| 1. |
- Hirschberg, Daniel, et al.
(author)
-
Identification of endothelial proteins by MALDI-MS using a compact disc microfluidic system.
- 2004
-
In: The Protein Journal. - 1572-3887 .- 1875-8355. ; 23:4
-
Journal article (peer-reviewed)abstract
- Vascular endothelial proteins have been analyzed using two-dimensional (2D) gel electrophoresis and subsequent mass spectrometry, with separate methods for the intervening sample preparations. Compact disc (CD) technology was found to be rapid, giving high overall yield both with ordinary Coomassie staining and with Sypro Ruby staining. Combined with automatic in-gel digestion, the CD technology has great capacity for large numbers of protein analysis, although for limited sample numbers, manual methods can give similar sequence coverage. In a test set of 48 samples, 45 proteins were identified using the CD preparation technique, 32 identified with higher sequence coverage using the CD technique, 7 with higher using ZipTips in a robotic workstation, and 5 with higher coverage using dried droplets of unpurified samples. In the process of these methodological comparisons, basic patterns for 116 endothelial proteins were defined, representing 297 separate protein spots on the 2D gels.
|
|
| 2. |
- Mälarstig, Anders, et al.
(author)
-
Variants of the interferon regulatory factor 5 gene regulate expression of IRF5 mRNA in atherosclerotic tissue but are not associated with myocardial infarction
- 2008
-
In: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 28:5, s. 975-982
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Signaling events after activation of toll-like receptors (TLRs) are important mechanisms promoting inflammation in the atherosclerotic plaque. INF regulatory factor 5 (IRF5) is one of the mediators of downstream effects of TLRs. Several single nucleotide polymorphisms (SNPs) in the IRF5 gene have been found to be associated with systemic lupus erythematosus. METHODS AND RESULTS: We examined IRF5 mRNA expression in carotid atherosclerotic tissue (n=99) and the case-control association between SNPs in the IRF5 gene with myocardial infarction (MI) (n=376+387) and unstable coronary artery disease (CAD) (n=3101+445). Among unstable CAD patients, association of IRF5 SNPs with recurrent coronary events (n=401) was also investigated. The IRF5 mRNA expression was increased in atherosclerotic tissue compared with control tissue (P<0.001). Significant associations with IRF5 expression was observed for 6 of 10 SNPs in the study. However, the IRF5 SNPs examined were neither associated with the risk of precocious MI, nor with unstable CAD or risk of recurrent cardiovascular events in unstable CAD patients. CONCLUSIONS: IRF5 mRNA is expressed in cells in atherosclerotic tissue and its expression is modified by SNPs in the IRF5 gene. Genetic variation at the IRF5 locus was, however, not associated with CAD or related phenotypes.
|
|
| 3. |
- Olofsson, Peder S., et al.
(author)
-
CD137 is expressed in human atherosclerosis and promotes development of plaque inflammation in hypercholesterolemic mice
- 2008
-
In: Circulation. - Baltimore, Md. : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 117:10, s. 1292-1301
-
Journal article (peer-reviewed)abstract
- Background— Atherosclerosis is a multifactorial disease in which inflammatory processes play an important role. Inflammation underlies lesion evolution at all stages, from establishment to plaque rupture and thrombosis. Costimulatory molecules of the tumor necrosis factor superfamily such as CD40/CD40L and OX40/OX40L have been implicated in atherosclerosis. Methods and Results— This study shows that the tumor necrosis factor superfamily members CD137 and CD137 ligand (CD137L), which play a major role in several autoimmune diseases, may constitute a pathogenic pair in atherogenesis. We detected CD137 protein in human atherosclerotic lesions not only on T cells but also on endothelial cells and showed that CD137 in cultured endothelial cells and smooth muscle cells was induced by proinflammatory cytokines implicated in atherosclerosis. Activation of CD137 by CD137L induced adhesion molecule expression on endothelial cells and reduced smooth muscle cell proliferation. In addition, treatment of atherosclerosis-prone apolipoprotein E–deficient mice with a CD137 agonist caused increased inflammation. T-cell infiltration, mainly of CD8+ cells, and expression of the murine major histocompatibility complex class II molecule I-Ab increased significantly in atherosclerotic lesions, as did the aortic expression of proinflammatory cytokines. Conclusions— Taken together, these observations suggest that CD137-CD137L interactions in the vasculature may contribute to the progression of atherosclerosis via augmented leukocyte recruitment, increased inflammation, and development of a more disease-prone phenotype.
|
|
| 4. |
- Olofsson, Peder, et al.
