Key result
Mito-TEMP (2 mg/kg/day) was superior to the non-targeted isoform TEMP (20 mg/kg/day) in preventing hypertension-induced left ventricular hypertrophy and reversing metabolic remodeling in rats.
Why the study?
To assess whether the mito-targeted antioxidant Mito-Tempol is more effective than the general antioxidant Tempol in reducing hypertension and hypertrophy and preventing shifts in cardiac energy metabolism.
Does Mito-Tempol prevent cardiovascular remodeling and shift in cardiac energy metabolism better than Tempol in spontaneously hypertensive rats?
Does Mito-Tempol prevent cardiovascular remodeling and shift in cardiac energy metabolism better than Tempol in spontaneously hypertensive rats?
Mito-targeted antioxidants may be superior to general antioxidants in preventing hypertension-induced left ventricular hypertrophy and metabolic remodeling.
Mito-Tempol may attenuate hypertensive LVH in rodents; leaves open human translation and clinical trials.
Hypertension induced left ventricular hypertrophy (LVH) augments the risk of cardiovascular anomalies. Mitochondrial alterations result in oxidative stress, accompanied by decrease in fatty acid oxidation, leading to the activation of the hypertrophic program. Targeted antioxidants are expected to reduce mitochondrial reactive oxygen species more effectively than general antioxidants. This study was designed to assess whether the mito-targeted antioxidant, Mito-Tempol (Mito-TEMP) is more effective than the general oxidant, Tempol (TEMP) in reduction of hypertension and hypertrophy and prevention of shift in cardiac energy metabolism. Spontaneously hypertensive rats were administered either TEMP (20 mg/kg/day) or Mito-TEMP (2 mg/kg/day) intraperitoneally for 30 days. Post treatment, animals were subjected to 2D-echocardiography. Myocardial lysates were subjected to RPLC - LTQ-Orbitrap-MS analysis. Mid-ventricular sections were probed for markers of energy metabolism and fibrosis. The beneficial effect on cardiovascular structure and function was significantly higher for Mito-TEMP. Increase in mitochondrial antioxidants and stimulation of fatty acid metabolism; with significant improvement in cardiovascular function was apparent in spontaneously hypertensive rats (SHR) treated with Mito-TEMP. The study indicates that Mito-TEMP is superior to its non- targeted isoform in preventing hypertension induced LVH, and the beneficial effects on heart are possibly mediated by reversal of metabolic remodelling.
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Potnuri et al. (2021) studied Hypertension induced left ventricular hypertrophy. Mito-Tempol (Mito-TEMP) vs. Tempol (TEMP) 20 mg/kg/day was evaluated on Reduction of hypertension and hypertrophy and prevention of shift in cardiac energy metabolism. Mito-TEMP (2 mg/kg/day) was superior to the non-targeted isoform TEMP (20 mg/kg/day) in preventing hypertension-induced left ventricular hypertrophy and reversing metabolic remodeling in rats.
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