Research Topics

The bone marrow-heart interface

General scientific objectives:

Inflammation is a key driver of atherosclerosis and post-ischemic heart failure. The bone marrow niche controls hemotopoietic stem cell maintenace and mobilization. In collaboration with the Departments of Hematology and Cardiology, we study the interplay between cardiovascular diseases, the bone marrow1 stem cell niche and inflammation. The recent discovery that clonal hematopoiesis of indeterminate potential (CHIP), which refers to the selective expansion of mutated hematopoietic cells, is associated with a high incidence of coronary artery disease, raises many important questions and potential therapeutic options. Here we study the impact of CHIP on prognosis of patients with cardiovascular and lung disease and aim to identify specific mutations having a potential causal impact on disease progression.

Dr. Jedrzej Hoffmann, Tina Rasper

Dr. Yosif Manavski

Dr. Sebastian Cremer

References

  1. Aicher A, Heeschen C, Mildner-Rihm C, et al. Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med. 2003;9(11):1370-1376.
  2. Upcoming JAMA Cardiology paper

·         Assmus B1, Iwasaki M, Schächinger V, Roexe T, Koyanagi M, Iekushi K, Xu Q, Tonn T, Seifried E, Liebner S, Kranert WT, Grünwald F, Dimmeler S, Zeiher AM. Acute myocardial infarction activates progenitor cells and increases Wnt signalling in the bone marrow. Eur Heart J. 2012 Aug;33(15):1911-9

·         Kissel CK, Lehmann R, Assmus B, Aicher A, Honold J, Fischer-Rasokat U, Heeschen C, Spyridopoulos I, Dimmeler S, Zeiher AM. Selective functional exhaustion of hematopoietic progenitor cells in the bone marrow of patients with postinfarction heart failure. J Am Coll Cardiol. 2007 Jun 19;49(24):2341-9

·         Leistner DM, Seeger FH, Fischer A, Röxe T, Klotsche J, Iekushi K, Seeger T, Assmus B, Honold J, Karakas M, Badenhoop K, Frantz S, Dimmeler S, Zeiher AM. Elevated levels of the mediator of catabolic bone remodeling RANKL in the bone marrow environment link chronic heart failure with osteoporosis. Circ Heart Fail. 2012 Nov;5(6):769-77