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NADPH oxidase 4 contributes to oxidative stress in a mouse model of myocardial infarction
1Department of Geratology, Jiangnan University Medical Center, JUMC, Wuxi, Jiangsu Province, China. yanping03060130@sina.com.
Abstract:
Oxidative stress closely related to the progression and severity of myocardial infarction (MI). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) is one of the major enzymes that generate reactive oxygen species (ROS) in cardiovascular system. Here, we aim to elucidate the pathological role of NOX4 in MI. MI mouse model was created by the coronary artery ligation. NOX4 was specifically knocked down in heart through intramyocardial injection of siRNA. NOX4 expression and oxidative stress indicators were determined at different time points using qRT-PCR, Western blot, and ELISA, and then analyzed by Pearson's correlation. Cardiac function was evaluated by using echocardiographic technique. NOX4 was upregulated in myocardial tissues of MI mice, which positively correlated with the elevation of oxidative stress indicators. Knockdown of NOX4 in heart significantly reduced the production of ROS and the level of oxidative stress in left ventricle tissues, which was accompanied by significant improvement of cardiac function in MI mice. Selective knockdown of NOX4 in heart attenuates MI-induced oxidative stress and improves cardiac function, suggesting inhibition of NOX4/ROS axis in heart using siRNA is a potential therapeutic treatment for MI-induced cardiac dysfunction.
Insights
Targeting Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) with siRNA in the heart reduces oxidative stress and improves cardiac function following myocardial infarction (MI). This suggests NOX4 inhibition as a potential therapy for heart dysfunction.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Oxidative Stress Research
Background:
- Oxidative stress is a key factor in myocardial infarction (MI) progression and severity.
- Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) is a primary source of reactive oxygen species (ROS) in the cardiovascular system.
Purpose of the Study:
- To investigate the pathological role of NOX4 in myocardial infarction (MI).
- To evaluate the therapeutic potential of inhibiting NOX4 in MI-induced cardiac dysfunction.
Main Methods:
- Established a myocardial infarction (MI) mouse model using coronary artery ligation.
- Utilized intramyocardial injection of small interfering RNA (siRNA) for specific cardiac NOX4 knockdown.
- Quantified NOX4 expression, ROS production, and oxidative stress markers via qRT-PCR, Western blot, and ELISA.
- Assessed cardiac function using echocardiography.
Main Results:
- NOX4 expression was upregulated in MI mouse hearts and correlated positively with oxidative stress indicators.
- Cardiac NOX4 knockdown significantly reduced ROS production and oxidative stress in the left ventricle.
- NOX4 inhibition led to a significant improvement in cardiac function in MI mice.
Conclusions:
- Selective NOX4 knockdown in the heart attenuates MI-induced oxidative stress and improves cardiac function.
- The NOX4/ROS axis in the heart represents a promising therapeutic target for MI-induced cardiac dysfunction.
- siRNA-mediated inhibition of NOX4 offers a potential treatment strategy for myocardial infarction.
