Atorvastatin inhibits CD68 expression in aortic root through a GRP78-involved pathway

Area of Science:

• Endocrinology and Metabolism
• Cardiovascular Research
• Cellular Biology

Background:

• Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum chaperone.
• Statins, like atorvastatin, may influence ER stress by increasing GRP78 levels.
• Atherosclerosis involves ER stress and macrophage infiltration.

Purpose of the Study:

• To investigate if atorvastatin's anti-atherosclerotic effects are mediated by a pathway involving GRP78.
• To explore the role of GRP78 in modulating macrophage activity in atherosclerosis.

Main Methods:

• Diabetic hamsters received varying doses of atorvastatin; aortic roots were examined for GRP78 and CD68 expression.
• THP-1 macrophages were treated with glucose and atorvastatin in vitro, with GRP78 and CD68 levels assessed.
• The effect of a GRP78 inhibitor (deoxynivalenol) on atorvastatin's impact on CD68 was evaluated in vitro.

Main Results:

• Atorvastatin significantly reduced macrophage infiltration and CD68 expression in hamster aortic roots.
• Atorvastatin treatment increased GRP78 expression in vivo and in vitro.
• In vitro, atorvastatin's suppression of CD68 was reversed by a GRP78 inhibitor, indicating GRP78 mediation.

Conclusions:

• Atorvastatin inhibits CD68 expression via GRP78 regulation, suggesting a novel anti-atherosclerosis mechanism.
• GRP78 plays a protective role in early atherosclerosis, extending beyond its chaperone function.
• This research offers new insights into the therapeutic actions of atorvastatin in preventing atherosclerosis.