Endothelial cell injury in early mild hypercholesterolemia

Area of Science:

• Cardiovascular Biology
• Atherosclerosis Research
• Endothelial Cell Biology

Background:

• Hypercholesterolemia is a major risk factor for atherosclerosis.
• Early endothelial dysfunction is critical in atherogenesis.
• Understanding leukocyte-endothelial interactions is key to preventing cardiovascular disease.

Purpose of the Study:

• To investigate early changes in aortic endothelium during diet-induced hypercholesterolemia in swine.
• To examine leukocyte adhesion and endothelial cell morphology in relation to vascular permeability.

Main Methods:

• Male swine were fed a cholesterol and lard-supplemented diet to induce hypercholesterolemia.
• Aortic samples were analyzed using light and electron microscopy at 2, 4, and 6 weeks.
• Evans blue dye was used to demarcate areas of differing protein permeability.

Main Results:

• Cholesterol/lard-fed swine showed increased leukocyte adhesion to the aortic endothelium, especially in high-permeability areas.
• Endothelial cells exhibited increased lysosomes and cytoplasmic filaments, with ruthenium red uptake beneath adhered leukocytes.
• Blood-derived cells were frequently observed in the intima, associated with endothelial intercellular junctions.

Conclusions:

• Diet-induced hypercholesterolemia promotes leukocyte adhesion to the swine aortic endothelium.
• Early endothelial cell alterations, including increased lysosomes and filaments, occur in response to hyperlipidemia.
• Leukocyte and blood-derived cell infiltration into the intima suggests early atherogenic processes are initiated.