of those, 6 were diagnosed with CTEPH. The sensitivity of rule-out criteria for CTEPH was 100% (95%CI 56-100%; 6/6 patients identified), and for \"PH possible/likely\" on TTE 92% (95%CI 74-99%; 23/25 patients identified): 2 asymptomatic patients with estimated systolic pulmonary arterial pressure of 36 mmHg and 38 mmHg, respectively, who remained stable during further 2-year follow-up, were not identified. Inter-observer agreement for the adjudication of the ECG characteristics was excellent (kappa-statistic 0.97). Conclusions: In this external validation cohort, we confirmed the diagnostic accuracy and reproducibility of the \"CTEPH rule-out criteria\". These results provide a solid ground for future outcome trials applying this algorithm. (C) 2014 Published by Elsevier Ltd."],["dc.identifier.doi","10.1016/j.thromres.2014.12.009"],["dc.identifier.gro","3141915"],["dc.identifier.isi","000353490800005"],["dc.identifier.pmid","25746363"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2489"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.relation.issn","0049-3848"],["dc.title","External validation of a simple non-invasive algorithm to rule out chronic thromboembolic pulmonary hypertension after acute pulmonary embolism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","121"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Thrombosis and Haemostasis"],["dc.bibliographiccitation.lastpage","128"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Klok, F. A."],["dc.contributor.author","Dzikowska-Diduch, O."],["dc.contributor.author","Kostrubiec, Maciej"],["dc.contributor.author","Vliegen, H. W."],["dc.contributor.author","Pruszczyk, Piotr"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Huisman, M. V."],["dc.contributor.author","Konstantinides, Stavros"],["dc.contributor.author","Lankeit, Mareike"],["dc.date.accessioned","2017-09-07T11:54:44Z"],["dc.date.available","2017-09-07T11:54:44Z"],["dc.date.issued","2016"],["dc.description.abstract","Introduction: Validated risk factors for the diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary embolism (PE) are currently lacking. Methods: This is a post hoc patient-level analysis of three large prospective cohorts with a total of 772 consecutive patients with acute PE, without major cardiopulmonary or malignant comorbidities. All underwent echocardiography after a median of 1.5 years. In cases with signs of pulmonary hypertension, additional diagnostic tests to confirm CTEPH were performed. Baseline demographics and clinical characteristics of the acute PE event were included in a multivariable regression analysis. Independent predictors were combined in a clinical prediction score. Results: CTEPH was confirmed in 22 patients (2.8%) by right heart catheterization. Unprovoked PE, known hypothyroidism, symptom onset > 2 weeks before PE diagnosis, right ventricular dysfunction on computed tomography or echocardiography, known diabetes mellitus and thrombolytic therapy or embolectomy were independently associated with a CTEPH diagnosis during follow-up. The area under the receiver operating charateristic curve (AUC) of the prediction score including those six variables was 0.89 (95% confidence interval [ CI] 0.84-0.94). Sensitivity analysis and bootstrap internal validation confirmed this AUC. Seventy-three per cent of patients were in the low-risk category (CTEPH incidence of 0.38%, 95% CI 0-1.5%) and 27% were in the high-risk category (CTEPH incidence of 10%, 95% CI 6.5-15%). Conclusion: The 'CTEPH prediction score' allows for the identification of PE patients with a high risk of CTEPH diagnosis after PE. If externally validated, the score may guide targeting of CTEPH screening to at-risk patients."],["dc.identifier.doi","10.1111/jth.13175"],["dc.identifier.gro","3141751"],["dc.identifier.isi","000370661100014"],["dc.identifier.pmid","26509468"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/668"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: German Federal Ministry of Education and Research [BMBF 01EO1003]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley-blackwell"],["dc.relation.eissn","1538-7836"],["dc.relation.issn","1538-7933"],["dc.title","Derivation of