cArbeitsgruppe | Dr. Christian Napp

Research Focus

In general, our group is interested in acute heart failure, from a clinical and basic scientific perspective. Acute heart failure is associated with a high burden of morbidity and mortality, and mechanisms behind this syndrome are still incompletely understood. Many aspects of acute heart failure warrant further research, such as diagnostic and prognostic biomarkers and regenerative strategies. As such, our group focuses on monocytes as effectors in tissue regeneration, mechanisms of angiogenesis as a central regenerative process and the Takotsubo Syndrome, a prototypical example of acute heart failure. We are further interested in non-compaction cardiomyopathy.

 

Effector Molecules of Monocytes

Monocytes are members of the innate immune system, historically being regarded as pro-inflammatory phagocytes. However, recent research indicates a central role of monocytes for regulation of tissue regeneration and homeostasis. Monocyte subsets, distinguished by Ly6c in mice and CD16 in man, seem to be responsible for the diverse functions of the monocytic cell pool. Several publications demonstrate a critical role especially of the Ly6clo (CD16+) subset for vascular regeneration. However, effector molecules mediating these processes are largely unknown. One project in the lab investigates changes in circulating monocyte subsets in patients, e.g. after myocardial infarction. Another project aims to identify molecules expressed by monocytes which may be responsible for their regenerative capacity.

 

Genes regulating angiogenesis

Another branch focuses on angiogenesis. Vascular growth is roughly divided into three parts: De novo embryonic angiogenesis, sprouting angiogenesis and arteriogenesis. Especially the knowlegde about sprouting angiogenesis has immensely been expanded by recent research, confirming that sprouting is a heavily regulated process throughout the mammalian system. Nearly all recent publications utilize the retina angiogenesis model and/or the translucent zebrafish. In a recent paper we could demonstrate a role of the Notch ligand Delta-like 1 during angiogenesis. From this and other projects we have broad experience with the retina angiogenesis model and offer it to other groups on a collaborative basis. In our own lab we currently characterize the role of the enzyme MAP-Kinase activated protein kinase 2 (MK2) during angiogenesis and arteriogenesis, but also during vascular adaptation in different disease models.

 

Takotsubo Syndrome

A more translational part is dedicated to the investigation of Takotsubo Syndrome, an acute heart failure syndrome which mechanism is still incompletely understood. We are part of the largest worldwide registry of Takotsubo patients, which analyzes features of the disease in a retrospective and prospective manner. By this were were able to show that the disease carries substantial risk in the acute phase.

 

Non-Compaction-Cardiomyopathy

Non-Compaction-Cardiomypathy (NCCM) is a probably congenital and in some cases inherited heart disease. It was only recently recognized and many aspects are poorly understood. It is characterized by a dual-layer composition of the myocardium, with a prominent non-compacted spongiform inner layer. NCCM may lead to severe heart failure, however in some affected individuals left ventricular function remains preserved. Typical complications comprise arrhythmia and/or thromboembolism. We aim to better characterize this special disease and we test novel imaging criteria and biomarkers for diagnosis and prognosis of NCCM.

 

Funding

HiLF (Hochschulinterne Leistungsförderung), Hannover Medical School Intramural funding

Awards

L. Christian Napp

  • 2011
    Rudi Busse Young Investigator Award for Experimental Cardiology, 1st place, Annual Meeting of the German Society for Cardiology, Mannheim, Germany

  • 2010
    Young Investigator Award, Annual Meeting of the German Society for Microcirculation and Vascular Biology, Berlin, Germany

  • 2010
    Poster Award, 1st place, Section “Angiology”, Annual Meeting of the German Society of Internal Medicine, Wiesbaden, Germany

  • 2009
    Rudi Busse Young Investigator Award for Experimental Cardiology, 2nd place, Annual Meeting of the German Society for Cardiology, Mannheim, Germany

  • 2007
    ATVB Merit Award for Young Investigators, Council on Arteriosclerosis, Thrombosis and Vascular Biology, American Heart Association, Scientific Sessions 2007, Orlando, Florida, USA.

