title: Mononuclear Phagocytes Are Dispensable for Cardiac Remodeling in Established Pressure-Overload Heart Failure.
abstract: BACKGROUND
  Although cardiac and splenic mononuclear phagocytes (MPs), i.e., monocytes, macrophages and dendritic cells (DCs), are key contributors to cardiac remodeling after myocardial infarction, their role in pressure-overload remodeling is unclear. We tested the hypothesis that these immune cells are required for the progression of remodeling in pressure-overload heart failure (HF), and that MP depletion would ameliorate remodeling.
  
  
  RESULTS
  C57BL/6 mice were subjected to transverse aortic constriction (TAC) or sham operation, and assessed for alterations in MPs. As compared with sham, TAC mice exhibited expansion of circulating LyC6hi monocytes and pro-inflammatory CD206- cardiac macrophages early (1 w) after pressure-overload, prior to significant hypertrophy and systolic dysfunction, with subsequent resolution during chronic HF. In contrast, classical DCs were expanded in the heart in a biphasic manner, with peaks both early, analogous to macrophages, and late (8 w), during established HF. There was no significant expansion of circulating DCs, or Ly6C+ monocytes and DCs in the spleen. Periodic systemic MP depletion from 2 to 16 w after TAC in macrophage Fas-induced apoptosis (MaFIA) transgenic mice did not alter cardiac remodeling progression, nor did splenectomy in mice with established HF after TAC. Lastly, adoptive transfer of splenocytes from TAC HF mice into naïve recipients did not induce immediate or long-term cardiac dysfunction in recipient mice.
  
  
  CONCLUSIONS
  Mononuclear phagocytes populations expand in a phasic manner in the heart during pressure-overload. However, they are dispensable for the progression of remodeling and failure once significant hypertrophy is evident and blood monocytosis has normalized.
authors.affiliation: Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, United States of America.|Comprehensive Cardiovascular Center, University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Bindiya
authors.initials: B
authors.lastname: Patel
authors.affiliation: Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, United States of America.|Comprehensive Cardiovascular Center, University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Mohamed Ameen
authors.initials: MA
authors.lastname: Ismahil
authors.affiliation: Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, United States of America.|Comprehensive Cardiovascular Center, University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Tariq
authors.initials: T
authors.lastname: Hamid
authors.affiliation: Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, United States of America.|Comprehensive Cardiovascular Center, University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Bansal
authors.affiliation: Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, United States of America.|Comprehensive Cardiovascular Center, University of Alabama at Birmingham, Birmingham, AL, United States of America.|Medical Service, Birmingham VA Medical Center, Birmingham, AL, United States of America.
authors.forename: Sumanth D
authors.initials: SD
authors.lastname: Prabhu
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001011:Aorta / Q000276:immunology / Q000473:pathology; D002452:Cell Count; D003251:Constriction, Pathologic / Q000276:immunology / Q000473:pathology*; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology* / Q000637:transplantation; D004195:Disease Models, Animal; D018450:Disease Progression; D006333:Heart Failure / Q000276:immunology / Q000473:pathology*; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology* / Q000637:transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology / Q000473:pathology* / Q000637:transplantation; D011312:Pressure; D013154:Spleen / Q000276:immunology / Q000473:pathology; D020257:Ventricular Remodeling