Age-related differences in the expression of proto-oncogene and contractile protein genes in response to pressure overload in the rat myocardium.
Cardiac adaptation to hemodynamic stress involves both quantitative (hypertrophy) and qualitative (pattern of gene expression) changes. Our previous studies have shown that advancing age in the rat is associated with diminished capacity to develop left ventricular hypertrophy in response to either ascending aortic constriction (AoC). In this study, we examined whether the expression of protooncogenes and contractile protein genes in response to AoC differs between adult (9-mo-old) and old (18-mo-old) rats. RNA was isolated from the left ventricles of AoC animals of both age groups subjected to a similar hemodynamic stress. Immediately after AoC, the levels of the ventricular expression of c-fos and c-jun protooncogenes were markedly lower in the old rats than in the adult animals. 5 d after the operation, the ratio of beta- to alpha-myosin heavy chain mRNAs increased significantly after AoC in both age groups. In contrast, AoC was associated with a marked reduction in the levels of mRNAs encoding sarcoplasmic reticulum Ca(2+)-ATPase (by 69%) and cardiac calsequestrin (by 49%) in the old rats but not in the adults. The mRNAs encoding atrial natriuretic factor and skeletal alpha-actin increased in response to AoC only in the adult rats. There were no significant differences in expression of the cardiac alpha-actin mRNA among the experimental groups. These data suggest that (a) the expression of protooncogenes in response to acute pressure overload is significantly reduced in the aged rats and (b) the pattern of expression of the contractile protein gene in response to AoC in the old rats differs qualitatively as well as quantitatively from that in younger animals. These age-related differences may play a role in the higher frequency of heart failure in the aged during hemodynamic stress.
Takahashi
T
T
Molecular Medicine Unit, Beth Israel Hospital, Boston, Massachusetts 02215.
Schunkert
H
H
Isoyama
S
S
Wei
J Y
JY
Nadal-Ginard
B
B
Grossman
W
W
Izumo
S
S
D000199:Actins / Q000235:genetics; D000367:Age Factors; D000818:Animals; D001011:Aorta / Q000503:physiopathology; D009320:Atrial Natriuretic Factor / Q000235:genetics; D000252:Calcium-Transporting ATPases / Q000235:genetics; D003285:Contractile Proteins / Q000235:genetics*; D015870:Gene Expression; D006333:Heart Failure / Q000378:metabolism; D006439:Hemodynamics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009218:Myosins / Q000235:genetics; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D014661:Vasoconstriction / Q000502:physiology
D000199:Actins; D003285:Contractile Proteins; D012333:RNA, Messenger; D009320:Atrial Natriuretic Factor; D009218:Myosins; D000252:Calcium-Transporting ATPases