a clinical prediction score for chronic thromboembolic pulmonary hypertension after acute pulmonary embolism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","204"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","International Journal of Obesity"],["dc.bibliographiccitation.lastpage","210"],["dc.bibliographiccitation.volume","37"],["dc.contributor.author","Dellas, Claudia"],["dc.contributor.author","Lankeit, Mareike"],["dc.contributor.author","Reiner, Christian"],["dc.contributor.author","Schaefer, Katrin"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Konstantinides, Stavros"],["dc.date.accessioned","2017-09-07T11:48:18Z"],["dc.date.available","2017-09-07T11:48:18Z"],["dc.date.issued","2013"],["dc.description.abstract","OBJECTIVE: The adipocytokine leptin is an independent cardiovascular risk factor and exerts prothrombotic effects, both in arterial and venous thrombosis. We therefore investigated the relationship between leptin levels and clinical outcome in patients with acute pulmonary embolism (PE). DESIGN: We prospectively studied consecutive patients with confirmed acute PE admitted at the University Hospital of Goettingen (Germany) between 2003 and 2009. SUBJECTS: The study subjects were a total of 264 patients with PE (median age, 68 years; interquartile range, 53-75; 60% women; body mass index (BMI) 27 kgm(-2) (24.1-31.2)). Leptin levels were determined by a commercially available enzyme-linked immunosorbent assay. Patients were followed for an adverse 30-day outcome, that is, death, circulatory collapse with need for catecholamines, intubation or resuscitation, and for long-term survival. RESULTS: The median leptin level was 10.1 ng ml(-1) (3.7-25.2). Patients (n = 49; 18.6%) with a complicated 30-day course had significantly lower leptin levels (5.3 ng ml(-1) (1.8-19.7) compared with patients without complications (10.4 ng ml(-1) (4.7-25.5), P = 0.02). When leptin was analyzed as a continuous variable, there was a significant 36% increase in the relative risk for early complications for every decrease in the natural logarithm of leptin by one s.d. (odds ratio (OR) 1.36 (1.06-1.76), P = 0.017), independently of BMI (BMI-adjusted OR, 1.52 (1.13-2.05), P = 0.006). In addition, patients within the lowest leptin tertile had a 2.8- and 2.3-fold increased risk for 30-day-complications, compared with those in the middle (P = 0.011) and high tertile (P = 0.030), and a worse probability of long-term survival (log-rank; P = 0.018). CONCLUSION: Low plasma leptin concentration is a predictor for a complicated course and high mortality in patients with acute PE. This association is independent of known factors affecting leptin levels, including gender and obesity. International Journal of Obesity (2013) 37, 204-210; doi:10.1038/ijo.2012.36; published online 20 March 2012"],["dc.identifier.doi","10.1038/ijo.2012.36"],["dc.identifier.gro","3142393"],["dc.identifier.isi","000316932100008"],["dc.identifier.pmid","22430305"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7786"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: University of Goettingen (Heidenreich von Siebold-Programm)"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","0307-0565"],["dc.title","BMI-independent inverse relationship of plasma leptin levels with outcome in patients with acute pulmonary embolism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","543"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Thrombosis Research"],["dc.bibliographiccitation.lastpage","547"],["dc.bibliographiccitation.volume","132"],["dc.contributor.author","Lankeit, Mareike"],["dc.contributor.author","Dellas, Claudia"],["dc.contributor.author","Benz, Viola"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Konstantinides, Stavros"],["dc.date.accessioned","2017-09-07T11:47:05Z"],["dc.date.available","2017-09-07T11:47:05Z"],["dc.date.issued","2013"],["dc.description.abstract","Background: Heart-type fatty acid-binding protein (H-FABP) is a useful biomarker for risk stratification of patients with pulmonary embolism(PE). In patients with acutemyocardial infarction, H-FABP plasma concentrations rise after 30 minutes and return to normal within 20-24 hours. We tested