Hyaluronan-CD44-ERK1/2 regulate human aortic smooth muscle cell motility during aging

Area of Science:

• Vascular Biology
• Aging Research
• Biochemistry

Background:

• Hyaluronan (HA) is a glycosaminoglycan involved in vascular pathologies like atherosclerosis.
• Aging is a key risk factor for vascular diseases, with smooth muscle cells (SMCs) playing a crucial role in neointima formation.
• SMC migration and proliferation are central to neointima development.

Purpose of the Study:

• To investigate the role of hyaluronan (HA) in aging-related vascular smooth muscle cell (SMC) behavior.
• To elucidate the mechanisms by which aging affects HA synthesis and signaling in human aortic smooth muscle cells (AoSMCs).

Main Methods:

• Established an in vitro aging model using sequential passages of human aortic smooth muscle cells (AoSMCs).
• Quantified HA synthesis, expression of HA synthetic enzymes (HAS2, HAS3), UDP-glucose dehydrogenase, and HA receptor CD44 in young versus aged AoSMCs.
• Assessed CD44 signaling, including ERK1/2 phosphorylation, and measured AoSMC migration rates.
• Investigated the effects of HA oligosaccharides and anti-CD44 antibody on cell migration and signaling.

Main Results:

• Aging significantly increased HA synthesis, HAS2, HAS3, UDP-glucose dehydrogenase, and CD44 expression in AoSMCs.
• Aged AoSMCs exhibited elevated CD44 signaling, evidenced by increased phosphorylated ERK1/2 (p-ERK1/2).
• Aged AoSMCs showed enhanced migration, which was modulated by HA and involved CD44-mediated ERK1/2 phosphorylation.
• HA oligosaccharides and anti-CD44 antibody inhibited p-ERK1/2 and reduced AoSMC migration.

Conclusions:

• In vitro aging of AoSMCs leads to increased HA production and enhanced migratory capacity.
• HA modulates SMC migration via CD44-mediated signaling, specifically involving the ERK1/2 pathway.
• Age-related accumulation of HA may promote SMC migration and intima thickening in vascular diseases.