[Cellular mechanisms of human atherosclerosis]

Area of Science:

• Vascular Biology
• Cellular Ultrastructure
• Lipid Metabolism

Context:

• Scanning electron microscopy reveals unique endothelial cell structures in human arteries, differing from animal models.
• Lipid streaks and atherosclerotic plaques exhibit polymorphous endothelium, with multinucleated endotheliocytes covering over 50% of the surface.
• These pathological areas demonstrate increased absorption of native low-density lipoproteins (LDL) via non-specific binding.

Purpose:

• To investigate the structural and functional characteristics of the human arterial endothelium in relation to lipoprotein uptake.
• To compare LDL absorption mechanisms in normal versus atherosclerotic human aortic endothelial cells.
• To explore the potential of cellular cultures for identifying novel pharmacological agents targeting lipoprotein metabolism.

Summary:

• Human arterial endothelium displays unique features, particularly in atherosclerotic regions, characterized by multinucleated cells and enhanced non-specific binding of native LDL.
• Modified LDL are primarily absorbed through scavenger receptors in both normal and atherosclerotic intima.
• Human hepatocytes exhibit high-affinity uptake of modified LDL, and enterocytes possess numerous high-density lipoprotein binding sites, indicating complex lipoprotein handling.
• Cultured human cells offer a platform for discovering drugs to correct lipoprotein and cholesterol metabolism disorders.

Impact:

• Provides novel insights into the ultrastructural basis of lipoprotein accumulation in atherosclerosis.
• Highlights differences in LDL receptor-mediated and non-specific uptake pathways in human arteries.
• Establishes the utility of primary human cell cultures (hepatocytes, enterocytes, endothelial cells) for studying lipoprotein metabolism and drug discovery.
• Suggests potential therapeutic strategies targeting specific lipoprotein interactions with endothelial cells, hepatocytes, and enterocytes.