(author)
-
The antiviral cytomegalovirus inducible gene 5/viperin is expressed in atherosclerosis and regulated by proinflammatory agents
- 2005
-
In: Arteriosclerosis, Thrombosis and Vascular Biology. - : American Heart Association. - 1079-5642 .- 1524-4636. ; 25:7, s. 113-116
-
Journal article (peer-reviewed)abstract
- OBJECTIVE:Inflammatory processes play an important role in atherosclerosis, and increasing evidence implies that microbial pathogens and proinflammatory cytokines are involved in the development and activation of atherosclerotic lesions. To find new inflammatory genes, we explored the vascular transcriptional response to an activator of innate immunity bacterial lipopolysaccharides (LPSs).METHODS AND RESULTS:Gene arrays identified the cytomegalovirus-inducible gene 5 (cig5)/viperin among the genes most potently induced by LPS in human vascular biopsies. Viperin was expressed by endothelial cells in atherosclerotic arteries and significantly elevated in atherosclerotic compared with normal arteries. In culture, cytomegalovirus infection, interferon-gamma, and LPS induced viperin expression.CONCLUSIONS:Viperin is expressed in atherosclerosis and induced in vascular cells by inflammatory stimuli and cytomegalovirus infection. The putative functions of viperin in atherosclerosis may relate to disease-associated microbes.
|
|
| 5. |
- Swedenborg, Jesper, et al.
(author)
-
Symtomgivande karotisstenos bör opereras, inte behandlas med stent : Stent ger för stora risker, enligt studier
- 2007
-
In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 104:6, s. 412-414
-
Journal article (peer-reviewed)abstract
- [Symptomatic carotid stenosis should be treated surgically, not with stenting. Great risks with stents, according to studies] The benefit of addition carotid endarterectomy to best medical treatment for stroke prevention has been proven for both symptomatic and asymptomatic severe carotid stenosis. During recent years endovascular treatment of carotid stenosis has grown. A meta analysis of five trials published 2005 concluded that carotid artery stenting should only be done within the framework of ongoing studies and that the evidence base was lacking to change routine treatment from carotid endarterectomy to carotid artery stenting. Recently two large studies, stent supported percutaneous angioplasty of the carotid artery versus endarterectomy (SPACE) and endarterectomy versus angioplasty in patients with symptomatic severe carotid stenosis (EVA-3S) have been published. Both studies tested the hypothesis of non-inferiority of carotid artery stenting compared to carotid endarterectomy. EVA-3S was terminated prematurely because of significantly inferior results for carotid stenting, both at 30 days and 6 months. The combined incidence of stroke or death was 9.6 % in the stented group and 3.9 in the operated group and 6.1 % and 11.7 % respectively at 6 months. All differences were highly significant. In the SPACE trial non-inferiority could not be shown. Based on intention to treat no significant difference in outcome for the primary end point, ipsilateral ischaemic stroke or death within 30 days could be shown. Analyses per protocol, however, revealed a significant difference for ipsilateral stroke at 30 days, 6.95 % versus 5.64 % in the stented and the operated group respectively. SPACE did not report any long term results. Based on available evidence it is concluded that carotid artery stenting should not be performed outside ongoing randomised trials.
|
|
| 6. |
- Tran-Lundmark, Karin, et al.
(author)
-
Heparan sulfate in perlecan promotes mouse atherosclerosis: roles in lipid permeability, lipid retention, and smooth muscle cell proliferation.