whether the predictive value of H-FABP is affected by the duration of symptoms prior to diagnosis in patients with PE. Material and Methods: We prospectively studied 257 consecutive normotensive patients with confirmed symptomatic PE. Results: Patients with acute (<24 hours; n = 150) symptom onset presented more often with syncope (28.7% vs. 6.5%; p < 0.001) compared to patients with symptoms >= 24 hours (n = 107); other baseline characteristics, comorbidities, and risk factors were distributed equally. Patients with an adverse 30-day outcome (6.6%) had higher H-FABP levels (11.84 [3.57-19.62] ng/ml) compared to patients with a favorable course (3.42 [1.92-5.42] ng/ml; p < 0.001). However, the proportion of patients with H-FABP levels >= 6 ng/ml did not differ among patients with acute symptom onset and late presentation (p = 0.104). Only tachycardia and elevation of H-FABP were associated with an increased risk of an adverse 30-day outcome both in patients with acute symptom onset (H-FABP: OR, 5.8; 95% CI, 1.4-24.5; p = 0.016; tachycardia: 7.0 [1.4-36.0]; p = 0.018) and late presentation (H-FABP: 9.3 [2.0-43.2]; p = 0.004 and tachycardia: 12.3 [1.5-103.6]; p = 0.021). The prognostic value could further be improved by the use of a simple H-FABP-based clinical prediction score. Conclusions: Our findings indicate that H-FABP is a useful biomarker for risk stratification of normotensive patients with PE regardless of symptom duration prior to diagnosis. (c) 2013 Published by Elsevier Ltd."],["dc.identifier.doi","10.1016/j.thromres.2013.09.022"],["dc.identifier.gro","3142264"],["dc.identifier.isi","000325752700010"],["dc.identifier.pmid","24094603"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/6354"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: German Federal Ministry of Education and Research [BMBF 01EO1003]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.relation.issn","0049-3848"],["dc.title","The predictive value of heart-type fatty acid-binding protein is independent from symptom duration in normotensive patients with pulmonary embolism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","173"],["dc.bibliographiccitation.journal","Thrombosis Research"],["dc.bibliographiccitation.lastpage","181"],["dc.bibliographiccitation.volume","178"],["dc.contributor.author","Keller, Karsten"],["dc.contributor.author","Rappold, Lisa"],["dc.contributor.author","Gerhold-Ay, Aslihan"],["dc.contributor.author","Hobohm, Lukas"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Konstantinides, Stavros V"],["dc.contributor.author","Dellas, Claudia"],["dc.contributor.author","Lankeit, Mareike"],["dc.date.accessioned","2020-12-10T15:21:34Z"],["dc.date.available","2020-12-10T15:21:34Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1016/j.thromres.2019.04.020"],["dc.identifier.issn","0049-3848"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73072"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Sex-specific differences in pulmonary embolism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","European Heart Journal"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Lankeit, Mareike K."],["dc.contributor.author","Kuhnert, K."],["dc.contributor.author","Stuebing, M."],["dc.contributor.author","Schaefer, K."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Konstantinides, Stavros V."],["dc.contributor.author","Dellas, Claudia"],["dc.date.accessioned","2018-11-07T09:07:23Z"],["dc.date.available","2018-11-07T09:07:23Z"],["dc.date.issued","2012"],["dc.format.extent","412"],["dc.identifier.isi","000308012403272"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25785"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.publisher.place","Oxford"],["dc.relation.eventlocation","Munchen, GERMANY"],["dc.relation.issn","0195-668X"],["dc.title","Risk stratification of non-high-risk pulmonary embolism by the use of a novel rapid immunoturbidimetric H-FABP assay"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1332"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Thrombosis and Haemostasis"],["dc.bibliographiccitation.lastpage","1346"],["dc.bibliographiccitation.volume","119"],["dc.contributor.author","Kölmel, Sebastian"],["dc.contributor.author","Hobohm, Lukas"],["dc.contributor.author","Käberich, Anja"],["dc.contributor.author","Krieg, Valentin