Mito-targeted antioxidant prevents cardiovascular remodelling in spontaneously hypertensive rat by modulation of energy metabolism [Mass Spectrometry - Proteomics Facility]

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TitleMito-targeted antioxidant prevents cardiovascular remodelling in spontaneously hypertensive rat by modulation of energy metabolism [Mass Spectrometry - Proteomics Facility]
Publication TypeJournal Article
Year of Publication2021
AuthorsPotnuri AGodwin, Purushothaman S, Saheera S, Nair RR
JournalClinical and Experimental Pharmacology and Physiology
Date Published08/2021
Type of ArticleJournal Article
Keywordscardiac hypertrophy, cardiac metabolism, LC-MS, mitochondria targeted antioxidant, proteomic analysis, spontaneously hypertensive rat
Abstract

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.

URLhttps://onlinelibrary.wiley.com/doi/10.1111/1440-1681.13585
DOI10.1111/1440-1681.13585
PubMed ID34459495