PP2A alleviates oxidized LDL-induced endothelial dysfunction by regulating LOX-1/ROS/MAPK axis

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Cellular Signaling

Background:

• Atherosclerosis (AS) involves endothelial dysfunction.
• Oxidized low-density lipoprotein (Ox-LDL) is a key contributor to AS.
• The role of protein phosphatase 2A (PP2A) in AS progression requires elucidation.

Purpose of the Study:

• To investigate the effect of PP2A on AS progression.
• To identify the molecular mechanisms underlying PP2A's action in AS.

Main Methods:

• Assessed PP2A expression in human umbilical vein endothelial cells (HUVECs) exposed to Ox-LDL using RT-PCR and Western blot.
• Determined PP2A and LOX-1 binding via Co-immunoprecipitation (CoIP).
• Measured VCAM-1, ICAM-1, and MCP-1 protein levels via Western blot.

Main Results:

• PP2A expression decreased with increasing Ox-LDL concentration in HUVECs.
• PP2A overexpression mitigated Ox-LDL-induced HUVEC dysfunction and inflammation.
• PP2A directly interacted with and inhibited LOX-1 expression.
• PP2A inhibited the LOX-1/ROS/MAPK signaling axis.

Conclusions:

• PP2A alleviates Ox-LDL-induced endothelial dysfunction and inflammation by regulating the LOX-1/ROS/MAPK axis.
• PP2A exhibits anti-inflammatory effects in AS development.
• PP2A represents a potential molecular therapeutic target for AS.