Translational mechanisms accelerate the rate of protein synthesis during canine pressure-overload hypertrophy

This study examined how translational mechanisms regulate the rate of cardi ac protein synthesis during canine pressure overload in vivo. Acute aortic stenosis (AS) was produced by inflating a balloon catheter in the ascending aorta for 6 h; sustained AS was created by controlled banding of the ascen ding aorta. AS caused significant hypertrophy as reflected by increased lef t ventricular (LV) mass after 5 and 10 days. To monitor LV protein synthesi s in vivo, myosin heavy chain (MHC) synthesis was measured by continuous in fusion of radiolabeled leucine. Acute AS accelerated the rate of myosin syn thesis without a corresponding increase in ribosomal RNA, indicating an inc rease in translational efficiency. Total MHC synthesis (mg MHC/LV per day) was significantly increased at 5 and 10 days of sustained AS. Total MHC deg radation was not significantly altered at 5 days of AS but increased at 10 days of AS in concordance with a new steady state with respect to growth. T ranslational capacity (mg total RNA/LV) was significantly increased after 5 and 10 days of AS and was preceded by an increase in the rate of ribosome formation. MHC mRNA levels remained unchanged during AS. These findings dem onstrate that cardiac protein synthesis is accelerated in response to press ure overload by an initial increase in translational efficiency, followed b y an adaptive increase in translational capacity during sustained hypertrop hic growth.