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Published on: September 25, 2017
STVNa Attenuates Isoproterenol-Induced Cardiac Hypertrophy Response through the HDAC4 and Prdx2/ROS/Trx1 Pathways
1Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China.
Insights
Isosteviol sodium (STVNa) protects against cardiac hypertrophy by restoring mitochondrial function and reducing oxidative stress. This compound shows potential for treating heart conditions like cardiac hypertrophy.
Area of Science:
- Cardiology
- Mitochondrial Biology
- Pharmacology
Background:
- Cardiac hypertrophy is a significant contributor to heart failure.
- Mitochondrial dysfunction is a hallmark of cardiac hypertrophy.
- Isosteviol has demonstrated protective effects against myocardial ischemia-reperfusion injury.
Purpose of the Study:
- To investigate the protective mechanisms of isosteviol sodium (STVNa) against isoproterenol (Iso)-induced cardiac hypertrophy.
- To elucidate the role of STVNa in mitochondrial function and oxidative stress in cardiac hypertrophy.
Main Methods:
- Utilized H9c2 cells and rat primary cardiomyocytes.
- Induced cardiac hypertrophy using isoproterenol (Iso).
- Assessed cell surface area, mitochondrial membrane potential (MMP), mitochondrial morphology, protein expression (Fis1, Drp1, Trx1, Prdx2), reactive oxygen species (ROS) levels, and histone deacetylase 4 (HDAC4) activity.
Main Results:
- STVNa significantly inhibited cardiomyocyte hypertrophy.
- STVNa restored MMP and mitochondrial integrity.
- STVNa decreased Fis1 and Drp1 expression, reduced ROS levels, and upregulated Trx1 and Prdx2 expression.
- STVNa restored nuclear HDAC4 activity.
Conclusions:
- STVNa confers protection against isoproterenol-induced cardiac hypertrophy.
- The protective effects are mediated through the Prdx2/ROS/Trx1 signaling pathway.
- STVNa is a potential therapeutic agent for human cardiac hypertrophy.
Abstract:
Recent data show that cardiac hypertrophy contributes substantially to the overall heart failure burden. Mitochondrial dysfunction is a common feature of cardiac hypertrophy. Recent studies have reported that isosteviol inhibits myocardial ischemia-reperfusion injury in guinea pigs and H9c2 cells. This work investigated the protective mechanisms of isosteviol sodium (STVNa) against isoproterenol (Iso)-induced cardiac hypertrophy. We found that STVNa significantly inhibited H9c2 cell and rat primary cardiomyocyte cell surface, restored mitochondrial membrane potential (MMP) and morphological integrity, and decreased the expression of mitochondrial function-related proteins Fis1 and Drp1. Furthermore, STVNa decreased reactive oxygen species (ROS) levels and upregulated the expression of antioxidant factors, Thioredoxin 1 (Trx1) and Peroxiredoxin 2 (Prdx2). Moreover, STVNa restored the activity of histone deacetylase 4 (HDAC4) in the nucleus. Together, our data show that STVNa confers protection against Iso-induced myocardial hypertrophy primarily through the Prdx2/ROS/Trx1 signaling pathway. Thus, STVNA is a potentially effective treatment for cardiac hypertrophy in humans.
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