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ObjectiveTo explore the underlying mechanism of bile acids and metabolites as well as the key metabolic pathways and important endogenous targets in prehypertension. MethodThe metabolic mechanism of prehypertension was explored with non-targeted metabolomics combined with network analysis. The serum metabolomics of patients with prehypertension was analyzed by ultra-high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry. The relevant biological functions and signal targets were predicted and generated by network analysis. Finally，the predicted targets of this important pathway were verified by in vitro experiments，and the relevant information was verified by enzyme-linked immunosorbent assay （ELISA） and Western blot. ResultAs revealed by non-targeted metabolomics，there were 64 potential biomarkers and 13 metabolic pathways in the normal group，the prehypertension group， and the hypertension group. The results of network analysis and biological verification showed that the occurrence of prehypertension was related to vascular inflammation caused by the abnormal metabolism of bile acids and aromatic amino acids. Bile acid metabolism plays an important role in the occurrence and development of prehypertension by regulating the vascular inflammatory response. Amino acid N-acyltransferase，myeloperoxidase， and bile acid downstream receptor TGR5 are critical in the changes of the metabolic network. ConclusionIn prehypertension，bile acids are presumedly involved in regulating vascular inflammation， resulting in damage to blood vessels in prehypertension.
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Abstract It has been reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces endothelial inflammation, therefore facilitating the progression of endothelial and vascular dysfunction in coronavirus disease 2019 (COVID-19) patients. Coronary artery bypass grafting (CABG) involves mainly the use of the saphenous vein (SV) and internal mammary artery as graft material in the stenosed coronary arteries. Unfortunately, graft patency of the SV is low due to endothelial dysfunction and inflammation. We propose that SARS-CoV-2 might cause vascular inflammation, endothelial dysfunction, and thrombosis in coronary artery bypass graft vessels by binding angiotensin-converting enzyme 2 receptor. Therefore, in this Special Article, we consider the potential influence of COVID-19 on the patency rates of coronary artery bypass graft vessels, mainly with reference to the SV. Moreover, we discuss the technique of SV graft harvesting and the therapeutic potential of focusing on endothelial dysfunction, vascular inflammation, and thrombosis for protecting coronary artery bypass grafts in COVID-19 infected CABG patients.
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Humans , Vascular Patency , Coronary Artery Bypass , Coronavirus Infections/complications , Graft Occlusion, Vascular/virology , Saphenous Vein/surgery , Thrombosis/physiopathology , Endothelium, Vascular/physiopathology , Treatment Outcome , Betacoronavirus , Inflammation/physiopathologyABSTRACT
Objective:Immune cells and inflammatory mediators play important roles in the development of atherosclerotic vascular inflammation.This study focuses on the direct effect ofIL-27 on human coronary artery endothelial cells.Methods:In this study,the effects of IL-27 and TNF-α on inflammatory cytokines and chemokines were investigated.Results:IL-27 could significantly enhance the TNF-α-mediated upregulation of inflammatory cytokine IL-6 and chemokines CCL5 from human coronary artery endothelial cells.The release of IL-6 and CCL5 was significantly suppressed by specific signaling molecule inhibitors.Conclusion:The induction of these mediators from the human coronary artery endothelial cells could be differentially regulated by the c-Jun N-terminal kinase,p38 mitogen-activated protein kinase,and nuclear factor-κB pathways.These results provided new insights into the effect of IL-27 on the TNF-α mediated activation of human coronary artery endothelial cells in atherosclerotic vascular inflammation.
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AIM:To investigate the role of immunoproteasome subunit β2i in deoxycorticosterone acetate (DOCA)/salt-induced vascular inflammation in mice.METHODS:Wild-type and β2i knockout male mice were used.The right kidney was removed and DOCA pellet was subcutaneously implanted in the mice.The mice were then received 1% NaCl as drinking water for 3 weeks.The total RNA and protein were isolated from thoracic aorta 3 weeks later.The aortic tissues were fixed in formalin, embedded in paraffin and sectioned.Western blot, real-time PCR and immunohistochemistry were performed to detect the expression of β2i, macrophage marker Mac-2, NF-κB, and proinflammatory cytokines IL-1β, IL-6 and TNF-α in thoracic aorta.RESULTS:Compared with sham group, DOCA/salt treatment significantly increased the expression of β2i at mRNA and protein levels, increased the infiltration of macrophages and expression of Mac-2, and upregulated the expression of NF-κB and proinflammatory cytokines including IL-1β, IL-6 and TNF-α in wild-type group, whereas theses effects were markedly attenuated in β2i knockout mice.CONCLUSION:Immuneproteasome subunit β2i is involved in DOCA/salt-induced vascular inflammation through activation of NF-κB signaling in the mice.
