title: Left ventricular dysfunction in murine models of heart failure and in failing human heart is associated with a selective decrease in the expression of caveolin-3.
abstract: BACKGROUND
  Caveolins are scaffolding proteins that are integral components of caveolae, flask-shaped invaginations in the membranes of all mammalian cells. Caveolin-1 and -2 are expressed ubiquitously, whereas caveolin-3 is found only in muscle. The role of caveolin-3 in heart muscle disease is controversial.
  
  
  RESULTS
  The present study was undertaken to assess the effects of left ventricular dysfunction on the expression of caveolin proteins using 2 well characterized models of murine heart failure and failing human heart. Transgenic mice with constitutive overexpression of A(1)-adenosine receptor (A(1)-TG) demonstrated cardiac dilatation and decreased left ventricular function at 10 weeks of age. This was accompanied by a marked decrease in caveolin-3 mRNA and protein levels compared with non-TG control mice. The change in caveolin-3 expression was selective, because levels of caveolin-1 and -2 did not change. Confocal imaging of myocytes isolated from A(1)-TG mice demonstrated a loss of the plate-like appearance of T tubules. Caveolin-3 levels were also reduced in hearts from mice overexpressing tumor necrosis factor α. There was a direct relationship between caveolin-3 expression and fractional shortening in all mice that were studied (r = 0.65; P < .001). Although we could not demonstrate a significant decrease in caveolin-3 levels in failing human heart, we did find a direct correlation (r = 0.7; P < .05) between levels of caveolin-3 protein and Ca(2+)-adenosine triphosphatase, a marker of the heart failure phenotype.
  
  
  CONCLUSIONS
  These results suggest a relationship between left ventricular dysfunction and caveolin-3 levels and suggest that caveolin-3 may provide a novel target for heart failure therapy.
authors.affiliation: Department of Medicine, Center for Translational Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Ellina Cheskis
authors.initials: EC
authors.lastname: Feiner
authors.forename: Paul
authors.initials: P
authors.lastname: Chung
authors.forename: Jean Francois
authors.initials: JF
authors.lastname: Jasmin
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Diana
authors.initials: D
authors.lastname: Whitaker-Menezes
authors.forename: Valerie
authors.initials: V
authors.lastname: Myers
authors.forename: Jianliang
authors.initials: J
authors.lastname: Song
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Feldman
authors.forename: Hajime
authors.initials: H
authors.lastname: Funakoshi
authors.forename: Brent R
authors.initials: BR
authors.lastname: Degeorge
authors.forename: Rao V
authors.initials: RV
authors.lastname: Yelamarty
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Koch
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
authors.forename: Charles F
authors.initials: CF
authors.lastname: McTiernan
authors.forename: Joseph Y
authors.initials: JY
authors.lastname: Cheung
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bristow
authors.forename: Tung O
authors.initials: TO
authors.lastname: Chan
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Feldman
mesh_terms: D000818:Animals; D051244:Caveolin 3 / Q000096:biosynthesis*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018487:Ventricular Dysfunction, Left / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D051244:Caveolin 3