Olga Jabs

  • 2013
    Young Investigator Travel Grant, German Society for Cardiology

Collaborations
  • PD Dr. U. Bavendiek, Hannover Medical School
  • Prof. Dr. Wouter H. Moolenaar, The Netherlands Cancer Institute, Amsterdam
  • PD Dr. Dr. C. Templin, University Hospital Zurich, Switzerland
  • Prof. Dr. Dr. T. Thum, Institute of Molecular and Translational Therapeutic Strategies, Hannover
  • Dr. J. Tongers, Hannover Medical School
  • Prof. Dr. K. C. Wollert, Hannover Medical School
Publications
  • Templin C, Ghadri JR, Napp LC. Takotsubo (Stress) Cardiomyopathy. N Engl J Med. 2015 Dec 31; 373(27):2689-91.

  • Napp LC, Kühn C, Hoeper MM, Vogel-Claussen J, Haverich A, Schäfer A, Bauersachs J. Cannulation strategies for percutaneous extracorporeal membrane oxygenation in adults. Clin Res Cardiol. 2015 Nov 25. [Epub ahead of print]

  • Thackeray JT, Derlin T, Haghikia A, Napp LC, Wang Y, Ross TL, Schäfer A, Tillmanns J, Wester HJ, Wollert KC, Bauersachs J, Bengel FM. Molecular Imaging of the Chemokine Receptor CXCR4 After Acute Myocardial Infarction. JACC Cardiovasc Imaging. 2015 Nov 5. [Epub ahead of print]

  • Limbourg A, von Felden J, Jagavelu K, Krishnasamy K, Napp LC, Kapopara PR, Gaestel M, Schieffer B, Bauersachs J, Limbourg FP, Bavendiek U. MAP-Kinase Activated Protein Kinase 2 Links Endothelial Activation and Monocyte/macrophage Recruitment in Arteriogenesis. PLoS One. 2015 Oct 2;10(10):e0138542.

  • Sieweke JT, Westhoff-Bleck M, Napp LC, Avsar M, Vogel-Claussen J, Schäfer A, Bauersachs J, Brehm M. Myocardial infarction in grown up patients with congenital heart disease: An emerging high-risk combination. Int J Cardiol. 2015 Oct 9;203:138-140.

  • Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M, Cammann VL, Sarcon A, Geyer V, Neumann CA, Seifert B, Hellermann J, Schwyzer M, Eisenhardt K, Jenewein J, Franke J, Katus HA, Burgdorf C, Schunkert H, Moeller C, Thiele H, Bauersachs J, Tschöpe C, Schultheiss HP, Laney CA, Rajan L, Michels G, Pfister R, Ukena C, Böhm M, Erbel R, Cuneo A, Kuck KH, Jacobshagen C, Hasenfuss G, Karakas M, Koenig W, Rottbauer W, Said SM, Braun-Dullaeus RC, Cuculi F, Banning A, Fischer TA, Vasankari T, Airaksinen KE, Fijalkowski M, Rynkiewicz A, Pawlak M, Opolski G, Dworakowski R, MacCarthy P, Kaiser C, Osswald S, Galiuto L, Crea F, Dichtl W, Franz WM, Empen K, Felix SB, Delmas C, Lairez O, Erne P, Bax JJ, Ford I, Ruschitzka F, Prasad A, Lüscher TF. Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy. N Engl J Med. 2015 Sep 3;373(10):929-38. doi: 10.1056/NEJMoa1406761.

  • Fraccarollo D, Galuppo P, Sieweke JT, Napp LC, Grobbecker P, Bauersachs J: Efficacy of mineralocorticoid receptor antagonism in the acute myocardial infarction phase: eplerenone versus spironolactone ESC Heart Failure. published online: 28 JUL 2015 | DOI: 10.1002/ehf2.12053

  • Napp LC, Ghadri JR, Cammann VL, Bauersachs J, Templin C. Takotsubo cardiomyopathy: Completely simple but not so easy. Int J Cardiol. 2015 Oct 15;197:257-9. Epub 2015 Jun 20.

  • Napp LC, Reinke T, Ius F, Schmitto JD, Haverich A, Bauersachs J. Consequences of ventricular tachyarrhythmia in patients with a left ventricular assist device: Live recording in the ICU. Acute Card Care. 2015 Jun;17(2):36-37.

