共查询到20条相似文献,搜索用时 31 毫秒
1.
Akinori Hasegawa Kengo Sato Remina Shirai Rena Watanabe Keigo Yamamoto Kaho Watanabe Kyoko Nohtomi Tsutomu Hirano Takuya Watanabe 《PloS one》2014,9(12)
Aim
Atherosclerosis is the complex lesion that consists of endothelial inflammation, macrophage foam cell formation, vascular smooth muscle cell (VSMC) migration and proliferation, and extracellular matrix production. Human urocortin 1 (Ucn1), a 40-amino acid peptide member of the corticotrophin-releasing factor/urotensin I family, has potent cardiovascular protective effects. This peptide induces potent and long-lasting hypotension and coronary vasodilation. However, the relationship of Ucn1 with atherosclerosis remains unclear. The present study was performed to clarify the effects of Ucn1 on atherosclerosis.Methods
We assessed the effects of Ucn1 on the inflammatory response and proliferation of human endothelial cells (ECs), human macrophage foam cell formation, migration and proliferation of human VSMCs, extracellular matrix expression in VSMCs, and the development of atherosclerosis in apolipoprotein E-deficient (Apoe −/−) mice.Results
Ucn1 significantly suppressed cell proliferation without inducing apoptosis, and lipopolysaccharide-induced up-regulation of monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 in human ECs. Ucn1 significantly reduced oxidized low-density lipoprotein-induced foam cell formation with a significant down-regulation of CD36 and acyl-CoA:cholesterol acyltransferase 1 in human monocyte-derived macrophages. Ucn1 significantly suppressed the migration and proliferation of human VSMCs and increased the activities of matrix metalloproteinase-2 (MMP2) and MMP9 in human VSMCs. Intraperitoneal injection of Ucn1 into Apoe −/− mice for 4 weeks significantly retarded the development of aortic atherosclerotic lesions.Conclusions
This study provided the first evidence that Ucn1 prevents the development of atherosclerosis by suppressing EC inflammatory response and proliferation, macrophage foam cell formation, and VSMC migration and proliferation. Thus, Ucn1 could serve as a novel therapeutic target for atherosclerotic cardiovascular diseases. 相似文献2.
3.
Lim S Choi SH Shin H Cho BJ Park HS Ahn BY Kang SM Yoon JW Jang HC Kim YB Park KS 《PloS one》2012,7(4):e35007
Background
Recently, it has been suggested that enhancement of incretin effect improves cardiac function. We investigated the effect of a DPP-IV inhibitor, des-fluoro-sitagliptin, in reducing occurrence of restenosis in carotid artery in response to balloon injury and the related mechanisms.Methods and Findings
Otsuka Long-Evans Tokushima Fatty rats were grouped into four: control (normal saline) and sitagliptin 100, 250 and 500 mg/kg per day (n = 10 per group). Sitagliptin or normal saline were given orally from 1 week before to 2 weeks after carotid injury. After 3 weeks of treatment, sitagliptin treatment caused a significant and dose-dependent reduction in intima-media ratio (IMR) in obese diabetic rats. This effect was accompanied by improved glucose homeostasis, decreased circulating levels of high-sensitivity C-reactive protein (hsCRP) and increased adiponectin level. Moreover, decreased IMR was correlated significantly with reduced hsCRP, tumor necrosis factor-α and monocyte chemoattractant protein-1 levels and plasminogen activator inhibitor-1 activity. In vitro evidence with vascular smooth muscle cells (VSMCs) demonstrated that proliferation and migration were decreased significantly after sitagliptin treatment. In addition, sitagliptin increased caspase-3 activity and decreased monocyte adhesion and NFκB activation in VSMCs.Conclusions
Sitagliptin has protective properties against restenosis after carotid injury and therapeutic implications for treating macrovascular complications of diabetes. 相似文献4.
