title: Knockout of beta(1)- and beta(2)-adrenoceptors attenuates pressure overload-induced cardiac hypertrophy and fibrosis.
abstract: OBJECTIVE
  The role of beta-adrenoceptors in heart disease remains controversial. Although beta-blockers ameliorate the progression of heart disease, the mechanism remains undefined. We investigated the effect of beta-adrenoceptors on cardiac hypertrophic growth using beta(1)- and beta(2)-adrenoreceptor knockout and wild-type (WT) mice.
  
  
  METHODS
  Mice were subjected to aortic banding or sham surgery, and their cardiac function was determined by echocardiography and micromanometry.
  
  
  RESULTS
  At 4 and 12 weeks after aortic banding, the left ventricle:body mass ratio was increased by 80-87% in wild-type mice, but only by 15% in knockouts, relative to sham-operated groups. Despite the blunted hypertrophic growth, ventricular function in knockouts was maintained. WT mice responded to pressure overload with up-regulation of gene expression of inflammatory cytokines and fibrogenic growth factors, and with severe cardiac fibrosis. All these effects were absent in the knockout animals.
  
  
  CONCLUSIONS
  Our findings of a markedly attenuated cardiac hypertrophy and fibrosis following pressure overload in this knockout model emphasize that beta-adrenoceptor signalling plays a central role in cardiac hypertrophy and maladaptation following pressure overload.
authors.affiliation: Department of Experimental Cardiology, Baker Heart Research Institute, Melbourne, Victoria, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Kiriazis
authors.forename: K
authors.initials: K
authors.lastname: Wang
authors.forename: Q
authors.initials: Q
authors.lastname: Xu
authors.forename: X-M
authors.initials: XM
authors.lastname: Gao
authors.forename: Z
authors.initials: Z
authors.lastname: Ming
authors.forename: Y
authors.initials: Y
authors.lastname: Su
authors.forename: X-L
authors.initials: XL
authors.lastname: Moore
authors.forename: G
authors.initials: G
authors.lastname: Lambert
authors.forename: M E
authors.initials: ME
authors.lastname: Gibbs
authors.forename: A M
authors.initials: AM
authors.lastname: Dart
authors.forename: X-J
authors.initials: XJ
authors.lastname: Du
mesh_terms: D000222:Adaptation, Physiological; D000804:Angiotensin II; D000818:Animals; D001011:Aorta / Q000601:surgery; D001794:Blood Pressure; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D005786:Gene Expression Regulation; D005838:Genotype; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D010641:Phenotype; D018342:Receptors, Adrenergic, beta-1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors; D016277:Ventricular Function, Left / Q000235:genetics
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D000804:Angiotensin II