title: Myocytes positive for in situ markers for DNA breaks in human hearts which are hypertrophic, but neither failed nor dilated: a manifestation of cardiac hypertrophy rather than failure.
abstract: The significance of DNA breaks reported in failing hearts is controversial, although they may suggest myocyte apoptosis and may thus be responsible for the progression of heart failure. This study attempted to check the validity of the in situ markers for DNA breaks for detecting myocyte death and to evaluate separately two factors, failure or hypertrophy, crucial for DNA breaks in pathological human hearts. In the autopsy study, myocytes showed positivity for in situ nick end-labelling (TUNEL) and of Taq and Pfu polymerase-based in situ ligation assays not only in dilated cardiomyopathy (DCM, n = 9) with failure, but also in hypertrophic cardiomyopathy (HCM, n = 8) and hypertensive heart disease (HHD, n = 4) without failure. There was a significant correlation between each in situ marker and heart weight. The incidence of TUNEL-positive myocytes always exceeded that seen in in situ ligation assays. In addition, there were significant correlations between the in situ markers and the expression of the proliferating cell nuclear antigen (PCNA) and of the spliceosome component of 35 kD (SC-35). Similarly, in the left ventricular biopsy study using 23 DCM, 21 HCM, 11 HHD, and 13 non-hypertrophic hearts, the incidence of the in situ markers showed significant correlations with the left ventricular mass index and myocyte size, but not with cardiac function and dilatation. Positivity of myocytes for in situ markers for DNA breaks, such as TUNEL and in situ ligation assays, may be an epiphenomenon accompanying cardiac hypertrophy, but not myocyte death in pathological human hearts.
authors.affiliation: Second Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Koda
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.forename: Motoo
authors.initials: M
authors.lastname: Kanoh
authors.forename: Kenji
authors.initials: K
authors.lastname: Hayakawa
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Kawase
authors.forename: Rumi
authors.initials: R
authors.lastname: Maruyama
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Li
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
authors.forename: Takako
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: D000328:Adult; D017209:Apoptosis; D001706:Biopsy; D006332:Cardiomegaly / Q000235:genetics / Q000473:pathology*; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000473:pathology; D003327:Coronary Disease / Q000235:genetics / Q000473:pathology*; D004249:DNA Damage / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D009929:Organ Size; D016133:Polymerase Chain Reaction / Q000379:methods
chemical_list: D005819:Genetic Markers