Ghrelin suppresses inflammation in HUVECs by inhibiting ubiquitin-mediated uncoupling protein 2 degradation

Area of Science:

• Cardiovascular Biology
• Cellular Inflammation
• Endothelial Cell Function

Background:

• Atherosclerosis is a leading cause of mortality, driven by inflammation, but its pathogenesis remains unclear.
• Oxidized low-density lipoprotein (oxLDL) is implicated in atherosclerosis development.
• Inflammation is recognized as a critical factor throughout all stages of atherosclerosis.

Purpose of the Study:

• To investigate the effect of ghrelin on oxidized low-density lipoprotein (oxLDL)-induced inflammation in human umbilical vein endothelial cells (HUVECs).
• To explore the role of uncoupling protein 2 (UCP2) in ghrelin's anti-inflammatory actions.
• To elucidate the mechanism by which ghrelin influences UCP2 levels.

Main Methods:

• Treatment of HUVECs with ghrelin and oxLDL.
• Measurement of inflammatory responses and reactive oxygen species (ROS) generation.
• siRNA-mediated knockdown of UCP2 expression.
• Analysis of UCP2 ubiquitination and degradation pathways.

Main Results:

• Ghrelin significantly inhibited the oxLDL-induced inflammatory response in HUVECs.
• Ghrelin treatment increased cellular uncoupling protein 2 (UCP2) levels, reducing reactive oxygen species (ROS) generation.
• UCP2 accumulation, mediated by ghrelin's inhibition of UCP2 ubiquitination and degradation, was essential for the anti-inflammatory effect.

Conclusions:

• Ghrelin demonstrates potential as an anti-atherosclerotic agent by inhibiting oxLDL-induced inflammation in endothelial cells.
• The anti-inflammatory effects of ghrelin are dependent on the accumulation of UCP2.
• This study provides novel insights into atherosclerosis pathogenesis and the protective role of ghrelin.