Proatherogenic stimuli induce HuR in atherosclerosis through MAPK/ErK pathway

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Endothelial Cell Biology

Background:

• Atherosclerosis is a chronic inflammatory arterial disease.
• Endothelial activation and dysfunction are key to its pathogenesis.
• The role of RNA-binding protein HuR in atherosclerosis is not well understood.

Purpose of the Study:

• To investigate the role and regulation of HuR in atherosclerosis.
• To determine the impact of proatherogenic stimuli on HuR expression.
• To elucidate the signaling pathways involved in HuR induction.

Main Methods:

• Examined HuR expression and activity in human and mouse atherosclerotic lesions.
• Utilized human aortic endothelial cells (HAECs) and mouse aorta endothelial cells (ECs) in vitro and in vivo.
• Applied proatherogenic stimuli like Ox-PAPC, TNF-α, IL-1β, and high-fat diet.
• Investigated the involvement of the MAPK/ErK signaling pathway.

Main Results:

• HuR expression and RNA-binding activity are increased in atherosclerotic lesions.
• Proatherogenic stimuli (lipids, cytokines) and high-fat diet induce HuR in endothelial cells.
• HuR induction correlates with hyperlipidemia in mice on a high-fat diet.
• The MAPK/ErK pathway is activated by proatherogenic stimuli and is essential for HuR induction.

Conclusions:

• Proatherogenic stimuli induce HuR in endothelial cells.
• The MAPK/ErK pathway mediates HuR induction in response to these stimuli.
• This study links HuR regulation to key pathways in atherosclerosis pathogenesis.