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A Model of Cardiac Remodeling Through Constriction of the Abdominal Aorta in Rats
Published on: December 2, 2016
Cardamonin Alleviates Pressure Overload-induced Cardiac Remodeling and Dysfunction Through Inhibition of Oxidative
Wei Li1, Xiangqi Wu, Minghui Li
1Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Insights
Cardamonin, a chalcone, protects against heart failure by reducing oxidative stress and apoptosis. This study shows cardamonin can attenuate cardiac remodeling and dysfunction caused by pressure overload.
Area of Science:
- Cardiovascular Research
- Oxidative Stress Biology
- Pharmacology
Background:
- Pressure overload leads to cardiac remodeling and heart failure, primarily driven by oxidative stress.
- Chalcones, like cardamonin, are being investigated for potential therapeutic benefits in cardiovascular diseases.
Purpose of the Study:
- To investigate if cardamonin can mitigate maladaptive cardiac changes and dysfunction induced by pressure overload.
- To elucidate the antioxidant mechanisms underlying cardamonin's protective effects on the heart.
Main Methods:
- In vivo studies using transverse aortic constriction to induce cardiac remodeling in animal models.
- In vitro experiments utilizing H9C2 cells treated with angiotensin II, hydrogen peroxide, or Nox4 overexpression.
- Assessment of oxidative stress markers (superoxide dismutase, L-glutathione, malonaldehyde) and apoptosis-related proteins (Bax, Bcl-2, caspase-3, etc.).
Main Results:
- Cardamonin treatment attenuated cardiac remodeling and dysfunction in vivo.
- Cardamonin significantly reduced oxidative stress and apoptosis in H9C2 cells exposed to various stressors.
- Cardamonin modulated the expression of key apoptosis-related proteins, decreasing pro-apoptotic factors and increasing anti-apoptotic factors.
Conclusions:
- Cardamonin exhibits significant cardioprotective effects against pressure overload-induced heart failure.
- The antioxidant and anti-apoptotic properties of cardamonin are key mechanisms for its therapeutic potential.
- Cardamonin presents a promising therapeutic candidate for managing heart failure associated with oxidative stress.
Abstract:
Pressure overload-induced cardiac remodeling and dysfunction progress to heart failure, which is mainly due to excessive oxidative stress. Hence, our study aimed to illustrate whether cardamonin, a kind of chalcone, could attenuate maladaptive cardiac changes and ameliorate cardiac insufficiency through its antioxidant mechanism. In vivo, our study revealed that cardamonin treatment could attenuate transverse aortic contraction-induced cardiac remodeling and dysfunction. Histological observations have suggested that cardamonin inhibited the occurrence of excessive cardiac oxidative stress and apoptosis. In vitro, we found that 3 treatments with angiotensin II (Ang II), hydrogen peroxide, and Nox4 overexpression in H9C2 cells markedly augmented intracellular oxidative stress as measured by superoxide dismutase, L-glutathione, and malonaldehyde. Conversely, cardamonin treatment notably alleviated oxidative stress induced by the 3 above-mentioned treatments. Furthermore, all 3 treatments resulted in increased apoptotic cell death, whereas cardamonin treatment reduced apoptosis in H9C2 cells. Moreover, cardamonin significantly abrogated the expression of Bax, apoptosis inducing factor, cytochrome c, and caspase-3 and caspase-9 and enhanced the expression of Bcl-2 and Bcl-xl. In conclusion, these findings provide a new possibility for cardamonin to alleviate pressure overload-induced heart failure.
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