- 2008
-
In: Circulation research. - 1524-4571. ; 103:1, s. 43-52
-
Journal article (peer-reviewed)abstract
- Heparan sulfate (HS) has been proposed to be antiatherogenic through inhibition of lipoprotein retention, inflammation, and smooth muscle cell proliferation. Perlecan is the predominant HS proteoglycan in the artery wall. Here, we investigated the role of perlecan HS chains using apoE null (ApoE0) mice that were cross-bred with mice expressing HS-deficient perlecan (Hspg2(Delta3/Delta3)). Morphometry of cross-sections from aortic roots and en face preparations of whole aortas revealed a significant decrease in lesion formation in ApoE0/Hspg2(Delta3/Delta3) mice at both 15 and 33 weeks. In vitro, binding of labeled mouse triglyceride-rich lipoproteins and human LDL to total extracellular matrix, as well as to purified proteoglycans, prepared from ApoE0/Hspg2(Delta3/Delta3) smooth muscle cells was reduced. In vivo, at 20 minutes influx of human (125)I-LDL or mouse triglyceride-rich lipoproteins into the aortic wall was increased in ApoE0/Hspg2(Delta3/Delta3) mice compared to ApoE0 mice. However, at 72 hours accumulation of (125)I-LDL was similar in ApoE0/Hspg2(Delta3/Delta3) and ApoE0 mice. Immunohistochemistry of lesions from ApoE0/Hspg2(Delta3/Delta3) mice showed decreased staining for apoB and increased smooth muscle alpha-actin content, whereas accumulation of CD68-positive inflammatory cells was unchanged. We conclude that the perlecan HS chains are proatherogenic in mice, possibly through increased lipoprotein retention, altered vascular permeability, or other mechanisms. The ability of HS to inhibit smooth muscle cell growth may also influence development as well as instability of lesions.
|
|
| 7. |
- Wassélius, Johan, et al.
(author)
-
High 18F-FDG Uptake in synthetic aortic vascular grafts on PET/CT in symptomatic and asymptomatic patients
- 2008
-
In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 49:10, s. 1601-5
-
Journal article (peer-reviewed)abstract
- Graft infection is a serious complication to vascular surgery. The aim of this study was to assess (18)F-FDG uptake in vascular grafts in patients with or without symptoms of graft infection. METHODS: In all 2,045 patients examined by PET/CT at our clinic, 16 patients with synthetic aortic grafts were identified and reevaluated for (18)F-FDG accumulation. Clinical and biochemical data were obtained from patient records. RESULTS: High (18)F-FDG uptake was found in 10 of 12 grafts in the patients who underwent open surgery and in 1 of 4 grafts in patients who underwent endovascular aneurysm repair. On the basis of biochemical and clinical data, it was concluded that 1 of the 16 patients had a graft infection at the time of investigation. CONCLUSION: (18)F-FDG uptake in vascular grafts was found in the vast majority of patients without graft infection. The risk of a false-positive diagnosis of graft infection by (18)F-FDG PET/CT is evident.
|
|
| 8. |
- Wuttge, Dirk M., et al.
(author)
-
CXCL16/SR-PSOX is an interferon-gamma-regulated chemokine and scavenger receptor expressed in atherosclerotic lesions
- 2004
-
In: Arteriosclerosis, Thrombosis and Vascular Biology. - : American Heart Association. - 1079-5642 .- 1524-4636. ; 24:4, s. 750-755
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Atherosclerosis is an inflammatory disease. Several chemokines are important for monocyte/macrophage and T-cell recruitment to the lesion. CXCL16 is a recently discovered chemokine that is expressed in soluble and transmembrane forms, ligates CXCR6 chemokine receptor, and guides migration of activated Th1 and Tc1 cells. It is identical to scavenger receptor SR-PSOX, which mediates uptake of oxidized low-density lipoprotein. We investigated whether CXCL16 expression is controlled by interferon-gamma (IFN-gamma)-cytokine abundant in atherosclerotic lesions. METHODS AND RESULTS: CXCL16 and CXCR6 expression was identified by polymerase chain reaction and histochemistry in atherosclerotic lesions from humans and apolipoprotein-E-deficient mice. In vitro IFN-gamma induced CXCL16 in human monocytic THP-1 cells and primary human monocytes, which led to increased uptake of oxidized low-density lipoprotein in THP-1 cells, which could be blocked by peptide antibodies against CXCL16. In vivo IFN-gamma induced CXCL16 expression in murine atherosclerotic lesions. CONCLUSIONS: We demonstrate a novel role of IFN-gamma in foam cell formation through upregulation of CXCL16/SR-PSOX. CXCR6 expression in the plaque confirms the presence of cells able to respond to CXCL16. Therefore, this chemokine/scavenger receptor could serve as a molecular link between lipid metabolism and immune activity in the atherosclerotic lesion.
|
|