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Objective To investigate the effects of endogenous sulfur dioxide(SO2) on pulmonary vascular inflammation in rats with monocrotaline (MCT)-induced pulmonary hypertension.Methods Thirty-two Wistar rats were randomly divided into 4 groups(n =8 for each group):control group,MCT group,MCT + L-aspartic acid-β-hydroxamate(HDX) group,and MCT + SO2 group.Rats in the MCT group,MCT + HDX group,and MCT + SO2 group were subcutaneously injected with MCT(60 mg/kg) on the first day.For rats in MCT + HDX group,HDX(25 mg/kg,on day 0,7 and 14) was given orally after injection of MCT; and rats in MCT + SO2 group were subcutaneously injected with the SO2 donor sodium sulfite/sodium bisulfate(Na2SO3/NaHSO3,and mole ratio was adjusted to approximately 3:1) each day.Rats in the control group received only the same volume of solvent vehicle only.After 3 weeks,mean pulmonary artery pressure(mPAP) of each rat was evaluated by using a right cardiac catheterization procedure.Immunohistochemistry was used to detect the expression of inflammatory related factor intercellular adhesion molecule-1 (ICAM-1) and the key molecules of nuclear factor-κB (NF-κB) signal transduction pathway,including p65 and inhibitor of NF-κB (IκBα) in the small pulmonary artery endothelial cells.Results The differences in mPAP,expression of ICAM-1,IκBα and p65 in the small pulmonary artery endothelial cells were found among the 4 groups (mPAP:F =53.334,P ＜ 0.01 ; ICAM-1:F =183.82,P ＜ 0.01 ; IκBα:F =142.89,P ＜ 0.01 ; p65:F =105.46,P ＜0.01).The mean pulmonary artery pressure(mPAP) was significantly raised in MCT group rats as compared with that of the control group along with upregulated expressions of ICAM-1 protein and p65 protein in small pulmonary artery endothelial cells,while the expression of IκBα protein in small pulmonary artery endothelial cells was significantly low.After administration of HDX,the mPAP and the expression of ICAM-1 protein and p65 protein in small pulmonary artery endothelial cells further increased compared with those of MCT group,while the expression of IκBα protein in small pulmonary artery endothelial cells was significantly lower than that of MCT group.Whereas with treatment of SO2 derivatives,the mPAP,the expression of ICAM-1 protein and p65 protein in small pulmonary artery endothelial cells were significantly lower than those of MCT group,while the expression of IκBα protein in small pulmonary artery endothelial cells increased significantly compared with that of MCT group.Conclusions Endogenous SO2 might inhibit the activation of NF-κB pathway in the small pulmonary artery endothelial cells,attenuate the pulmonary vascular inflammation and prevent the MCT-induced pulmonary hypertension in rats.
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Matrix metalloproteinases (MMP),which are secreted by a variety of cell types,have the function of degrading extracellular matrix.Based on the substrate specificity,MMP can be assigned to five subgroups:interstitial collagenases,gelatinases,stromelysins,membrane-type MMP and others.MMP have been implicated in the pathophysiologic processes of tumor invasion and metastasis,angiogenesis,cardiovascular disease,etc.And emerging evidences have shown that MMP play important roles in vascular inflammation.
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Objective To study the relationship between the expression of peroxisome proliferator-activated receptor? (PPAR?) mRNA and the severity of coronary lesions in coronary heart disease(CHD) patients. Methods 153 patients with CHD who had undergone coronary angiography were admitted, the expression of PPAR? mRNA in peripheral lymphocytes was assessed using RT-PCR. The severity of coronary artery lesions was analyzed, and the lesions of coronary artery were delineated. Results Compared with control, in CHD patients IRI BMI TC LDL-C were elevated and HDL-C decreased. Significant decrease in PPAR? mRNA was observed in CHD patients (0.40?0.12 vs 0.62?0.13, P