Y. Nagatomo et al., Translational mechanisms accelerate the rate of protein synthesis during canine pressure-overload hypertrophy, AM J P-HEAR, 277(6), 1999, pp. H2176-H2184
Citations number
41
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
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.