Different growth factor activation between right and left ventricle in experimental volume overload

Cardiac overexpression of angiotensinogen (AGT) and insulin-like growth factor (IGF)-I genes has been reported in experimental volume overload. Different hemodynamic response to volume overload in left and right ventricles might influence the local expression of cardiac growth factors. Therefore we investigated AGT, IGF-I, and prepro endothelin (ppET)-1 mRNAs in right and left ventricles of 15 adult pigs (30+5 kg) after the creation of aorta-cava fistula distal to the renal arteries causing a 50% increase in cardiac output. Six animals were sham-operated. At baseline, 2 weeks, 1, 2 and 3 months after surgery hemodynamic and echocardiographic measurements were recorded. Animals were then euthanized and myocardial specimens were taken for RT-PCR studies. In the left ventricle volume overload did not cause significant changes in ventricular pressure and contractility (Vcf). RT-PCR revealed a selective overexpression of IGF-I mRNA at 2 weeks (2-fold) which remained elevated at following times in a close association to the increase in left ventricular mass (from 59±9 to 92±7 and 254±23 g at 2 weeks and 3 months respectively, p<0.05 for both). Conversely, in the right ventricle both systolic and end-diastolic pressure significantly increased at 2 weeks (p<0.05 vs baseline for both) and remained elevated vs baseline throughout the study. RT-PCR analysis showed overexpression of AGT and IGF-I mRNAs at 2 weeks (p<0.05 for both) and ppET-1 transcript at 1 month (24-fold). All genes remained overexpressed at the following experimental times (p<0.05). In conclusion: a differential pattern of growth factor response to volume overload is detectable in left and right ventricle: 1) AGT and ppET-1 mRNA expression are restricted to right ventricular myocardium which had to face both pressure and volume overload, 2) IGF-I gene is overexpressed in both ventricles independently on AGT gene activation 3) in left ventricle IGF-I expression is associated with marked hypertrophy without impairment of myocardial contractility.