Title:Cellular Repressor of E1A-stimulated Genes, A New Potential Therapeutic Target for Atherosclerosis
Volume: 18
Issue: 15
关键词:
动脉粥样硬化,自噬,E1A刺激基因的细胞阻遏物,溶酶体,冠状动脉疾病,中风
摘要: Background: Atherosclerosis is a chronic inflammatory disease and a major risk factor for
several important cardiovascular events, particularly coronary artery disease and stroke. The pathological
process of atherosclerosis is considered to be dynamic and complicated, involving interactions between
various different cell types within arteries and the cells that migrate into the vessel wall.
Objective: Human cellular repressor of E1A-stimulated genes (CREG) was originally identified as a transcription
factor with the ability to antagonize transcriptional activation and cellular transformation induced
by the adenovirus E1A oncoprotein. However, subsequent studies also identified it as a secreted glycoprotein
able to sustain cellular homeostasis and withstand pathological cell and tissue damage.
Results: We demonstrated that CREG may modulate homeostasis of vascular wall cells and inhibit
inflammation of vascular tissue cells and macrophages, indicating a potential protective effect of
CREG against inflammation. Mechanistically, CREG behaves like a typical soluble lysosomal protein
that regulates the formation and maturation of lysosomes by modulating the small GTPase protein
Rab7, to mediate autophagy in vascular tissue cells.
Conclusion: The impact of CREG on lysosome formation may have important therapeutic significance
in atherosclerosis.