Anne Mette Fisker Hag Ulrik Sloth Kristoffersen Sune Folke Pedersen Henrik Gutte Anne-Mette Lebech Andreas Kjaer 《PloS one》2009,4(12)
Background
Increased prevalence of atherosclerotic cardiovascular disease in HIV-infected patients has been observed. The cause of this accelerated atherosclerosis is a matter of controversy. As clinical studies are complicated by a multiplicity of risk-factors and a low incidence of hard endpoints, studies in animal models could be attractive alternatives.Methodology/Principal Findings
We evaluated gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in HIV-1 transgenic (HIV-1Tg) rats; these genes are all thought to play important roles in early atherogenesis. Furthermore, the plasma level of sICAM-1 was measured. We found that gene expressions of LOX-1 and VCAM-1 were higher in the aortic arch of HIV-1Tg rats compared to controls. Also, the level of sICAM-1 was elevated in the HIV-1Tg rats compared to controls, but the ICAM-1 gene expression profile did not show any differences between the groups.Conclusions/Significance
HIV-1Tg rats have gene expression patterns indicating endothelial dysfunction and accelerated atherosclerosis in aorta, suggesting that HIV-infection per se may cause atherosclerosis. This transgenic rat model may be a very promising model for further studies of the pathophysiology behind HIV-associated cardiovascular disease. 相似文献5.
Tatsuya Maruhashi Kensuke Noma Yumiko Iwamoto Akimichi Iwamoto Nozomu Oda Masato Kajikawa Takeshi Matsumoto Takayuki Hidaka Yasuki Kihara Kazuaki Chayama Ayumu Nakashima Chikara Goto James K. Liao Yukihito Higashi 《PloS one》2014,9(10)
Objective
Rho-associated kinase (ROCK) signaling pathway has been shown to mediate various cellular functions including cell proliferation, migration, adhesion, apoptosis, and contraction, all of which may be involved in pathogenesis of atherosclerosis. Endogenous nitric oxide (NO) is well known to have an anti-atherosclerotic effect, whereas the exogenous NO-mediated cardiovascular effect still remains controversial. The purpose of this study was to evaluate the effect of exogenous NO on ROCK activity in vascular smooth muscle cells (VSMCs) in vitro and in vivo.Methods
VSMCs migration was evaluated using a modified Boyden chamber assay. ROCK activities were measured by Western blot analysis in murine and human VSMCs and aorta of mice treated with or without angiotensin II (Ang II) and/or sodium nitroprusside (SNP), an NO donor.Results
Co-treatment with SNP inhibited the Ang II-induced cell migration and increases in ROCK activity in murine and human VSMCs. Similarly, the increased ROCK activity 2 weeks after Ang II infusion in the mouse aorta was substantially inhibited by subcutaneous injection of SNP.Conclusions
These findings suggest that administration of exogenous NO can inhibit ROCK activity in VSMCs in vitro and in vivo. 相似文献6.
Yuichiro Kashima Masafumi Takahashi Yuji Shiba Naoki Itano Atsushi Izawa Jun Koyama Jun Nakayama Shun'ichiro Taniguchi Koji Kimata Uichi Ikeda 《PloS one》2013,8(3)
Background
Hyaluronan (HA) is a primary component of the extracellular matrix of cells, and it is involved in the pathogenesis of atherosclerosis. The purpose of this study was to investigate the role of HA in neointimal formation after vascular injury and determine its tissue-specific role in vascular smooth muscle cells (VSMCs) by using a cre-lox conditional transgenic (cTg) strategy.Methods and Results
HA was found to be expressed in neointimal lesions in humans with atherosclerosis and after wire-mediated vascular injury in mice. Inhibition of HA synthesis using 4-methylumbelliferone markedly inhibited neointimal formation after injury. In vitro experiments revealed that low-molecular-weight HA (LMW-HA) induced VSMC activation, including migration, proliferation, and production of inflammatory cytokines, and reactive oxygen species (ROS). The migration and proliferation of VSMCs were mediated by the CD44/RhoA and CD44/ERK1/2 pathways, respectively. Because HA synthase 2 (HAS2) is predominantly expressed in injured arteries, we generated cTg mice that overexpress the murine HAS2 gene specifically in VSMCs (cHAS2/CreSM22α mice) and showed that HA overexpression markedly enhanced neointimal formation after cuff-mediated vascular injury. Further, HA-overexpressing VSMCs isolated from cHAS2/CreSM22α mice showed augmented migration, proliferation, and production of inflammatory cytokines and ROS.Conclusion
VSMC-derived HA promotes neointimal formation after vascular injury, and HA may be a potential therapeutic target for cardiovascular disease. 相似文献7.
