title: Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunction without affecting blood pressure in angiotensin II-high salt-induced hypertension.
abstract: OBJECTIVE
  Inflammation has been proposed as a key component in the development of hypertension and cardiac remodeling associated with different cardiovascular diseases. However, the role of the proinflammatory cytokine interleukin-6 in the chronic stage of hypertension is not well defined. Here, we tested the hypothesis that deletion of interleukin-6 protects against the development of hypertension, cardiac inflammation, fibrosis, remodeling and dysfunction induced by high salt diet and angiotensin II (Ang II).
  
  
  METHODS
  Male C57BL/6J and interleukin-6-knock out (KO) mice were implanted with telemetry devices for blood pressure (BP) measurements, fed a 4% NaCl diet, and infused with either vehicle or Ang II (90 ng/min per mouse subcutaneously) for 8 weeks. We studied BP and cardiac function by echocardiography at baseline, 4 and 8 weeks.
  
  
  RESULTS
  Myocyte cross-sectional area (MCSA), macrophage infiltration, and myocardial fibrosis were also assessed. BP increased similarly in both strains when treated with Ang II and high salt (Ang II-high salt); however, C57BL/6J mice developed a more severe decrease in left ventricle ejection fraction, fibrosis, and macrophage infiltration compared with interleukin-6-KO mice. No differences between strains were observed in MCSA, capillary density and MCSA to capillary density ratio.
  
  
  CONCLUSIONS
  In conclusion, absence of interleukin -6 did not alter the development of Ang II-high salt-induced hypertension and cardiac hypertrophy, but it prevented the development of cardiac dysfunction, myocardial inflammation, and fibrosis. This indicates that interleukin-6 plays an important role in hypertensive heart damage but not in the development of hypertension.
authors.affiliation: aDepartment of Internal Medicine, Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Michigan bCardiovascular Pathophysiology Institute, University of Buenos Aires, Argentina cDepartment of Physiology dDepartment of Internal Medicine, Wayne State University eDepartment of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan, USA.
authors.forename: Germán E
authors.initials: GE
authors.lastname: González
authors.forename: Nour-Eddine
authors.initials: NE
authors.lastname: Rhaleb
authors.forename: Martin A
authors.initials: MA
authors.lastname: D'Ambrosio
authors.forename: Pablo
authors.initials: P
authors.lastname: Nakagawa
authors.forename: Yunhe
authors.initials: Y
authors.lastname: Liu
authors.forename: Pablo
authors.initials: P
authors.lastname: Leung
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Dai
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Yang
authors.forename: Edward L
authors.initials: EL
authors.lastname: Peterson
authors.forename: Oscar A
authors.initials: OA
authors.lastname: Carretero
mesh_terms: D000418:Albumins / Q000737:chemistry; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology; D006332:Cardiomegaly / Q000503:physiopathology; D004452:Echocardiography; D005355:Fibrosis / Q000503:physiopathology; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D007249:Inflammation / Q000150:complications; D015850:Interleukin-6 / Q000235:genetics* / Q000502:physiology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology; D010641:Phenotype; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*
chemical_list: D000418:Albumins; D015850:Interleukin-6; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II