The relationship with the stability between GRP78, CHOP and human carotid atherosclerotic plaque

Background: Current researches on human carotid atherosclerosis (AS) plaques are focused on vulnerable plaques, and various methods have been clinically used to detect vulnerable plaques to prevent adverse events. GRP78 and CHOP, as markers in the endoplasmic reticulum stress (ERS), have a certain relationship with the stability of plaque tissue.

Methods: In this study, 150 plaque specimens were obtained from carotid endarterectomy (CEA). According to pathology, they were divided into two groups: stable plaque and vulnerable plaque. Immunohistochemistry was used to semi-quantitate and localize the target molecule. Western blot and RT-qPCR were used to detect the expression of GRP78 and CHOP in the samples. The receiver operating characteristic curve (ROC curve) judges the significance of the target molecule as a biomarker for the diagnosis of vulnerable plaques.

Results: The results of immunohistochemistry showed that the target molecules of GRP78 and CHOP were mainly expressed in inflammatory cells and vascular endothelial cells; Western blot and RT-qPCR techniques were used to detect the expression of GRP78 and CHOP in different pathlogical types of plaques, which respectively indicated that there were differential expressions. The expression in vulnerable plaques was significantly higher than that in stable plaques (P < 0.05). analysis with ROC, the areas under curves (AUC) of the GRP78 and CHOP data were calculated as 0.792 and 0.850, respectively and the combination showed the largest AUC of 0.870.

Conclusion: In endoplasmic reticulum stress, GRP78 and CHOP are significantly higher expressions in vulnerable plaques than stable's, which indicated that GRP78 and CHOP played a certain role in the occurrence and development of human carotid atherosclerosis and vulnerable plaques; GRP78 and CHOP are promising molecular biomarkers for identifying the endoplasmic reticulum stress situation, atherosclerosis and plaque stability. They also could provide a potential drug targets for the prevention and treatment of atherosclerosis.