title: Deficiency of actinin-associated LIM protein alters regional right ventricular function and hypertrophic remodeling.
abstract: Targeted deletion of actinin-associated LIM protein (ALP) in mice leads to right ventricular (RV) dysplasia and a mild RV cardiomyopathy. Although the phenotype has been thoroughly characterized, the mechanisms leading from the cytoskeletal defect to the disease are unclear. We hypothesized that ALP deficiency may be associated with (1) changes in regional systolic dysfunction and (2) regional dysregulation of hypertrophic growth, in accordance with the restricted expression of ALP in the outflow tract of the RV. We examined RV regional epicardial systolic strains with respect to end-diastole in ALP knockout (ALPKO) mice and wild-type controls using an open-chest preparation. Strain components were consistently lower in the ALPKO mice than wild-type controls (second principal strain E2: p = 0.05). RV pressure was slightly but not significantly lower in ALPKO mice as well. To assess regional growth, geometric remodeling was analyzed in ALPKO and wild-type mice after 4 weeks of chronic hypoxia (11% oxygen). The average amount of RV wall thickening in response to hypoxia was reduced to 11% in the ALPKO mice compared with 44% in the wild-type controls. In summary, the results are consistent with the view that disruption of ALP is associated with diminished RV contractile function as well as altered hypertrophic remodeling.
authors.affiliation: Department of Bioengineering, University of California San Diego, 9500 Gilman Dr., La Jolla 92093, CA, USA.
authors.forename: Ilka
authors.initials: I
authors.lastname: Lorenzen-Schmidt
authors.forename: Andrew D
authors.initials: AD
authors.lastname: McCulloch
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Omens
mesh_terms: D000818:Animals; D009202:Cardiomyopathies; D006321:Heart / Q000503:physiopathology; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology*; D006984:Hypertrophy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D060588:LIM Domain Proteins; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000172:deficiency*; D009206:Myocardium / Q000473:pathology; D018497:Ventricular Dysfunction, Right / Q000473:pathology / Q000503:physiopathology*; D020257:Ventricular Remodeling / Q000235:genetics
chemical_list: D060588:LIM Domain Proteins; D008840:Microfilament Proteins; C484642:Pdlim3 protein, mouse