title: Suppression of murine autoimmune myocarditis achieved with direct renin inhibition.
abstract: The renin angiotensin system (RAS) plays an important role in the pathogenesis of cardiovascular diseases and inflammation. Myocarditis is an inflammatory disease of the heart, and the role of the RAS in its pathophysiology is unknown. Because the direct renin inhibitor, aliskiren, is thought to block RAS completely, we investigated the cardioprotective effect of aliskiren in mice with experimental autoimmune myocarditis (EAM).
  
  
  
  A cardiac α-myosin heavy chain peptide was injected in mice on days 0 and 7. Aliskiren 25mg/kg per day (n=10) or vehicle (n=10) was administered to EAM mice starting on day 0 and the animals were killed on day 21.
  
  
  
  Aliskiren significantly prevented the progression of left ventricular wall thickening in EAM hearts compared to the vehicle-treated group. Histologically, the inflammatory cell infiltration and fibrosis area ratios in the aliskiren-treated group were lower than that in the vehicle-treated group. Immunohistochemistry revealed that aliskiren suppressed CD4 positive cell infiltration in EAM hearts compared to vehicle. Moreover, aliskiren decreased mRNA levels of interleukin (IL)-2, interferon-γ, tumor necrosis factor-α, and collagen 1. In vitro study showed that aliskiren inhibited T cell proliferation and IL-2 production induced by myosin stimulation.
  
  
  
  Our results suggest that aliskiren ameliorates EAM by suppressing T-cell activation and inflammatory cytokines, and has potential as a treatment for myocarditis.
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Takamura
authors.affiliation: Department of Advanced Clinical Science and Therapeutics, The University of Tokyo, Tokyo, Japan. Electronic address: junichisuzuki-circ@umin.ac.jp.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Suzuki
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Watanabe
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tada
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maejima
authors.affiliation: Department of Advanced Clinical Science and Therapeutics, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akazawa
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Isobe
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005650:Fumarates / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D020721:Nervous System Autoimmune Disease, Experimental / Q000188:drug therapy*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D016207:Cytokines; D005650:Fumarates; D012333:RNA, Messenger; D000092502:Renin Inhibitors; C446481:aliskiren
keywords: Cytokines; Inflammation; Myocarditis; Renin