8.
Background
Leukocyte adhesion to the vascular endothelium and subsequent transendothelial migration play essential roles in the pathogenesis of cardiovascular diseases such as atherosclerosis. The leukocyte adhesion is mediated by localized activation of the endothelium through the action of inflammatory cytokines. The exact proinflammatory factors, however, that activate the endothelium and their cellular sources remain incompletely defined.Methods and Results
Using bone marrow-derived mast cells from wild-type, Tnf−/−, Ifng−/−, Il6−/− mice, we demonstrated that all three of these pro-inflammatory cytokines from mast cells induced the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), P-selectin, and E-selectin in murine heart endothelial cells (MHEC) at both mRNA and protein levels. Compared with TNF-α and IL6, IFN-γ appeared weaker in the induction of the mRNA levels, but at protein levels, both IL6 and IFN-γ were weaker inducers than TNF-α. Under physiological shear flow conditions, mast cell-derived TNF-α and IL6 were more potent than IFN-γ in activating MHEC and in promoting neutrophil adhesion. Similar observations were made when neutrophils or macrophages were used. Neutrophils and macrophages produced the same sets of pro-inflammatory cytokines as did mast cells to induce MHEC adhesion molecule expression, with the exception that macrophage-derived IFN-γ showed negligible effect in inducing VCAM-1 expression in MHEC.Conclusion
Mast cells, neutrophils, and macrophages release pro-inflammatory cytokines such as TNF-α, IFN-γ, and IL6 that induce expression of adhesion molecules in endothelium and recruit of leukocytes, which is essential to the pathogenesis of vascular inflammatory diseases. 相似文献9.
Elham Khanicheh Martina Mitterhuber Lifen Xu Stéphanie P. Haeuselmann Gabriela M. Kuster Beat A. Kaufmann 《PloS one》2013,8(3)
Background/Objectives
Inflammatory changes on the endothelium are responsible for leukocyte recruitment to plaques in atherosclerosis. Noninvasive assessment of treatment-effects on endothelial inflammation may be of use for managing medical therapy and developing novel therapies. We hypothesized that molecular imaging of vascular cell adhesion molecule-1 (VCAM-1) with contrast enhanced ultrasound (CEU) could assess treatment effects on endothelial phenotype in early atherosclerosis.Methods
Mice with atherosclerosis produced by gene deletion of the LDL-receptor and Apobec-1-editing protein were studied. At 12 weeks of age, mice received 8 weeks of regular chow or atorvastatin-enriched chow (10 mg/kg/day). At 20 weeks, CEU molecular imaging for aortic endothelial VCAM-1 expression was performed with VCAM-1-targeted (MBVCAM) and control microbubbles (MBCtr). Aortic wall thickness was assessed with high frequency ultrasound. Histology, immunohistology and Western blot were used to assess plaque burden and VCAM-1 expression.Results
Plaque burden was reduced on histology, and VCAM-1 was reduced on Western blot by atorvastatin, which corresponded to less endothelial expression of VCAM-1 on immunohistology. High frequency ultrasound did not detect differences in aortic wall thickness between groups. In contrast, CEU molecular imaging demonstrated selective signal enhancement for MBVCAM in non-treated animals (MBVCAM 2±0.3 vs MBCtr 0.7±0.2, p<0.01), but not in statin-treated animals (MBVCAM 0.8±0.2 vs MBCtr 1.0±0.2, p = ns; p<0.01 for the effect of statin on MBVCAM signal).Conclusions
Non-invasive CEU molecular imaging detects the effects of anti-inflammatory treatment on endothelial inflammation in early atherosclerosis. This easily accessible, low-cost technique may be useful in assessing treatment effects in preclinical research and in patients. 相似文献10.
