Nuclear hypertrophy reflects increased biosynthetic activities in myocytes of human hypertrophic hearts.
BACKGROUND
The nucleus of the myocytes in human hypertrophic hearts is characterized by its bizarre shape and widespread clumping of chromatin. The functional significance has not been determined.


RESULTS
Left ventricular (LV) endomyocardial biopsies obtained from patients with dilated cardiomyopathy (DCM, n=23), postmyocarditis (n=13), hypertrophic cardiomyopathy (HCM, n=21), apical hypertrophic cardiomyopathy (APH, n=11) and hypertensive heart disease (HHD, n=11), and from nonhypertrophic hearts (controls, n=14) were examined. Myocyte size and LV mass index were similar among the hypertrophic hearts, but the nuclear hypertrophy score (grade 0-3) was highest in hearts with systolic failure (DCM and postmyocarditis) and higher in those without it (HCM, APH, and HHD), compared with controls. So were biosynthetic activities such as DNA repair/synthesis, immunohistochemically assessed by proliferating cell nuclear antigen, transcription activity by spliceosome component of 35 kDa, and translation efficiency by 70 kDa S6 protein kinase. There were significant correlations between nuclear hypertrophy and each biosynthetic activity. Additionally, most of the proliferating cell nuclear antigen-positive nuclei co-expressed oxidative DNA damage markers.


CONCLUSIONS
A link is suggested between structural alteration and molecular biological events in the nuclei of myocytes from human hypertrophic hearts; the nuclear hypertrophy reflects increased biosynthetic activities of DNA repair/synthesis, transcription, and translation efficiency.
Koda
Masahiko
M
Second Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan.
Takemura
Genzou
G
Okada
Hideshi
H
Kanoh
Motoo
M
Maruyama
Rumi
R
Esaki
Masayasu
M
Li
Yiwen
Y
Miyata
Shusaku
S
Kanamori
Hiromitsu
H
Li
Longhu
L
Ogino
Atsushi
A
Kondo
Takehito
T
Minatoguchi
Shinya
S
Fujiwara
Takako
T
Fujiwara
Hisayoshi
H
D000368:Aged; D002311:Cardiomyopathy, Dilated / Q000378:metabolism / Q000473:pathology*; D002843:Chromatin / Q000378:metabolism / Q000648:ultrastructure*; D004247:DNA / Q000096:biosynthesis; D004260:DNA Repair; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009205:Myocarditis / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000648:ultrastructure*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D014176:Protein Biosynthesis; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D017381:Spliceosomes / Q000378:metabolism; D014158:Transcription, Genetic
D002843:Chromatin; D018809:Proliferating Cell Nuclear Antigen; D004247:DNA; D019893:Ribosomal Protein S6 Kinases