Objectives: This study aims to explore the molecular mechanisms of the protein subunit of complement I (C1q) tumor necrosis factor (TNF) related protein 1 (CTRP1) in the development of carotid plaque.Methods: An injury model and a CTRP1 over-expression model of high-glucose and high-lipid human umbilical vein endothelial cells (HUVECs) were constructed in vitro. The expression levels of inflammatory factors, tumor necrosis factor-alpha (TNF-alpha), human interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6), of all the groups, were detected by enzyme-linked immunosorbent assay (ELISA), and the gene expression levels of CTRP1, AMP-activated protein kinase (AMPK) and matrix metalloproteinase-9 (MMP-9) were detected by quantitative polymerase chain reaction (qPCR). The over-expressed CTRP1 with carotid plaque mouse model (CTRP1 + CAS) and carotid plaque mouse model (CAS) were established. The content of CTRP1 in serum and downstream AMPK, MMP-9, as well as inflammatory factors, were determined by ELISA. Mice in each group were biochemically examined for lipid indexes, including levels of triglycerides (TG), serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). CTRP1 knockout C57BL/6 mouse model was constructed. The levels of inflammatory factors, TNF-alpha, IL-1 beta and IL-6, in serum and the molecular levels of CTRP1/AMPK/MMP-9 in mice of each group were detected by ELISA. Biochemical assays were conducted to detect the blood lipid indexes of mice in each group, including the levels of TC, TG, LDL-C and HDL-C.Results: The results of ELISA on the in vitro and in vivo CAS models showed that in the serum of the model group, the expressions of TNF-alpha, IL-1 beta and IL-6 were up-regulated (*p < 0.05). The expression of CTRP1 was down-regulated (*p < 0.05), that of AMPK was also down-regulated (*p < 0.05) and that of MMP-9 was up-regulated (*p < 0.05) compared with the controls. The results of ELISA on the in vitro and in vivo CTRP1 + CAS models showed that compared with the ApoE knockout group, the levels of inflammatory factors (TNF-alpha, IL-1 beta and IL-6) in the CTRP1 + ApoE knockout group were significantly down-regulated (*p < 0.05).Conclusions: As an upstream molecule of a signaling pathway, CTRP1 can activate the AMPK signaling pathway, regulate the expressions of molecules such as AMPK and MMP-9, reduce the level of inflammatory factors (TNF-alpha, IL-1 beta and IL-6), drive the development of blood lipid indexes to the normal direction, and has a potential protective role in the occurrence and development of carotid plaque.
