MITOCHONDRIAL BIOGENESIS DURING PRESSURE-OVERLOAD INDUCED CARDIAC-HYPERTROPHY IN ADULT-RATS

Existing literature provides an equivocal picture of the behavior of m itochondrial synthesis during the time course of cardiac hypertrophy. Therefore, we examined the effect of cardiac hypertrophy on mitochondr ial cytochrome c oxidase (CYTOX) activity, the content of CYTOX subuni t VIc mRNA, and the expression of molecular chaperones. Adult male Spr ague-Dawley rats were subjected to either abdominal aortic constrictio n to induce pressure overload (PO) or a sham operation (SH). Animals w ere studied 2, 4, 7, 14, 21, or 28 days after surgery. Aortic constric tion resulted in a significant elevation in arterial pressure by 4 day s after surgery. Significant (p < 0.05) hypertrophy was attained by 4 days and was stabilized at 37% between 7 and 28 days. CYTOX activity ( U/g) did not differ significantly between PO and SH animals at either early (<7 days) or later time points, indicating that mitochondrial co ntent increased in proportion to adaptive cellular hypertrophic growth . The concentration of the molecular chaperones HSP60 and GRP75 involv ed in mitochondrial protein import did not change with PO treatment. T he levels of mRNAs encoding both CYTOX subunit VIc and HSP60 remained constant, in proportion to cardiac growth. This suggests that the acce lerated synthesis of CYTOX and HSP60 during cardiac hypertrophy is reg ulated transcriptionally. The data help to resolve the controversy in the literature regarding mitochondrial biogenesis during moderate, sta ble cardiac hypertrophy, and they indirectly indicate that proportiona l mitochondrial synthesis relative to cellular hypertrophy is regulate d at the transcriptional level.