Cellular Repressor of E1A-stimulated Genes, A New Potential Therapeutic Target for Atherosclerosis.

Abstract

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. 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. 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. The impact of CREG on lysosome formation may have important therapeutic significance in atherosclerosis.