The monocyte response to acute myocardial infarction- dynamic changes in monocyte gene expression -

• Applicant: Professor Dr. Hendrik Sager
• Subject Area: Cardiology, Angiology
• Term: from 2012 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 214414803

• Final Report Year: 2015

Final Report Abstract

In summary, we report how chronic stress interferes with hematopoiesis and describe interactions between the central nervous system, immunity and atherosclerosis. In mice exposed to stress, increased sympathetic nervous system activity decreased CXCL12 expression in the hematopoietic stem cell niche, accelerated HSC proliferation and enhanced neutrophil and monocyte production. These events caused extensive release of inflammatory leukocytes into the circulation and promoted plaque inflammation. Administration of a β3-adrenergic receptor blocker limited disease progression, supporting the notion that sympathetic nervous system signaling via this receptor and targeting of the CXCL12-CXCR4 interaction in the bone marrow should be explored as potential therapeutic avenues.

Publications

• Chronic variable stress activates hematopoietic stem cells. Nat Med. 2014 Jul;20(7):754-8. Epub 2014 Jun 22
  Heidt T, Sager HB, Courties G, Dutta P, Iwamoto Y, Zaltsman A, von Zur Muhlen C, Bode C, Fricchione GL, Denninger J, Lin CP, Vinegoni C, Libby P, Swirski FK, Weissleder R, Nahrendorf M
  
• Differential contribution of monocytes to heart macrophages in steady-state and after myocardial infarction. Circ Res. 2014 Jul 7;115(2):284-95. Epub 2014 May 1

  Heidt T, Courties G, Dutta P, Sager HB, Sebas M, Iwamoto Y, Sun Y, Da Silva N, Panizzi P, van der Laan AM, Swirski FK, Weissleder R, Nahrendorf M
  
• In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight. Nat Nanotechnol. 2014 Aug;9(8):648-55. Epub 2014 May 11
  Dahlman JE, Barnes C, Khan OF, Thiriot A, Jhunjunwala S, Shaw TE, Xing Y, Sager HB, Sahay G, Speciner L, Bader A, Bogorad RL, Yin H, Racie T, Dong Y, Jiang S, Seedorf D, Dave A, Singh Sandhu K, Webber MJ, Novobrantseva T, Ruda VM, Lytton-Jean AK, Levins CG, Kalish B, Mudge DK, Perez M, Abezgauz L, Dutta P, Smith L, Charisse K, Kieran MW, Fitzgerald K, Nahrendorf M, Danino D, Tuder RM, von Andrian UH, Akinc A, Panigrahy D, Schroeder A, Koteliansky V, Langer R, Anderson DG
  
• Ischemic stroke activates hematopoietic bone marrow stem cells. Circ Res. 2015 Jan 30;116(3):407-17. Epub 2014 Oct 31
  Courties G, Herisson F, Sager HB, Heidt T, Ye Y, Wei Y, Sun Y, Severe N, Dutta P, Scharff J, Scadden DT, Weissleder R, Swirski FK, Moskowitz MA, Nahrendorf M
  
• Macrophages retain hematopoietic stem cells in the spleen via VCAM-1. J Exp Med. 2015 Apr 6;212(4):497-512. Epub 2015 Mar 23
  Dutta P, Hoyer FF, Grigoryeva LS, Sager HB, Leuschner F, Courties G, Borodovsky A, Novobrantseva T, Ruda VM, Fitzgerald K, Iwamoto Y, Wojtkiewicz G, Sun Y, Da Silva N, Libby P, Anderson DG, Swirski FK, Weissleder R, Nahrendorf M
  
• Myocardial Infarction Activates CCR2(+) Hematopoietic Stem and Progenitor Cells. Cell Stem Cell. 2015 May 7;16(5):477-87
  Dutta P, Sager HB, Stengel KR, Naxerova K, Courties G, Saez B, Silberstein L, Heidt T, Sebas M, Sun Y, Wojtkiewicz G, Feruglio PF, King K, Baker JN, van der Laan AM, Borodovsky A, Fitzgerald K, Hulsmans M, Hoyer F, Iwamoto Y, Vinegoni C, Brown D, Di Carli M, Libby P, Hiebert SW, Scadden DT, Swirski FK, Weissleder R, Nahrendorf M