Lingyun Zhu Guoxun Sun Hongjie Zhang Yan Zhang Xi Chen Xiaohong Jiang Xueyuan Jiang Stefan Krauss Junfeng Zhang Yang Xiang Chen-Yu Zhang 《PloS one》2009,4(1)
Background
Atherosclerosis is a complex pathological condition caused by a number of mechanisms including the accelerated proliferation of vascular smooth muscle cells (VSMCs). Diabetes is likely to be an important risk factor for atherosclerosis, as hyperglycemia induces vascular smooth muscle cell (VSMC) proliferation and migration and may thus contribute to the formation of atherosclerotic lesions. This study was performed to investigate whether PGC-1α, a PPARγ coactivator and metabolic master regulator, plays a role in regulating VSMC proliferation and migration induced by high glucose.Methodology/Principal Findings
PGC-1α mRNA levels are decreased in blood vessel media of STZ-treated diabetic rats. In cultured rat VSMCs, high glucose dose-dependently inhibits PGC-1α mRNA expression. Overexpression of PGC-1α either by infection with adenovirus, or by stimulation with palmitic acid, significantly reduces high glucose-induced VSMC proliferation and migration. In contrast, suppression of PGC-1α by siRNA mimics the effects of glucose on VSMCs. Finally, mechanistic studies suggest that PGC-1α-mediated inhibition of VSMC proliferation and migration is regulated through preventing ERK1/2 phosphorylation.Conclusions/Significance
These results indicate that PGC-1α is a key regulator of high glucose-induced proliferation and migration in VSMCs, and suggest that elevation of PGC-1α in VSMC could be a useful strategy in preventing the development of diabetic atherosclerosis. 相似文献11.
Caglayan E Romeo GR Kappert K Odenthal M Südkamp M Body SC Shernan SK Hackbusch D Vantler M Kazlauskas A Rosenkranz S 《PloS one》2010,5(10):e13608
Background
Profilin-1 is an ubiquitous actin binding protein. Under pathological conditions such as diabetes, profilin-1 levels are increased in the vascular endothelium. We recently demonstrated that profilin-1 overexpression triggers indicators of endothelial dysfunction downstream of LDL signaling, and that attenuated expression of profilin-1 confers protection from atherosclerosis in vivo.Methodology
Here we monitored profilin-1 expression in human atherosclerotic plaques by immunofluorescent staining. The effects of recombinant profilin-1 on atherogenic signaling pathways and cellular responses such as DNA synthesis (BrdU-incorporation) and chemotaxis (modified Boyden-chamber) were evaluated in cultured rat aortic and human coronary vascular smooth muscle cells (VSMCs). Furthermore, the correlation between profilin-1 serum levels and the degree of atherosclerosis was assessed in humans.Principal Findings
In coronary arteries from patients with coronary heart disease, we found markedly enhanced profilin expression in atherosclerotic plaques compared to the normal vessel wall. Stimulation of rat aortic and human coronary VSMCs with recombinant profilin-1 (10−6 M) in vitro led to activation of intracellular signaling cascades such as phosphorylation of Erk1/2, p70S6 kinase and PI3K/Akt within 10 minutes. Furthermore, profilin-1 concentration-dependently induced DNA-synthesis and migration of both rat and human VSMCs, respectively. Inhibition of PI3K (Wortmannin, ) or Src-family kinases (SU6656, PP2), but not PLCγ ( LY294002), completely abolished profilin-induced cell cycle progression, whereas PI3K inhibition partially reduced the chemotactic response. Finally, we found that profilin-1 serum levels were significantly elevated in patients with severe atherosclerosis in humans (p<0.001 vs. no atherosclerosis or control group). U73122Conclusions
Profilin-1 expression is significantly enhanced in human atherosclerotic plaques compared to the normal vessel wall, and the serum levels of profilin-1 correlate with the degree of atherosclerosis in humans. The atherogenic effects exerted by profilin-1 on VSMCs suggest an auto-/paracrine role within the plaque. These data indicate that profilin-1 might critically contribute to atherogenesis and may represent a novel therapeutic target. 相似文献12.
Noriyuki Komura Norikazu Maeda Takuya Mori Shinji Kihara Hideaki Nakatsuji Ayumu Hirata Yoshihiro Tochino Tohru Funahashi Iichiro Shimomura 《PloS one》2013,8(8)
Aims
Inflammation is closely associated with the development of atherosclerosis and metabolic syndrome. Adiponectin, an adipose-derived secretory protein, possesses an anti-atherosclerotic property. The present study was undertaken to elucidate the presence and significance of adiponectin in vasculature.Methods and Results
Immunofluorescence staining was performed in aorta of wild-type (WT) mice and demonstrated that adiponectin was co-stained with CD31. Thoracic aorta was cut through and then aortic intima was carefully shaved from aorta. Western blotting showed the existence of adiponectin protein in aortic intima, while there was no adiponectin mRNA expression. Adiponectin knockout (Adipo-KO) and WT mice were administered with a low-dose and short-term lipopolysaccharide (LPS) (1 mg/kg of LPS for 4 hours). The endothelium vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were highly increased in Adipo-KO mice compared to WT mice after LPS administration.Conclusions
Adiponectin protein exists in aortic endothelium under steady state and may protect vasculature from the initiation of atherosclerosis. 相似文献13.
