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Universitäts-Herzzentrum Freiburg - Bad KrozingenUniversitäts-Herzzentrum Freiburg - Bad Krozingen

AG Thrombozytäre Heterogenität

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OVERVIEW

Platelets play a central role in the development of acute manifestations of atherothrombotic disease such as acute myocardial infarction and critical limb ischemia. Apart from being a central mechanism of thrombus formation, platelets and the coagulation system have also a key role in modulation of atherothrombotic diseases. However, the cellular mechanisms of platelets leading to atherogenesis and progression to adverse cardiovascular events are still not fully clarified.

We postulate that functional heterogeneity within the platelet pool is present and therefore specific platelet subpopulations contribute differently to progression of atherothrombotic diseases. In this context, we aim to characterize different aspects of platelet heterogeneity and identify the underlying mechanisms. To this end, we have established a protocol for sorting of functional platelets which allows detailed characterization of specific platelet subpopulations.

With respect to the subpopulation of newly formed platelets, named reticulated or immature platelets, our site has shown that higher levels of immature platelets are associated with an impaired response to therapy with P2Y12-antagonists. Further, the key mechanism of this finding was not sole platelet turnover as previously assumed but intrinsic properties of this platelet subtype. In this regard, we are currently performing an in-depth characterization of reticulated platelets.

MEMBERS:
Dr. med. Mark Zurek, Assistenzarzt
E-Mail: mark.zurek@universitaets-herzzentrum.de

Lucas Gegalski, Biotechnologischer Assistent
Tel.: 07633 402-4811
Fax: 07633 402-2489
E-Mail: lucas.gegalski@universitaets-herzzentrum.de

Prof. Dr. rer. nat. Dietmar Trenk
Tel.: 07633 402-2480
Fax: 07633 402-2489
E-Mail: dietmar.trenk@universitaets-herzzentrum.de

FORMER MEMBERS:
Dr. rer. nat. Laura Hille
Dr. med. Marco Cederqvist
Dr. med. Christian Stratz

PUBLICATIONS (last 5 years):

2020

Evaluation of Mortality Following Paclitaxel Drug-Coated Balloon Angioplasty of Femoropopliteal Lesions in the Real World.
Böhme T, Noory E, Beschorner U, Jacques B, Bürgelin K, Macharzina R, Gebauer E, Cheung F, Lechner P, Nührenberg T, Zeller T.
JACC Cardiovasc Interv. 2020 Jun 18:S1936-8798(20)31051-7

Ultrastructural, transcriptional, and functional differences between human reticulated and non-reticulated platelets.
Hille L, Lenz M, Vlachos A, Grüning B, Hein L, Neumann FJ, Nührenberg TG, Trenk D.
J Thromb Haemost. 2020 May 19. doi: 10.1111/jth.14895. Online ahead of print.

2019

Update ESC-Guideline: Myocardial Revascularization].
Behm P, Nührenberg T, Bönner F, Neumann FJ.
Dtsch Med Wochenschr. 2019 Oct;144(20):1417-1422.

Need for pacemaker implantation in patients with normal QRS duration immediately after transcatheter aortic valve implantation.
Schoechlin S, Jalil F, Blum T, Ruile P, Hein M, Nührenberg TG, Arentz T, Neumann FJ.
Europace. 2019 Oct 3. pii: euz261. doi: 10.1093/europace/euz261. [Epub ahead of print]

Antagonizing P2Y12 Receptor Inhibitors: Current and Future Options.
Trenk D, Hille L, Leggewie S, Stratz C, Nührenberg TG, Aradi D, Schrör K, Sibbing D.
Thromb Haemost. 2019 Oct;19(10):1606-1616.

Reply: Low Prevalence of High On-Treatment Platelet Reactivity for Both Aspirin and Clopidogrel After HALT and TAVR.
Nührenberg TG, Kille A, Neumann FJ, Stratz C, Ruile P.
JACC Cardiovasc Interv. 2019 May 13;12(9):895-896. doi: 10.1016/j.jcin.2019.03.001. No abstract available.

