Oxidative Stress-Dependent Coronary Endothelial Dysfunction in Obese Mice

Area of Science:

• Cardiovascular Science
• Endocrinology
• Physiology

Background:

• Obesity is a significant risk factor for cardiovascular diseases, including coronary artery disease.
• Endothelial function, regulated by vasodilators and vasoconstrictors, is crucial for maintaining vascular tone.
• Diet-induced obesity models are vital for studying the mechanisms of cardiovascular complications.

Purpose of the Study:

• To investigate the impact of diet-induced obesity on coronary vascular response in mice.
• To assess the role of oxidative stress and vasoactive substances in obesity-related endothelial dysfunction.
• To evaluate the therapeutic potential of NADPH oxidase inhibition in reversing these effects.

Main Methods:

• Utilized an 8-week diet-induced obesity model in C57BL/6 mice.
• Measured coronary perfusion pressure responses to acetylcholine in isolated hearts.
• Assessed vascular nitric oxide, prostacyclin, tetrahydrobiopterin, and oxidative stress markers (superoxide, peroxynitrite).
• Evaluated endothelial nitric oxide synthase (eNOS) dimer/monomer ratio and thromboxane A2 synthesis.
• Administered apocynin, a NADPH oxidase inhibitor, to obese mice.

Main Results:

• Obese mice exhibited increased coronary vasoconstriction and reduced vasodilation compared to controls.
• Diminished nitric oxide bioavailability and reduced prostacyclin release were observed in obese mice.
• Increased oxidative stress markers (superoxide, peroxynitrite) and thromboxane A2 synthesis were noted.
• Apocynin treatment successfully reversed obesity-induced endothelial dysfunction and normalized all measured parameters.

Conclusions:

• Eight weeks of high-fat diet-induced obesity leads to endothelial dysfunction in coronary arteries.
• Increased oxidative stress plays a critical role in the imbalance of vasoactive substances.
• Inhibition of NADPH oxidase with apocynin effectively ameliorates obesity-related endothelial dysfunction.