  • Napp LC, Bauersachs J: Non-Compaction-Kardiomyopathie. Lehnert H (Hrsg.): DGIM Innere Medizin (Reihe: Springer Reference Medizin), 2015.

  • Napp LC, Bauersachs J: Takotsubo-Kardiomyopathie. Lehnert H (Hrsg.): DGIM Innere Medizin (Reihe: Springer Reference Medizin), 2015.

  • Napp LC, Ghadri JR, Bauersachs J, Templin C. Takotsubo cardiomyopathy - Everything's illuminated? Int J Cardiol. 2015 May 30;196:36-37. [Epub ahead of print]

  • Uribarri A, Rojas SV, Avsar M, Hanke JS, Napp LC, Berliner D, Bavendiek U, Bauersachs J, Bara C, Sanchez PL, Haverich A, Schmitto JD. First series of mechanical circulatory support in non-compaction cardiomyopathy: Is LVAD implantation a safe alternative? Int J Cardiol. 2015 Apr 7;197:128-132. doi: 10.1016/j.ijcard.2015.04.046. [Epub ahead of print]

  • Napp LC, Ghadri JR, Bauersachs J, Templin C. Acute coronary syndrome or Takotsubo cardiomyopathy: The suspect may not always be the culprit. Int J Cardiol. 2015 Mar 18;187:116-119. [Epub ahead of print]

  • Napp LC, Brehm M, Kühn C, Schäfer A, Bauersachs J. Heart against veno-arterial ECMO: Competition visualized. Int J Cardiol. 2015 Mar 21;187:164-165. [Epub ahead of print]

  • Korf-Klingebiel M, Reboll MR, Klede S, Brod T, Pich A, Polten F, Napp LC, Bauersachs J, Ganser A, Brinkmann E, Reimann I, Kempf T, Niessen HW, Mizrahi J, Schönfeld HJ, Iglesias A, Bobadilla M, Wang Y, Wollert KC. Myeloid-derived growth factor (C19orf10) mediates cardiac repair following myocardial infarction. Nat Med. 2015 Feb;21(2):140-9. Epub 2015 Jan 12.

  • Napp LC; Schatka I, Kempf T, Bavendiek U, Bengel FM, Bauersachs J. Single coronary artery anomaly with interarterial left main: caught inbetween. Eur Heart J 2014 Dec 29. pii: ehu495. [Epub ahead of print]

  • Kumarswamy R, Volkmann I, Beermann J, Napp LC, Jabs O, Bhayadia R, Melk A, Ucar A, Chowdhury K, Lorenzen JM, Gupta SK, Batkai S, Thum T. Vascular importance of the miR-212/132 cluster. Eur Heart J. 2014 Sep 12. [Epub ahead of print]

  • Kapopara PR, von Felden J, Soehnlein O, Wang Y, Napp LC, Sonnenschein K, Wollert KC, Schieffer B, Gaestel M, Bauersachs J, Bavendiek U. Deficiency of MAPK-activated protein kinase 2 (MK2) prevents adverse remodelling and promotes endothelial healing after arterial injury. Thromb Haemost. 2014 Aug 14;112(6). [Epub ahead of print]

  • Limbourg A, Schnabel S, Lozanovski VJ, Napp LC, Ha TC, Maetzig T, Bauersachs J, Naim HY, Schambach A, Limbourg FP. Genetic reporter analysis reveals an expandable reservoir of OCT4+ cells in adult skin. Cell Regen (Lond) 2014 Jun 14;3(1):9.

  • Napp LC, Templin C: What You See is What You Get? Imaging of Cell Therapy for Cardiac Regeneration. Curr Cardiovasc Imaging Rep January 2014, 7:9243

  • Napp LC, Bavendiek U, Tongers J, Bauersachs J, Roentgen P: Dynamic left ventricular outflow tract obstruction: Hemodynamic pitfall ahead. Acute Card Care 2013 Sep;15(3):76-7. Epub 2013 Aug 8.

