
Asia Pacific Academy of Science Pte. Ltd. (APACSCI) specializes in international journal publishing. APACSCI adopts the open access publishing model and provides an important communication bridge for academic groups whose interest fields include engineering, technology, medicine, computer, mathematics, agriculture and forestry, and environment.

The Mechanism of CTRP1 Inhibiting the Formation of Carotid Plaque by Regulating the CTRP1/AMPK/MMP-9 Pathways
Vol 37, Issue 1, 2023
Abstract
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-α (TNF-α), human interleukin-1β (IL-1β) 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-α, IL-1β 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-α, IL-1β 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-α, IL-1β 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-α, IL-1β 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.
Keywords
References
Supporting Agencies
Copyright (c) 2023 Nannan Wang, Rui He, Li Fan, Jinxia Fu, Xiaoqiong Li, Guiling Li
This site is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Medical Genetics, University of Torino Medical School, Italy

Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy