Effects of hypothyroidism and aortic construction on mitochondria during cardiac hypertrophy.
We evaluated mitochondrial adaptations in the hearts of euthyroid and hypothyroid rats subject to aortic constriction for 2, 4, 7, 14, 21, and 28 d to induce a pressure-overload (PO), compared to sham-operated (SH) controls. PO animals attained higher arterial pressures than SH animals, by 55% in the euthyroid group, but only 14% in hypothyroid rats after 28 d. The left ventricle/body weight ratio was increased 44% by PO in the euthyroid group, and 26% in the hypothyroid group. PO attenuated the decline in cardiac growth in the hypothyroid group. Thus, hypothyroidism reduces the magnitude of the PO, but not the potential for hypertrophy in response to PO. Cytochrome c oxidase activity (CYTOX) was unchanged by PO in the euthyroid animals, indicating that the synthesis of mitochondria paralleled adaptive growth. However, CYTOX activity decreased up to 20% in the hypothyroid groups (P < 0.05) and was unaltered by PO. Thus, PO prevented the decline in growth, but not the decline in mitochondrial enzymes due to hypothyroidism. The lack of effect of PO on mitochondria was partly due to pretranslational changes since CYTOX subunit VIc mRNA was reduced by PO in the hypothyroid animals, but not in the euthyroid group. Levels of the chaperones HSP60 and GRP75, as well as HSP60 mRNA were unaffected by hypothyroidism, but paralleled adaptive growth induced by PO. Hypothyroidism changes the pattern of gene expression within the heart leading to altered mitochondrial composition. This cannot be compensated for by conditions of increased physiological demand.
Nishio
M L
ML
School of Physical Education, York University, Canada.
Ornatsky
O I
OI
Hood
D A
DA
D000818:Animals; D000831:Animals, Newborn; D001012:Aorta, Abdominal / Q000503:physiopathology*; D018834:Chaperonin 60; D003251:Constriction, Pathologic; D003576:Electron Transport Complex IV / Q000378:metabolism*; D007037:Hypothyroidism / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism*; D011312:Pressure; D012333:RNA, Messenger; D051381:Rats
D018834:Chaperonin 60; D012333:RNA, Messenger; D003576:Electron Transport Complex IV