Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
1.
Vascul Pharmacol ; 125-126: 106634, 2020.
Article in English | MEDLINE | ID: mdl-31866461

ABSTRACT

Despite the advent of new-generation drug-eluting stents, in-stent restenosis remains a significant problem in patients with coronary artery disease. In- stent restenosis is defined as the gradual re-narrowing of a stented coronary artery lesion due to arterial damage with subsequent local inflammation of the vessel wall and excessive growth of the vascular smooth muscle cells (vSMCs). Four-and-a-half LIM-domain protein 2 (FHL2) is a scaffold protein involved in regulating vSMC function and inflammation. Previously we have demonstrated that FHL2 prevents vSMC proliferation in a murine carotid artery ligation model. However, the effect of FHL2 on the inflammatory response of the vSMCs is not investigated. Therefore, we studied the inflammatory response in the vessel wall of FHL2-deficient (-KO) mice after carotid artery ligation. We found that circulating cytokines and local macrophage infiltration in the ligated carotid vessels were increased in FHL2-KO mice after carotid artery ligation. Moreover, FHL2-KO vSMCs showed increased secretion of cytokines such as SDF-1α and RANTES, and enhanced activation of the NFκB pathway. Finally, we found that blocking the NFκB signalling pathway abrogated this pro-inflammatory state in FHL2-KO vSMCs. Taken together, our results demonstrate that FHL2 decreases the inflammatory response of vSMCs through inhibition of the NFkB-signalling pathway.


Subject(s)
Carotid Artery Diseases/metabolism , Inflammation/metabolism , LIM-Homeodomain Proteins/metabolism , Muscle Proteins/metabolism , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , NF-kappa B/metabolism , Transcription Factors/metabolism , Animals , Anti-Inflammatory Agents/pharmacology , Carotid Arteries/metabolism , Carotid Arteries/pathology , Carotid Artery Diseases/genetics , Carotid Artery Diseases/pathology , Carotid Artery Diseases/prevention & control , Cells, Cultured , Cytokines/blood , Disease Models, Animal , Inflammation/genetics , Inflammation/pathology , Inflammation/prevention & control , LIM-Homeodomain Proteins/deficiency , LIM-Homeodomain Proteins/genetics , Macrophages/metabolism , Macrophages/pathology , Mice, Knockout , Muscle Proteins/deficiency , Muscle Proteins/genetics , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/pathology , NF-kappa B/antagonists & inhibitors , NF-kappa B/genetics , Signal Transduction , Transcription Factors/deficiency , Transcription Factors/genetics
3.
Colloids Surf B Biointerfaces ; 141: 365-373, 2016 May 01.
Article in English | MEDLINE | ID: mdl-26878287

ABSTRACT

The role of biomaterials surface in controlling the interfacial biological events leading to implant integration is of key importance. In this study, the effects of NiTi surfaces treated by plasma electrolytic oxidation (PEO) on human umbilical vein endothelial cells (HUVECs) have been investigated. The changes in NiTi surface morphology and chemistry were assessed by SEM, XPS and cross-section TEM/EDX analyzes whereas the effects of the resultant surfaces on in vitro endothelialization and cell junction proteins have been evaluated by life/dead staining, SEM, cells counting, qPCR and immunofluorescence. The findings indicated that the PEO-treated NiTi, with a microporous morphology and oxide dominated surface chemistry, supports viability and proliferation of HUVECs. Numerous thin filopodia probing the microporous surface assisted cells attachment. In addition, claudin-5 and occludin have been upregulated and expression of vascular endothelial-cadherin was not suppressed on PEO-treated NiTi relative to the reference electropolished surfaces. The results of this study suggest that novel NiTi surfaces may be developed using the PEO process, which can be of benefit to atherosclerosis treatment.


Subject(s)
Coated Materials, Biocompatible/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Nickel/pharmacology , Titanium/pharmacology , Alloys/chemistry , Alloys/pharmacology , Antigens, CD/genetics , Antigens, CD/metabolism , Cadherins/genetics , Cadherins/metabolism , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Claudin-5/genetics , Claudin-5/metabolism , Coated Materials, Biocompatible/chemistry , Electrolysis , Electrolytes/chemistry , Gene Expression/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells/ultrastructure , Humans , Microscopy, Confocal , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Nickel/chemistry , Occludin/genetics , Occludin/metabolism , Oxidation-Reduction , Photoelectron Spectroscopy , Reverse Transcriptase Polymerase Chain Reaction , Surface Properties , Titanium/chemistry
4.
Allergy ; 70(12): 1531-44, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26222912

ABSTRACT

BACKGROUND: Asthma is an inflammatory disease that involves airway hyper-responsiveness and mucus hypersecretion. The LIM-only protein FHL2 is a crucial modulator of multiple signal transduction pathways and functions as a scaffold in specific protein-protein interactions. OBJECTIVE: We sought to investigate the role of FHL2 in airway inflammation. METHODS: Allergic airway inflammation was induced in WT and FHL2-knock out (FHL2-KO) mice with ovalbumin (OVA). Lung tissue, bronchoalveolar lavage fluid (BALF) and draining lymph node cells were analysed for inflammation. FHL2 loss and gain of function studies were performed in lung epithelial cells. RESULTS: FHL2-deficient mice challenged with OVA show significantly reduced airway inflammation as evidenced by reduced infiltration of inflammatory cells including eosinophils, dendritic cells, B cells and T cells. Furthermore, mucus production was decreased in FHL2-KO mice. In BALF, the levels of IL-5, IL-13, eotaxin-1 and eotaxin-2 were significantly lower in FHL2-KO mice. In addition, draining lymph node cells from FHL2-KO mice show reduced levels of IL-5 and IL-13. Consistent with this, OVA-specific serum IgG and IgE levels were reduced in FHL2-KO mice. We also found that phosphorylation of ERK1/2 is markedly attenuated in FHL2-KO lung. Knock-down of FHL2 in human lung epithelial cells resulted in a striking decrease in ERK1/2 phosphorylation and mRNA levels of inflammatory cytokines and MUC5AC, whereas FHL2 overexpression exhibited opposite effects. Finally, the SNP rs4851765 shows an association with the severity of bronchial hyper-responsiveness. CONCLUSION: These results highlight functional involvement of FHL2 in airway inflammation and identify FHL2 as a novel gene associated with asthma severity in human.


Subject(s)
Asthma/genetics , LIM-Homeodomain Proteins/metabolism , Muscle Proteins/metabolism , Pneumonia/genetics , Respiratory Hypersensitivity/genetics , Transcription Factors/metabolism , Animals , Asthma/metabolism , Blotting, Western , Disease Models, Animal , Genetic Predisposition to Disease/genetics , Genotype , Humans , LIM-Homeodomain Proteins/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , Muscle Proteins/genetics , Oligonucleotide Array Sequence Analysis , Pneumonia/metabolism , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , Respiratory Hypersensitivity/metabolism , Transcription Factors/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...