Retraction Note to: “Sodium Ferulate Inhibits High-Fat Diet-Induced Inflammatory Factors Expression in Human Umbilical Vein Endothelial Cells”

Irisin is a novel hormone secreted by myocytes. Lower levels of irisin are independently associated with endothelial dysfunction in obese subjects. The objective of this study was to explore whether irisin exerts a direct vascular protective effect on endothelial function in high-fat-diet-induced obese mice. Male C57BL/6 mice were given chow or a high-fat diet with or without treatment with irisin. Aortic endothelial function was determined by measuring endothelium-dependent vasodilatation (EDV). Nitric oxide (NO) in the aorta was determined. The effect of irisin on the levels of AMP-activated protein kinase (AMPK), Akt, and endothelial NO synthase (eNOS) phosphorylation in endothelial cells was determined. Human umbilical vein endothelial cells were used to study the role of irisin in the AMPK-eNOS pathway. Acetylcholine-stimulated EDV was significantly lower in obese mice compared with control mice. Treatment of obese mice with irisin significantly enhanced EDV and improved endothelial function. This beneficial effect of irisin was partly attenuated in the presence of inhibitors of AMPK, Akt, and eNOS. Treatment of obese mice with irisin enhanced NO production and phosphorylation of AMPK, Akt, and eNOS in endothelial cells. These factors were also enhanced by irisin in human umbilical vein endothelial cells in vitro. Suppression of AMPK expression by small interfering RNA blocked irisin-induced eNOS and Akt phosphorylation and NO production. We have provided the first evidence that irisin improves endothelial function in aortas of high-fat-diet-induced obese mice. The mechanism for this protective effect is related to the activation of the AMPK-eNOS signaling pathway.

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CTRP3 Protects against High Glucose-Induced Cell Injury in Human Umbilical Vein Endothelial Cells

Analytical Cellular Pathology ◽

10.1155/2019/7405602 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Fang Wang ◽

Linlin Zhao ◽

Yingguang Shan ◽

Ran Li ◽

Guijun Qin

Keyword(s):

Endothelial Cells ◽

Endothelial Dysfunction ◽

High Glucose ◽

Cell Injury ◽

Umbilical Vein ◽

Cell Loss ◽

Inflammatory Factors ◽

Therapeutic Drug ◽

Human Umbilical Vein ◽

Umbilical Vein Endothelial Cells

Aims. Inflammation was closely associated with diabetes-related endothelial dysfunction. C1q/tumor necrosis factor-related protein 3 (CTRP3) is a member of the CTRP family and can provide cardioprotection in many cardiovascular diseases via suppressing the production of inflammatory factors. However, the role of CTRP3 in high glucose- (HG-) related endothelial dysfunction remains unclear. This study evaluates the effects of CTRP3 on HG-induced cell inflammation and apoptosis. Materials and Methods. To prevent high glucose-induced cell injury, human umbilical vein endothelial cells (HUVECs) were pretreated with recombinant CTRP3 for 1 hour followed by normal glucose (5.5 mmol/l) or high glucose (33 mmol/l) treatment. After that, cell apoptosis and inflammatory factors were determined. Results. Our results demonstrated that CTRP3 mRNA and protein expression were significantly decreased after HG exposure in HUVECs. Recombinant human CTRP3 inhibited HG-induced accumulation of inflammatory factors and cell loss in HUVECs. CTRP3 treatment also increased the phosphorylation levels of protein kinase B (AKT/PKB) and the mammalian target of rapamycin (mTOR) in HUVECs. CTRP3 lost its inhibitory effects on HG-induced cell inflammation and apoptosis after AKT inhibition. Knockdown of endogenous CTRP3 in HUVECs resulted in increased inflammation and decreased cell viability in vitro. Conclusions. Taken together, these findings indicated that CTRP3 treatment blocked the accumulation of inflammatory factors and cell loss in HUVECs after HG exposure through the activation of AKT-mTOR signaling pathway. Thus, CTRP3 may be a potential therapeutic drug for the prevention of diabetes-related endothelial dysfunction.