J."],["dc.contributor.author","Bochenek, Magdalena L."],["dc.contributor.author","Wenzel, Philip"],["dc.contributor.author","Wiedenroth, Christoph B."],["dc.contributor.author","Liebetrau, Christoph"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Mayer, Eckhard"],["dc.contributor.author","Konstantinides, Stavros V."],["dc.contributor.author","Schäfer, Katrin"],["dc.contributor.author","Guth, Stefan"],["dc.contributor.author","Lankeit, Mareike"],["dc.date.accessioned","2019-08-06T12:12:56Z"],["dc.date.available","2019-08-06T12:12:56Z"],["dc.date.issued","2019"],["dc.description.abstract"," Inflammation and incomplete thrombus resolution leading to obstructive fibrotic remodelling are considered critical mechanisms for the development of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE). Osteopontin (OPN) is involved in a variety of biological processes including inflammation and tissue fibrosis."],["dc.identifier.doi","10.1055/s-0039-1692174"],["dc.identifier.pmid","31183846"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62313"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","2567-689X"],["dc.relation.issn","0340-6245"],["dc.relation.issn","2567-689X"],["dc.title","Potential Involvement of Osteopontin in Inflammatory and Fibrotic Processes in Pulmonary Embolism and Chronic Thromboembolic Pulmonary Hypertension"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1063"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Thrombosis and Haemostasis"],["dc.bibliographiccitation.lastpage","1071"],["dc.bibliographiccitation.volume","98"],["dc.contributor.author","Dellas, Claudia"],["dc.contributor.author","Schäfer, Katrin"],["dc.contributor.author","Rohm, Ilonka"],["dc.contributor.author","Lankeit, Mareike"],["dc.contributor.author","Leifheit, Maren"],["dc.contributor.author","Loskutoff, David J."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Konstantinides, Stavros V."],["dc.date.accessioned","2017-09-07T11:49:24Z"],["dc.date.available","2017-09-07T11:49:24Z"],["dc.date.issued","2007"],["dc.description.abstract","Leptin enhances agonist-induced platelet aggregation, and human platelets have been reported to express the leptin receptor. However, the pathways and mediators lying downstream of leptin binding to platelets remain, with few exceptions, unknown. In the present study, we sought to gain further insight into the possible role of leptin as a platelet agonist. Stimulation of platelets with leptin promoted thromboxane generation and activation of alpha(IIb)beta(3), as demonstrated by PAC-I binding. Furthermore, it increased the adhesion to immobilised fibrinogen (p < 0.001) and induced cytoskeletal rearrangement of both platelets and Meg01 cells. Leptin time- and dose-dependently phosphorylated the intracellular signalling molecules JAK2 and STAT3, although the importance of STAT3 for leptin-induced platelet activation remains to be determined. Important intracellular mediators and pathways activated by leptin downstream of JAK2 were found to include phosphaticlylinositol-3 kinase, phospholipase C gamma 2 and protein kinase C,as well as the p38 MAP kinase-phospholipase A(2) axis. Accordingly, incubation with the specific inhibitors AG490, Ly294002, U73122, and SB203580 prevented leptin-mediated platelet activation. These results help delineate biologically relevant leptin signalling pathways in platelets and may improve our understanding of the mechanisms linking hyperleptinaemia to the increased thrombosis risk in human obesity."],["dc.identifier.doi","10.1160/TH07-03-0213"],["dc.identifier.gro","3143420"],["dc.identifier.isi","000251064400021"],["dc.identifier.pmid","18000612"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/932"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: NCRR NIH HHS [M01 RR00833]; NHLBI NIH HHS [HL75736]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0340-6245"],["dc.title","Leptin signalling and leptin-mediated activation of human platelets: Importance of JAK2 and the phospholipases C gamma 2 and A(2)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]