Early expression of natriuretic peptides and SERCA in mild heart failure: association with severity of the disease.
BACKGROUND
We investigated changes in genetic expression of atrial and brain natriuretic peptides (ANP and BNP) and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) in patients with stable mild to moderate chronic heart failure (CHF), since data on this topic were primarily obtained in end-stage CHF.


METHODS
We studied tissue from 25 patients with idiopathic dilated cardiomyopathy (IDC) in New York Heart Association (NYHA) class II (n=12) and III-IV (n=13). Myocardial tissue from normal hearts (n=10) served as controls. Messenger RNA (mRNA) expression of ANP, BNP, and SERCA was isolated, and correlated with severity of CHF, left ventricular function (LVEF), peak oxygen uptake (peak VO(2)), and wedge pressure.


RESULTS
A significant trend for gradual changes in mRNA expression according to increasing NYHA class was found for ANP, BNP (P<0.0001) and SERCA (P=0.04), with a marked increase in patients with more advanced CHF (ANP and BNP: P<0.01 vs. controls; SERCA: NS) and less pronounced changes in patients with mild CHF. mRNA of ANP and BNP correlated strongly with LVEF (-0.621 and -0.621, respectively, both P<0.01) and peak VO(2) (-0.625 and -0.555, respectively, both P<0.01) and, to a lesser extent, with wedge pressure (0.440 and 0.488, respectively, both P<0.05). SERCA correlated most strongly with wedge pressure (-0.623, P<0.01), and weak, non-significant correlations with LVEF and peak VO(2) were found.


CONCLUSIONS
Genetic expression of ANP, BNP, and SERCA is progressively altered in proportion to the severity of CHF, although this is more marked for ANP and to a lesser extent BNP, than for SERCA. These changes support the concept that already early in CHF, genetic expression is affected, which has implications for the understanding of the pathophysiology of CHF.
Thoraxcenter, Department of Cardiology, University Hospital, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands. r.a.de.boer@thorax.azg.nl
R A
RA
de Boer
R H
RH
Henning
A J
AJ
Suurmeijer
Y M
YM
Pinto
E
E
Olthof
J H
JH
Kirkels
W H
WH
van Gilst
H J
HJ
Crijns
D J
DJ
van Veldhuisen
D000328:Adult; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002311:Cardiomyopathy, Dilated / Q000097:blood* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D012720:Severity of Illness Index
D012333:RNA, Messenger; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases