1081 Poster Cat: Molecular and Cellular Cardiology, Basic Research
SILENCING OF CSF1R AND CSF1 IN MYELOID CELLS AMELIORATES EXPERIMENTAL AUTOIMMUNE MYOCARDITIS
S. Meyer1,2, M. Bohlender1, S. Werkmeister1, V. Eckstein3, H.A. Katus1,2,
F. Leuschner1,2
1. Department of Internal Medicine III, University of Heidelberg, Heidelberg, Germany 2. DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, Germany
3. Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
Background: Myocarditis is characterized by the infiltration of leukocytes into heart tissue and subsequent impairment of heart function. High leukocyte numbers in the inflamed heart correlate with poor prognosis. Monocytes are the predominant leukocytes at the site of inflammation and are thought to mediate further tissue damage. They develop from hematopoietic stem cells in a Colony Stimulating Factor (CSF1) dependent manner via several defined progenitor stages.
Objectives: We here sought to modulate the inflammatory response in murine experimental autoimmune myocarditis (EAM) through inhibition of monocyte development by silencing CSF1 and its receptor CD115.
Methods and Results: EAM was induced by injection of myosin-peptide in male BALB/C mice at the age of 8 weeks. Silencing of CSF1 and respectively its receptor CD115 by nanoparticle -encapsulated siRNA (siCSF1 and siCD115) started 14 days after induction of EAM. Injection of nanoparticles containing siRNA against Luciferase (siLuc) served as a control. FACS analysis revealed reduced monocyte-infiltration into heart tissue in animals receiving siCSF-1 or siCD115-nanoparticle therapy compared to the control group. Echocardiographic evaluation of heart function showed that siCSF1 and siCD115 nanoparticle therapy improve left ventricular ejection fraction compared to the control group. In addition, histological analysis of hearts demonstrated reduced fibrosis in both siCSF1 and siCD115 treated animals 60 days after induction of EAM.
Conclusion: We here show that in vivo silencing of CSF1 and CD115 effectively reduce the monocytic response in hearts of animals during acute autoimmune myocarditis thereby limiting tissue damage and preserving heart function.