title: Deletion of the alpha8 integrin gene does not protect mice from myocardial fibrosis in DOCA hypertension.
abstract: BACKGROUND
  In the heart, the alpha8 integrin chain is expressed in fibroblasts and vascular smooth-muscle cells but its functional role in the myocardium is unknown. Integrins can contribute to tissue fibrosis in several organs. We tested the hypothesis that alpha8 integrin-mediated cell-matrix interactions add to cardiac fibrotic alterations during hypertension.
  
  
  METHODS
  Desoxycorticosterone-acetate (DOCA)-salt hypertension was induced in mice homozygous for a deletion of the alpha8 integrin chain and wild-type mice. Histological and immunohistochemical evaluations were performed in heart tissue.
  
  
  RESULTS
  Blood pressure was slightly higher in DOCA-treated alpha8 integrin-deficient mice compared to DOCA-treated wild types. Expression of alpha8 integrin and its ligands fibronectin and osteopontin was increased in the hearts of DOCA-treated wild types compared to salt-loaded controls. However, relative left ventricular weights did not differ between DOCA-treated wild types and alpha8 integrin-deficient mice. Moreover, expansion of collagen I immunoreactivity and cell proliferation was similar in both groups. The number of osteopontin-positive cells was not different in DOCA-treated alpha8 integrin-deficient and DOCA-treated wild-type mice. Despite of a comparable degree of fibrosis in both groups, alpha-smooth-muscle actin and discoidin domain receptor 2 (DDR2)-positive myofibroblasts were only detected in wild-type DOCA-treated mice, not in DOCA-treated alpha8 integrin-deficient mice.
  
  
  CONCLUSIONS
  The results show that lack of alpha8 integrin does not reduce fibrotic changes in the hearts of DOCA-salt hypertensive mice. Our findings do not argue for a profibrotic effect of an increased alpha8 integrin expression in the myocardium in hypertension.
authors.affiliation: Department of Pediatric and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen, Germany. andrea.hartner@uk-erlangen.de
authors.forename: Andrea
authors.initials: A
authors.lastname: Hartner
authors.forename: Nada
authors.initials: N
authors.lastname: Cordasic
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rascher
authors.forename: Karl F
authors.initials: KF
authors.lastname: Hilgers
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004247:DNA / Q000235:genetics*; D003900:Desoxycorticosterone / Q000633:toxicity; D004195:Disease Models, Animal; D004719:Endomyocardial Fibrosis / Q000097:blood / Q000209:etiology / Q000235:genetics*; D015870:Gene Expression; D006973:Hypertension / Q000097:blood / Q000139:chemically induced / Q000150:complications*; D007150:Immunohistochemistry; D039001:Integrin alpha Chains / Q000097:blood / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion
chemical_list: D039001:Integrin alpha Chains; C093856:integrin alpha8; D003900:Desoxycorticosterone; D004247:DNA