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GPR55 Antagonist CID16020046 Protects against Atherosclerosis Development in Mice by Inhibiting Monocyte Adhesion and Mac-1 Expression

International Journal of Molecular Sciences ◽

10.3390/ijms222313084 ◽

2021 ◽

Vol 22 (23) ◽

pp. 13084

Author(s):

Seung-Jin Lee ◽

Dong-Soon Im

Keyword(s):

Endothelial Cells ◽

High Fat Diet ◽

Vascular Endothelial Cells ◽

Umbilical Vein ◽

Vascular Endothelial ◽

Monocyte Adhesion ◽

High Fat ◽

Potent Agonist ◽

Atherosclerosis Development ◽

Umbilical Vein Endothelial Cells

GPR55 recognizes several lipid molecules such as lysophosphatidylinositol. GPR55 expression was reported in human monocytes. However, its role in monocyte adhesion and atherosclerosis development has not been studied. The role of GPR55 in monocyte adhesion and atherosclerosis development was investigated in human THP-1 monocytes and ApoE−/− mice using O-1602 (a potent agonist of GPR55) and CID16020046 (a specific GPR55 antagonist). O-1602 treatment significantly increased monocyte adhesion to human umbilical vein endothelial cells, and the O-1602-induced adhesion was inhibited by treatment with CID16020046. O-1602 induced the expression of Mac-1 adhesion molecules, whereas CID16020046 inhibited this induction. Analysis of the promoter region of Mac-1 elucidated the binding sites of AP-1 and NF-κB between nucleotides −750 and −503 as GPR55 responsive elements. O-1602 induction of Mac-1 was found to be dependent on the signaling components of GPR55, that is, Gq protein, Ca2+, CaMKK, and PI3K. In Apo−/− mice, administration of CID16020046 ameliorated high-fat diet-induced atherosclerosis development. These results suggest that high-fat diet-induced GPR55 activation leads to the adhesion of monocytes to endothelial cells via induction of Mac-1, and CID16020046 blockage of GPR55 could suppress monocyte adhesion to vascular endothelial cells through suppression of Mac-1 expression, leading to protection against the development of atherosclerosis.

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GPR55 antagonist CID16020046 protects against atherosclerosis development in mice by inhibiting monocyte adhesion and Mac-1 expression

10.22541/au.163290912.29610111/v1 ◽

2021 ◽

Author(s):

Seung-Jin Lee ◽

DONG-SOON IM

Keyword(s):

Endothelial Cells ◽

High Fat Diet ◽

Vascular Endothelial Cells ◽

Umbilical Vein ◽

Monocyte Adhesion ◽

High Fat ◽

Atherosclerosis Development ◽

Proinflammatory Role ◽

Umbilical Vein Endothelial Cells

Background and Purpose: GPR55 is a G protein-coupled receptor that recognizes several lipid molecules. GPR55 expression in human monocytes and its proinflammatory role lead us to investigate the role of GPR55 in monocyte adhesion and atherosclerosis development. Experimental Approach: We investigated monocyte adhesion in human THP-1 monocytes and atherosclerosis development in ApoE-/- mice by using O-1602 (a potent agonist of GPR55), CID16020046 (a specific GPR55 antagonist), and a high-fat diet-induced atherosclerosis model. Key Results: In human THP-1 monocytes, treatment with O-1602 signiﬁcantly increased monocyte adhesion to human umbilical vein endothelial cells (HUVECs), and the O-1602-induced adhesion was inhibited by treatment with CID16020046. O-1602 induced the expression of Mac-1 adhesion molecules, whereas CID16020046 inhibited this induction. Analysis of the promoter region of Mac-1 elucidated the binding sites of AP-1 and NF-κB between nucleotides -750 and -503 as GPR55 responsive elements. Furthermore, O-1602 induction of Mac-1 through AP-1 and NF-B was found to be dependent on the signaling components of GPR55, that is, Gq protein, Ca2+, CaMKK, and PI3K. In an in vivo study of high-fat diet-induced atherosclerosis in ApoE-/- mice, administration of CID16020046 ameliorated atherosclerosis development. These results suggest that high-fat diet-induced GPR55 activation leads to adhesion of monocytes to endothelial cells via induction of Mac-1, and CID16020046 blockage of GPR55 could suppress monocyte adhesion to vascular endothelial cells through suppression of Mac-1 expression, leading to protection against the development of atherosclerosis. Conclusions: This report suggests that GPR55 may be a therapeutic target for atherosclerosis development.

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