Evaluation of an Alternative Staining Method Using SYTO 13 to Determine Reticulated Platelets.
Hille L, Cederqvist M, Hromek J, Stratz C, Trenk D, Nührenberg TG.
Thromb Haemost. 2019 May;119(5):779-785.

Impact of On-Clopidogrel Platelet Reactivity on Incidence of Hypoattenuated Leaflet Thickening After Transcatheter Aortic Valve Replacement.
Nührenberg TG, Hromek J, Kille A, Hochholzer W, Hein M, Trenk D, Neumann FJ, Stratz C, Ruile P.
JACC Cardiovasc Interv. 2019 Jan 14;12(1):12-18. doi: 10.1016/j.jcin.2018.08.008. Epub 2018 Aug 27.

Effect of mineralocorticoid receptor antagonists on cardiac function in patients with heart failure and preserved ejection fraction: a systematic review and meta-analysis of randomized controlled trials.
Kapelios CJ, Murrow JR, Nührenberg TG, Montoro Lopez MN.
Heart Fail Rev. 2019 May;24(3):367-377. doi: 10.1007/s10741-018-9758-0. Review.

2018

A Randomized Trial to Assess Regional Left Ventricular Function After Stent Implantation in Chronic Total Occlusion: The REVASC Trial.
Mashayekhi K, Nührenberg TG, Toma A, Gick M, Ferenc M, Hochholzer W, Comberg T, Rothe J, Valina CM, Löffelhardt N, Ayoub M, Zhao M, Bremicker J, Jander N, Minners J, Ruile P, Behnes M, Akin I, Schäufele T, Neumann FJ, Büttner HJ.
JACC Cardiovasc Interv. 2018 Oct 8;11(19):1982-1991.

Long-term results after PCI of unprotected distal left main coronary artery stenosis: the Bifurcations Bad Krozingen (BBK)-Left Main Registry.
Ferenc M, Banholzer N, Hochholzer W, Mashayekhi K, Comberg T, Rothe J, Valina CM, Toma A, Löffelhardt N, Gick M, Neumann FJ, Nührenberg TG.
Clin Res Cardiol. 2018 Jul 26.

Efficacy and safety of bivalirudin for percutaneous coronary intervention in acute coronary syndromes: a meta-analysis of randomized-controlled trials.
Nührenberg TG, Hochholzer W, Mashayekhi K, Ferenc M, Neumann FJ.
Clin Res Cardiol. 2018 Sep;107(9):807-815.  

Impact of Reticulated Platelets on the Antiplatelet Effect of the Intravenous P2Y12-Receptor Inhibitor Cangrelor.
Stratz C, Nührenberg T, Valina CM, Löffelhardt N, Mashayekhi K, Ferenc M, Trenk D, Neumann FJ, Hochholzer W.
Thromb Haemost. 2018 Feb;118(2):362-368.

Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo.
Gilsbach R, Schwaderer M, Preissl S, Grüning BA, Kranzhöfer D, Schneider P, Nührenberg TG, Mulero-Navarro S, Weichenhan D, Braun C, Dreßen M, Jacobs AR, Lahm H, Doenst T, Backofen R, Krane M, Gelb BD, Hein L.
Nat Commun. 2018 Jan 26;9(1):391.

Alteration of von Willebrand Factor after Transcatheter Aortic Valve Replacement in the Absence of Paravalvular Regurgitation.
Pawlitschek F, Keyl C, Zieger B, Budde U, Beyersdorf F, Neumann FJ, Stratz C, Nührenberg TG, Trenk D. Thromb Haemost. 2018 Jan;118(1):103-111.

2017

DNA methylation signatures follow preformed chromatin compartments in cardiac myocytes.
Nothjunge S, Nührenberg TG, Grüning BA, Doppler SA, Preissl S, Schwaderer M, Rommel C, Krane M, Hein L, Gilsbach R.
Nat Commun. 2017 Nov 21;8(1):1667.

