SELECTIVE CHANGES IN CARDIAC GENE-EXPRESSION DURING COMPENSATED HYPERTROPHY AND THE TRANSITION TO CARDIAC DECOMPENSATION IN RATS WITH CHRONIC AORTIC BANDING

Left ventricular hypertrophy (LVH) is associated with reinduction of t he fetal program of gene expression. It is unclear whether this patter n of cardiac gene expression changes with the development of left vent ricular decompensation and failure. To answer these questions, we quan tified steady-state levels of mRNA by the polymerase chain reaction in the left ventricular myocardium of rats 8 and 20 weeks after ascendin g aortic banding. Clinical and hemodynamic assessment identified two d istinct groups of animals 20 weeks after aortic banding. The first gro up (20-week nonfailed LVH) demonstrated substantial LVH but no depress ion in systolic developed pressure per gram left ventricular weight co mpared with the age-matched control group. In contrast, a second group of rats exhibited clinical signs of congestive failure as well as a m arked diminution in left ventricular developed pressure per gram. Asse ssment of the levels of mRNA encoding a panel of cardiac proteins demo nstrated a greater than twofold increase in beta-myosin heavy chain mR NA and an approximately sixfold increase in atrial natriuretic factor mRNA in left ventricular myocardium of all three groups (8-week LVH, 2 0-week nonfailed LVH, 20-week failed LVH) when compared with appropria te age-matched control groups. In contrast, Ca2+-ATPase mRNA levels we re decreased by 50% only in the left ventricular myocardium of animals with both clinical signs and hemodynamic indexes consistent with card iac decompensation (20-week failed LVH). These results suggest that in rats with ascending aortic banding the hypertrophic phenotype is asso ciated with a selective reinduction of the fetal gene program, which p ersists even after the development of left ventricular failure. Furthe rmore, the hypertrophic gene program that accompanies hypertrophy and failure is dissociated from changes in Ca2+-ATPase expression. The dec rease in Ca2+-ATPase mRNA levels may be a marker of the transition fro m compensatory hypertrophy to failure in these animals.