  • Jaguszewski M, Osipova J, Ghadri JR, Napp LC, Widera C, Franke J, Fijalkowski M, Nowak R, Fijalkowska M, Volkmann I, Katus HA, Wollert KC, Bauersachs J, Erne P, Lüscher TF, Thum T, Templin C. A signature of circulating microRNAs differentiates takotsubo cardiomyopathy from acute myocardial infarction. Eur Heart J. 2013 Sep 17. [Epub ahead of print]

  • Napp LC, Baraki H, Kutschka I, Bredt M, Brehm MU, Bauersachs J, Bavendiek U: Dynamic obstruction of the left main coronary artery ostium by a papillary fibroelastoma. Cardiovasc Pathol 2013 Jul 15. Epub ahead of print.

  • Napp LC, Luesebrink U, Vogel-Claussen J, Bauersachs J, Roentgen P: Two’s company: Double chambered right ventricle. Circulation 2013 Mar 5;127(9):e469-70.

  • Napp LC*, Augustynik M*, Paesler F, Krishnasamy K, Woiterski J, Limbourg A, Bauersachs J, Drexler H, Le Noble F, Limbourg FP. Extrinsic Notch Ligand Delta-Like 1 Regulates Tip Cell Selection and Vascular Branching Morphogenesis. Circ Res. 2012 Feb 17;110(4):530-5. Epub 2012 Jan 26

  • Ucar A, Gupta SK, Fiedler J, Erikci E, Kardasinski M, Batkai S, Dangwal S, Kumarswamy R, Bang C, Holzmann A, Remke J, Caprio M, Jentzsch C, Engelhardt S, Geisendorf S, Glas C, Hofmann TG, Nessling M, Richter K, Schiffer M, Carrier L, Napp LC, Bauersachs J, Chowdhury K, Thum T. The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy. Nat Commun 2012 Sep 25;3:1078.

  • Kempf T, Zarbock A, Widera C, Butz S, Stadtmann A, Rossaint J, Bolomini-Vittori M, Korf-Klingebiel M, Napp LC, Hansen B, Kanwischer A, Bavendiek U, Beutel G, Hapke M, Sauer MG, Laudanna C, Hogg N, Vestweber D, Wollert KC. GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice. Nat Med 2011 May;17(5):581-8. Epub 2011 Apr 24.

  • Napp LC, Limbourg FP. Notch Signalling in Arteries: From Embryonic Development to Postnatal Homeostasis and Growth. Chapter 3, p. 39-65. In: Deindl E, Schaper W, eds. The Collateral Circulation - Molecular Regulation, Pathophysiology and Therapeutics I. [e-book]. Shaker Publishers; 2011.

  • Laurisch S, Jaedtke M, Demir R, Sorrentino SA, Kielstein JT, Rennekampff HO, Vogt PM, Meyer GP, Fuchs M, Klein G, Drexler H, Schieffer B, Napp LC. Allopurinol induced hypersensitivity syndrome resulting in death. Med Klinik 2010;105(4):262-6.

  • Limbourg A, Korff T, Napp LC, Schaper W, Drexler H, Limbourg FP. Evaluation of Postnatal Arteriogenesis and Angiogenesis in a Mouse Model of Hindlimb Ischemia. Nat Protoc 2009;4(12):1737-46.

  • Templin C, Grote K, Schledzewski K, Ghadri JR, Schnabel S, Napp LC, Schieffer B, Kurzen H, Goerdt S, Landmesser U, Koenen W, Faulhaber J: Ex vivo expanded hematopoietic progenitor cells improve dermal wound healing by paracrine mechanisms. Exp Dermatol 2009;18(5):445-53.

  • Napp LC, Drexler H: What are the clinical effects of bone marrow cell therapy in patients with severe coronary artery disease? Nat Clin Pract Cardiovasc Med 2008;5(7):362-3.

Group leader

Dr. L. Christian Napp
Tel.: 2246">0511 532-2246
Fax.: 0511 532-3357
napp.christian@mh-hannover.de

Leonie Bode
MD student
bode.leonie@mh-hannover.de

 

Olga Jabs
MD student | StrucMed fellow

olgajabs@gmx.de

 

Biniam Kiflai
MD student

biniam.1@hotmail.com

s