title: Antagonist of C5aR prevents cardiac remodeling in angiotensin II-induced hypertension.
abstract: BACKGROUND
  Inflammatory responses mediate the development of perivascular fibrosis and heart dysfunction induced by hypertension. Complement is an important inflammatory system, and we aimed to evaluate the effect of a specific C5a receptor antagonist (C5aRA), PMX53, on inflammation and perivascular fibrosis in the hypertensive heart of the mouse.
  
  
  METHODS
  Hypertension was induced by angiotensin II (Ang II) subcutaneously infused at a dose of 1500 ng/kg/min for 7 days. PMX53 was administrated at a dose of 1mg/kg, intraperitoneally 1 day before and daily during Ang II infusion.
  
  
  RESULTS
  Although C5aRA treatment did not affect the elevated blood pressure by Ang II infusion, it reduced cardiomyocyte hypertrophy, cardiac inflammation, and perivascular fibrosis. The mRNA and protein levels of the profibrotic cytokines transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF), as measured by real-time polymerase chain reaction and immunohistochemistry staining, were also attenuated by C5aRA treatment after Ang II infusion.
  
  
  CONCLUSIONS
  Our data suggest that inhibition of C5aR could be a potential therapeutic strategy in preventing organ damage in Ang II-induced hypertension.
authors.affiliation: Beijing AnZhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Zhang
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Wang
authors.forename: Yina
authors.initials: Y
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Du
mesh_terms: D000804:Angiotensin II; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D044087:Receptor, Anaphylatoxin C5a / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: C438957:AcPhe(ornithine-Pro-cyclohexylamine-Trp-Arg); C526318:CCN2 protein, mouse; D002317:Cardiovascular Agents; D016207:Cytokines; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D044087:Receptor, Anaphylatoxin C5a; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D055513:Connective Tissue Growth Factor; D003094:Collagen
keywords: blood pressure; cardiovascular damage; complement; hypertension; inflammation.