Abstract
Background: The endogenous opioid system plays a pivotal role in numerous physiological processes and is implicated in a range of diseases, including atherosclerosis, a condition contributing to nearly 50% of deaths in Western societies. Objectives: This study investigates the effects of opioid receptor blockade, using naloxone, on the plasma lipid profile and atherosclerosis progression. Methods: ApoE(-/-) mice with advanced atherosclerosis were treated with naloxone for seven days, and the effects on atherosclerotic plaque development and liver steatosis were evaluated. Results: A proteomic analysis of liver samples post-treatment identified 38 proteins with altered abundance. The results revealed that naloxone treatment led to an increase in HDL cholesterol, a lipid fraction associated with protective cardiovascular effects. Furthermore, naloxone did not influence the progression of atherosclerotic plaques or the development of liver steatosis. Conclusions: In conclusion, while short-term naloxone treatment in mice with advanced atherosclerosis does not alter overall atherosclerotic plaque progression or liver steatosis, the observed elevation in HDL cholesterol and the extensive changes in liver protein abundance underscore the complex and multifaceted role of the opioid system in lipid metabolism and cardiovascular health. These findings provide a foundation for further exploration of opioid receptor antagonists as modulators of lipid profiles and potential contributors to cardiovascular therapy.