REGULATION VON PROTEINBIOSYNTHESE UND C-MYC-EXPRESSION BEI LINKSVENTRIKULARER HYPERTROPHIE

The effects of growth promoting stimuli on cardiac protein synthesis and c-myc mRNA expression were studied in isolated perfused rat hearts with chronic left ventricular pressure overload (8 weeks banding of the ascending aorta, LVH) and sham operated controls. New protein synthesis (incorporation of ³H-phenylalanine [Phe]) and c-myc mRNA levels (Northern blot) were analysed after a 3-hour perfusion protocol. Under baseline conditions, Phe-incorporation (250 nmoles/gram protein/h) and c-myc mRNA levels were similar in control (n = 6) and LVH hearts (n = 5). In control hearts, infusion of angiotensin II (AII; 10^-8 M plus prazosin 10^-7 M; n = 6) or norepinephrine (Nor, 10^-6M, n = 5) were related to a 4-fold (AII, p < 0.001) and 2-fold (Nor, p < 0.05) induction of Phe-incorporation in both left and right ventricles. In contrast, perfusion of LVH-hearts resulted in small (AII: 1.5-fold; n = 6; p = NS) or no (Nor; n = 5) induction of cardiac protein synthesis that was significantly lower than in respective control groups (p < 0.005 and p < 0.05). Imposition of cardiac load (100 mmHg/g LV, n = 5) increased Phe-incorporation 1.7-fold (p < 0.05) and c-myc mRNA levels 3-fold (p < 0.05) in the stressed left ventricles of control hearts. Stimulation of LVH-hearts with identical wall stress resulted in a blunted induction of both Phe-incorporation and c-myc mRNA. In summary, the data suggest that in contrast to baseline metabolism acute induction of protein synthesis by neurohumoral or mechanical stimulation may be altered in hearts with established LVH.