title: Left ventricular hypertrophy in ascending aortic stenosis mice: anoikis and the progression to early failure.
abstract: BACKGROUND
  To determine potential mechanisms of the transition from hypertrophy to very early failure, we examined apoptosis in a model of ascending aortic stenosis (AS) in male FVB/n mice.
  
  
  RESULTS
  Compared with age-matched controls, 4-week and 7-week AS animals (n=12 to 16 per group) had increased ratios of left ventricular weight to body weight (4.7+/-0.7 versus 3.1+/-0.2 and 5. 7+/-0.4 versus 2.7+/-0.1 mg/g, respectively, P<0.05) with similar body weights. Myocyte width was also increased in 4-week and 7-week AS mice compared with controls (19.0+/-0.8 and 25.2+/-1.8 versus 14. 1+/-0.5 microm, respectively, P<0.01). By 7 weeks, AS myocytes displayed branching with distinct differences in intercalated disk size and staining for beta(1)-integrin on both cell surface and adjacent extracellular matrix. In vivo left ventricular systolic developed pressure per gram as well as endocardial fractional shortening were similar in 4-week AS and controls but depressed in 7-week AS mice. Myocyte apoptosis estimated by in situ nick end-labeling (TUNEL) was extremely rare in 4-week AS and control mice; however, a low prevalence of TUNEL-positive myocytes and DNA laddering were detected in 7-week AS mice. The specificity of TUNEL labeling was confirmed by in situ ligation of hairpin oligonucleotides.
  
  
  CONCLUSIONS
  Our findings indicate that myocyte apoptosis develops during the transition from hypertrophy to early failure in mice with chronic biomechanical stress and support the hypothesis that the disruption of normal myocyte anchorage to adjacent extracellular matrix and cells, a process called anoikis, may signal apoptosis.
authors.affiliation: Harvard-Thorndike Laboratory and the Department of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: B
authors.initials: B
authors.lastname: Ding
authors.forename: R L
authors.initials: RL
authors.lastname: Price
authors.forename: E C
authors.initials: EC
authors.lastname: Goldsmith
authors.forename: T K
authors.initials: TK
authors.lastname: Borg
authors.forename: X
authors.initials: X
authors.lastname: Yan
authors.forename: P S
authors.initials: PS
authors.lastname: Douglas
authors.forename: E O
authors.initials: EO
authors.lastname: Weinberg
authors.forename: J
authors.initials: J
authors.lastname: Bartunek
authors.forename: T
authors.initials: T
authors.lastname: Thielen
authors.forename: V V
authors.initials: VV
authors.lastname: Didenko
authors.forename: B H
authors.initials: BH
authors.lastname: Lorell
mesh_terms: D000818:Animals; D001024:Aortic Valve Stenosis / Q000150:complications*; D017209:Apoptosis / Q000502:physiology; D002303:Cardiac Output, Low / Q000209:etiology; D002450:Cell Communication / Q000502:physiology; D018450:Disease Progression; D004452:Echocardiography; D006439:Hemodynamics; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D019012:Integrin beta1 / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018613:Microscopy, Confocal; D014018:Tissue Distribution
chemical_list: D019012:Integrin beta1