In vivo collagen turnover during development of thyroxine-induced left ventricular hypertrophy.
Cardiac fibroblasts synthesize large amounts of procollagens, yet only a small fraction of mature collagens accumulate in the extracellular matrix. To determine the roles of intracellular degradation of newly synthesized procollagens and extracellular degradation of mature collagens during normal growth and during thyroxine-induced left ventricular hypertrophy, in vivo left ventricular procollagen synthetic rates were assessed in control rats and rats treated with L-thyroxine for 1, 2, 4, and 8 wk (1 mg.kg-1.day-1). A modification of the flooding infusion method was developed using measurements of cardiac prolyl-tRNA, and tissue-free and protein-bound hydroxyproline specific radioactivities 60 min after intravenous administration of a massive dose of [3H]proline. Degradative rates of newly synthesized procollagens and mature collagens were then derived as the difference between rates of procollagen synthesis and collagen accumulation. Left ventricular procollagen synthetic rates were markedly increased after 1 wk of hormone administration (256 +/- 16 and 166 +/- 13 micrograms/day per left ventricle for thyroxine-treated and control animals, respectively; P less than 0.01). An even greater increase in procollagen synthetic rates was observed after 8 wk (438 +/- 46 and 202 +/- 18 micrograms/day for thyroxine-treated and control animals, respectively; P less than 0.01). Despite increased procollagen synthesis, disproportionate accumulation of fibrillar collagens (assessed as the relative concentration of protein-bound hydroxyproline in left ventricular tissue) did not occur. Derived left ventricular degradative rates for newly synthesized procollagens as well as for mature collagens were increased in thyroxine-treated animals. Increased procollagen synthesis, enhanced flux of newly synthesized procollagens through intracellular degradative pathways, and extensive extracellular matrix remodeling without disproportionate collagen accumulation are characteristics of this form of "physiological" left ventricular hypertrophy.
Karim
M A
MA
Department of Medicine, Loyola University Stritch School of Medicine, Maywood, Illinois 60153.
Ferguson
A G
AG
Wakim
B T
BT
Samarel
A M
AM
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism*; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011392:Proline / Q000097:blood / Q000378:metabolism; D012361:RNA, Transfer, Pro / Q000378:metabolism; D011865:Radioisotope Dilution Technique; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013974:Thyroxine / Q000494:pharmacology*; D014316:Tritium
D012361:RNA, Transfer, Pro; D014316:Tritium; D003094:Collagen; D011392:Proline; D013974:Thyroxine