Hyperlipidemia and endothelial dysfunction: effects of eNOS phosphorylation and vascular ultrastructure in normoglycemic <i>Psammomys obesus</i>

Atherosclerosis represents the most prevalent form of cardiovascular disease, with the potential to ultimately result in clinically significant complications such as myocardial infarction and stroke. The objective of our study was to gain a deeper understanding of the independent role of hyperlipidemia in the development of endothelial dysfunction and ultrastructural damage to the arteries, which is a key factor in the pathogenesis of atherosclerosis. Following a 12-week dietary intervention comprising either a high-energy diet (HED) or a normal diet (ND), fasting plasma glucose and lipid parameters were assessed. The aortas were subjected to histological analysis and Western blotting, while the carotid arteries underwent ultrastructural analysis using transmission electron microscopy. HED resulted in a statistically significant elevation in lipid parameters, even in normoglycemic <i>P. obesus</i>. eNOS, phospho-eNOS (Thr 495), and NF-κB p65 protein expression were increased in the aorta of HED-fed <i>P. obesus</i>. Histological examination and ultrastructural analysis of HED-fed <i>P. obesus</i> demonstrated notable vascular remodeling, manifested by segmental arterial wall thickening and the presence of large vacuoles and lipid droplets in endothelial cells. This study provides evidence that hyperlipidemia is a significant contributing factor to endothelial dysfunction and ultrastructural alterations in blood vessels, even in the absence of severe hyperglycemia.