Mitochondrial tRNA mutation with high-salt stimulation on cardiac damage: underlying mechanism associated with change of Bax and VDAC.

Mitochondrial transfer RNA (tRNA) mutation with high-salt stimulation can cause high blood pressure. However, the underlying mechanisms remain unclear. In the present study, we examined the potential molecular mechanisms of cardiac damage caused by mitochondrial tRNA mutation with high-salt stimulation in spontaneously hypertensive rats (SHR). Unanesthetized, 44-wk-old, male, SHR were divided into four groups: SHR, SHR with high-salt stimulation for 8 wk (SHR + NaCl), SHR carrying tRNA mutations (SHR + M), and SHR + M with high-salt stimulation for 8 wk (SHR + M + NaCl). Healthy Wistar-Kyoto (WKY) rats were used as controls. Left ventricular mass and interventricular septum were highest in the SHR + M + NaCl group (P < 0.05), while ejection fraction was lowest in the SHR + M + NaCl group (P < 0.05). Hematoxylin and eosin staining showed myocardial cell hypertrophy with interstitial fibrosis and localized inflammatory cell infiltration, in the hypertensive groups, particularly in the SHR + M + NaCl group. Electron microscopy showed different degrees of mitochondrial cavitation in heart tissue of the hypertensive groups, which was highest in the SHR + M + NaCl group. In hypertensive animals, levels of reactive oxygen species were highest in the SHR + M + NaCl group (P < 0.05). Expression of the voltage-dependent anion channel (VDAC) and the apoptosis regulator Bax were highest in the SHR + M + NaCl group (P < 0.05), which also showed evidence of VDAC and Bax colocalization (P < 0.05). Overall, these data suggest that mitochondrial tRNA mutation with high-salt stimulation can aggravate cardiac damage, potentially because of increased expression and interaction between Bax and VDAC and increased reactive oxygen species formation and initiation of apoptosis.