Jong Kui Jun Wang Lok Lee Hee Geun Park Sang Ki Lee Sun Hyo Jeong Young Ran Lee 《Journal of Exercise Nutrition & Biochemistry》2014,18(1):119-127
[Purpose]
The purpose of this study was to investigate the effects of the different endurance exercise intensities on the macrophage infiltration and adipocyte inflammation of ovariectomized rats.[Methods]
24 female SD rats (6 weeks old) were randomly assigned to sham control (SC; n=6), ovariectomized control (OC; n=6), ovariectomized low intensity exercise (OL; n=6), and ovariectomized moderate intensity exercise (OM; n=6) groups. The two training groups ran for 60 min/day, 5 times/ week at 18 and 26m/min for 16 weeks. Twenty-four hours after the last exercise session, rats were sacrified, and epididymal pads were analyzed. F4/80 and IL-6 expressions were evaluated by western blotting. ICAM-1, VCAM-1 TLR4, TNF-α, and MCP-1 mRNA expressions were evaluated by RT-PCR.[Results]
In comparison with OC group, OM group showed significantly lower body weight gain and adipose tissue mass. Also, OM group markedly inhibited F4/80 expression, adhesion molecule (ICAM-1, VCAM-1) and pro-inflammatory cytokines (TLR4, TNF-α, MCP-1) mRNA expressions in adipose tissue. In contrast, OL group partially prevented body weight gain while other examined parameter were unaffected by low intensity exercise training.[Conclusion]
The results of this study suggest that OM group inhibits visceral macrophage infiltration by suppressing the adhesion molecules. It may also attenuate cytokine production in the adipose tissue by repressing the TLR4-mediated pro-inflammatory signaling cascades in ovariectomized rats. 相似文献14.
H.J. Liu X.L. Wang L. Zhang Y. Qiu T.J. Li R. Li M.C. Wu L.X. Wei Y.C. Rui 《Phytomedicine》2009,16(2-3):138-145
It has been reported that oxidatively modified low-density lipoprotein (Ox-LDL) involvement with vascular endothelial growth factor (VEGF) and foam cell formation play an important role in atherosclerosis (AS). Protective effects of Ginkgo biloba extract (EGb 761) have been identified for some cardiovascular and neurological disorders. The aim of this study was to investigate whether Ox-LDL regulates VEGF expression in human THP-1 monocytes, as well as the effect of EGb 761 on VEGF expression and the formation of foam cells. After exposure to Ox-LDL alone or in combination with EGb 761 for up to 48 h, cell viability was measured using the MTT assay. VEGF protein content in the supernatant was analyzed by enzyme-linked immunosorbent assay (ELISA). VEGF mRNA was determined by real-time PCR. To determine the effect of EGb 761 on foam cell formation, an Ox-LDL-induced foam cell model was used. Ox-LDL inhibited the growth of THP-1 cells and EGb 761 increased the cell survival rate. Ox-LDL markedly increased VEGF expression in THP-1 cells in a time- and concentration-dependent manner, which was significantly suppressed by EGb 761. EGb 761 also inhibited monocyte/macrophage-derived foam cell formation. These results suggest that Ox-LDL is involved in the development of human AS through VEGF induction in monocytes, and that EGb 761 prevents in vitro atherogenesis, probably via downregulation of VEGF expression in monocytes and inhibition of monocyte/macrophage-derived foam cell formation. The findings suggest a mechanism for the in vivo anti-AS effect of EGb 761 and support its potential clinical use in AS. 相似文献
15.
