A STUDY OF THE EXPRESSION OF THE SARCOPLA SMIC-RETICULUM CALCIUM-ATPASE GENE IN THE LEFT-VENTRICLE OF THE SHEEPS FETUS SUBMITTED TO CHRONICINCREASED AFTERLOAD IN-UTERO

The messenger RNA of the cardiac sarcoplasmic reticulum ATP-ase (SERCA -2a) increases in the left ventricle (LV) during ontogenic development but decreases in hypertrophy induced by increased afterload. Because of the frequency of increased left ventricular overload in congenital heart disease, the authors investigated to see if these increases were likely to interfere with the normal ontogenic program of expression o f the SERCA-2a gene in the LV of sheep's foetus. A preductal coarctati on of the aorta was realised by banding the transverse aorta (AoT) at 93 days' gestation in 9 foetus (CoA) matched with 9 healthy twin foetu s (T). All the foetus underwent haemodynamic, anatomical, histological and molecular biological investigations 4 weeks later. The concentrat ion of SERCA-2a mRNA in the LV was measured by hybridation of a Northe rn blot with a rat DNAc probe normalised with RNAr 18S. A coarctation was observed in all the CoA group and in none of the T. The ratio of L V weight/body weight was increased in 65 % of CoA (p <0.0001). The con centration of SERCA-2a mRNA in the LV was much reduced in CoA (average -28.6 %) of the values observed in T (p = 0.003). Left ventricular hy pertrophy of the sheep's foetus induced by pathological increases of a fterload surpassed or slowed down the physiological ontogenic maturati on of expression of the SERCA-2a gene in abnormalities of cardiac pump function.