Hyaluronan forms complexes with low density lipoprotein while also inducing foam cell infiltration in the dermis

Area of Science:

• Biochemistry
• Dermatology
• Cell Biology

Background:

• Xanthoma, a lesion characterized by foam cell infiltration, shares similarities with atherosclerosis.
• Glycosaminoglycans and proteoglycans are implicated in the pathogenesis of atherosclerosis.

Purpose of the Study:

• To investigate the role of hyaluronan, the primary glycosaminoglycan in the dermis, in the formation of xanthoma.
• To understand the interaction between hyaluronan and low-density lipoprotein (LDL) in the context of xanthoma development.

Main Methods:

• Assayed cholesterol levels in precipitates formed by incubating LDL, hyaluronan, and cetylpyridinium chloride with Ca2+ to study complex formation.
• Investigated LDL uptake by mouse peritoneal macrophages by measuring cellular cholesterol esterification.
• Examined LDL internalization receptors by saturating hyaluronan receptors and blocking class A macrophage scavenger receptor (CD204).
• Injected hyaluronan into hypercholesterolemic rabbits to assess its xanthoma-inducing activity.

Main Results:

• Hyaluronan formed complexes with LDL, precipitated by cetylpyridinium chloride.
• Macrophages incorporated hyaluronan-LDL complexes and oxidized LDL through the CD204 receptor.
• Intradermal hyaluronan injections in hypercholesterolemic rabbits induced foam cell infiltration and cholesterol accumulation, characteristic of xanthoma.

Conclusions:

• Hyaluronan, similar to sulfated glycosaminoglycans, retains LDL by forming complexes.
• Macrophages internalize LDL-hyaluronan complexes and oxidized LDL via macrophage scavenger receptors (CD204).
• This mechanism highlights hyaluronan's role in promoting xanthoma formation through LDL retention and macrophage uptake.