Early sequence of cardiac adaptations and growth factor formation in pressure- and volume-overload hypertrophy.
To investigate the time sequence of cardiac growth factor formation, echocardiographic and hemodynamic measurements were performed at scheduled times, and mRNAs for angiotensinogen, prepro-endothelin-1 (ppET-1), and insulin-like growth factor I (IGF-I) were quantified with RT-PCR and localized with in situ hybridization in pigs (fluothane anesthesia) by use of pressure or volume overload (aortic banding and aorta-cava fistula, respectively). Relative peptide formation was also measured by radioimmunoassay. In pressure overload, angiotensinogen and ppET-1 mRNA overexpression on myocytes (13 times vs. sham at 3 h and 112 times at 6 h, respectively) was followed by recovery (12 h) of initially decreased (0.5-6 h) myocardial contractility. In volume overload, contractility was not decreased, the angiotensinogen gene was slightly upregulated at 6 h (6.7 times), and ppET-1 was not overexpressed. IGF-I mRNA was overexpressed on myocytes (at 24 h) in both volume and pressure overload (14 times and 37 times, respectively). In the latter setting, a second ppET-1 overexpression was detectable on myocytes at 7 days. In conclusion, acute cardiac adaptation responses involve different growth factor activation over time in pressure versus volume overload; growth factors initially support myocardial contractility and thereafter induce myocardial hypertrophy.
Modesti
P A
PA
Clinica Medica Generale e Cardiologia, University of Florence, 50134 Florence, Italy.
Vanni
S
S
Bertolozzi
I
I
Cecioni
I
I
Polidori
G
G
Paniccia
R
R
Bandinelli
B
B
Perna
A
A
Liguori
P
P
Boddi
M
M
Galanti
G
G
Serneri
G G
GG
D000222:Adaptation, Physiological; D000804:Angiotensin II / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001794:Blood Pressure; D002306:Cardiac Volume; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004452:Echocardiography; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006439:Hemodynamics; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine
D019332:Endothelin-1; D012333:RNA, Messenger; D000804:Angiotensin II; D007334:Insulin-Like Growth Factor I