Impact of multi-vessel versus single-vessel disease on outcomes after percutaneous coronary interventions for chronic total occlusions.
Toma A, Stähli BE, Gick M, Gebhard C, Nührenberg T, Mashayekhi K, Ferenc M, Neumann FJ, Buettner HJ.
Clin Res Cardiol. 2017 Jun;106(6):428-435.

2016

5'-Hydroxymethylcytosine Precedes Loss of CpG Methylation in Enhancers and Genes Undergoing Activation in Cardiomyocyte Maturation.  
Kranzhöfer DK, Gilsbach R, Grüning BA, Backofen R, Nührenberg TG*, Hein L*.
PLoS One. 2016 Nov 16;11(11):e0166575. *shared last authorship.

Impact of reticulated platelets on antiplatelet response to thienopyridines is independent of platelet turnover.
Stratz C, Nührenberg T, Amann M, Cederqvist M, Kleiner P, Valina CM, Trenk D, Neumann FJ, Hochholzer W.
Thromb Haemost. 2016 Oct 28;116(5):941-948.

Comparison of Immature Platelet Count to Established Predictors of Platelet Reactivity During Thienopyridine Therapy.
Stratz C, Bömicke T, Younas I, Kittel A, Amann M, Valina CM, Nührenberg T, Trenk D, Neumann FJ, Hochholzer W.
J Am Coll Cardiol. 2016 Jul 19;68(3):286-293.

2015

Temporal variability in the antiplatelet effects of clopidogrel and aspirin after elective drug-eluting stent implantation. An ADAPT-DES substudy.
Nührenberg TG, Stratz C, Leggewie S, Hochholzer W, Valina CM, Gick M, Kirtane AJ, Stone GW, Neumann FJ, Trenk D.
Thromb Haemost. 2015 Nov;114(5):1020-7.

Large platelets but not putative endothelial progenitor cells are associated with low strut coverage after drug-eluting stent implantation.
Nührenberg TG, Zhao M, Stratz C, Amann M, Valina CM, Gick M, Trenk D, Binder H, Büttner HJ, Neumann FJ.
Int J Cardiol. 2015 Nov 15;199:358-65.

Cardiac Myocyte De Novo DNA Methyltransferases 3a/3b Are Dispensable for Cardiac Function and Remodeling after Chronic Pressure Overload in Mice.
Nührenberg TG*, Hammann N*, Schnick T, Preißl S, Witten A, Stoll M, Gilsbach R, Neumann FJ, Hein L.
PLoS One. 2015 Jun 22;10(6):e0131019. *shared first authorship

Intrinsic platelet reactivity before start with clopidogrel as predictor for on-clopidogrel platelet function and long-term clinical outcome.
Hochholzer W, Valina CM, Bömicke T, Amann M, Stratz C, Nührenberg T, Trenk D, Neumann FJ.
Thromb Haemost. 2015 Jul;114(1):109-14.

2014

Clinical pharmacology of current antiplatelet drugs.
Trenk D, Nührenberg T, Stratz C, Valina CM, Hochholzer W.
Herz. 2014 Nov;39(7):790-7.

Epigenetics in cardiac development, function, and disease.
Nührenberg T, Gilsbach R, Preissl S, Schnick T, Hein L.
Cell Tissue Res. 2014 Jun;356(3):585-600.

Controlled type II diabetes mellitus has no major influence on platelet micro-RNA expression. Results from micro-array profiling in a cohort of 60 patients.
Stratz C, Nührenberg T, Fiebich BL, Amann M, Kumar A, Binder H, Hoffmann I, Valina C, Hochholzer W, Trenk D, Neumann FJ.
Thromb Haemost. 2014 May 5;111(5):902-11.

Purulent pericarditis and pneumonia caused by Streptococcus equi subsp. zooepidemicus.
Held J, Schmitz R, van der Linden M, Nührenberg T, Häcker G, Neumann FJ.
J Med Microbiol. 2014 Feb;63(Pt 2):313-6.

Arbeitsgruppenleiter und Ansprechpartner

Dr. med. Thomas Nührenberg

E-Mail: thomas.nuehrenberg@universitaets-herzzentrum.de

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