Background
We recently demonstrated that tyrosine sulfation is an important contributor to monocyte recruitment and retention in a mouse model of atherosclerosis. P-selectin glycoprotein ligand-1 (Psgl-1) is tyrosine-sulfated in mouse monocyte/macrophages and its interaction with P-selectin is important in monocyte recruitment in atherosclerosis. However, whether tyrosine sulfation is required for the P-selectin binding function of mouse Psgl-1 is unknown. Here we test the function of native Psgl-1 expressed in leukocytes lacking endogenous tyrosylprotein sulfotransferase (TPST) activity.Methodology/Principal Findings
Psgl-1 function was assessed by examining P-selectin dependent leukocyte rolling in post-capillary venules of C57BL6 mice transplanted with hematopoietic progenitors from wild type (WT→B6) or Tpst1;Tpst2 double knockout mice (Tpst DKO→B6) which lack TPST activity. We observed that rolling flux fractions were lower and leukocyte rolling velocities were higher in Tpst DKO→B6 venules compared to WT→B6 venules. Similar results were observed on immobilized P-selectin in vitro. Finally, Tpst DKO leukocytes bound less P-selectin than wild type leukocytes despite equivalent surface expression of Psgl-1.Conclusions/Significance
These findings provide direct and convincing evidence that tyrosine sulfation is required for optimal function of mouse Psgl-1 in vivo and suggests that tyrosine sulfation of Psgl-1 contributes to the development of atherosclerosis. 相似文献16.
Michelle M. Averill Eung Ju Kim Leela Goodspeed Shari Wang Savitha Subramanian Laura J. Den Hartigh Chongren Tang Yilei Ding Catherine A. Reardon Godfrey S. Getz Alan Chait 《PloS one》2014,9(10)
Objective
High density lipoprotein (HDL) cholesterol levels are inversely related to cardiovascular disease risk and associated with a reduced risk of type 2 diabetes. Apolipoprotein A-I (apoA-I; major HDL protein) mimetics have been reported to reduce atherosclerosis and decrease adiposity. This study investigated the effect of L4F mimetic peptide and apoA-I overexpression on weight gain, insulin resistance, and atherosclerosis in an LDL receptor deficient (Ldlr-/-) model fed a high fat high sucrose with cholesterol (HFHSC) diet.Methods
Studies in differentiated 3T3-L1 adipocytes tested whether L4F could inhibit palmitate-induced adipocyte inflammation. In vivo studies used male Ldlr-/- mice fed a HFHSC diet for 12 weeks and were injected daily with L4F (100 µg/mouse) subcutaneously during the last 8 weeks. Wild-type and apoA-I overexpressing Ldlr-/- mice were fed HFHSC diet for 16 weeks.Results
Neither L4F administration nor apoA-I overexpression affected weight gain, total plasma cholesterol or triglycerides in our studies. While pre-treatment of 3T3-L1 adipocytes with either L4F or HDL abolished palmitate-induced cytokine expression in vitro, L4F treatment did not affect circulating or adipose tissue inflammatory markers in vivo. Neither L4F administration nor apoA-I overexpression affected glucose tolerance. ApoA-I overexpression significantly reduced atherosclerotic lesion size, yet L4F treatment did not affect atherosclerosis.Conclusion
Our results suggest that neither L4F (100 µg/day/mouse) nor apoA-I overexpression affects adiposity or insulin resistance in this model. We also were unable to confirm a reduction in atherosclerosis with L4F in our particular model. Further studies on the effect of apoA-I mimetics on atherosclerosis and insulin resistance in a variety of dietary contexts are warranted. 相似文献17.
Kim Heang Ly Alexis Régent Elsa Molina Sofiane Saada Philippe Sindou Claire Le-Jeunne Antoine Brézin Véronique Witko-Sarsat Fran?ois Labrousse Pierre-Yves Robert Philippe Bertin Jean-Louis Bourges Anne-Laure Fauchais Elisabeth Vidal Luc Mouthon Marie-Odile Jauberteau 《Arthritis research & therapy》2014,16(6)
Introduction
Giant cell arteritis (GCA) is characterized by intimal hyperplasia leading to ischaemic manifestations that involve large vessels. Neurotrophins (NTs) and their receptors (NTRs) are protein factors for growth, differentiation and survival of neurons. They are also involved in the migration of vascular smooth muscle cells (VSMCs). Our aim was to investigate whether NTs and NTRs are involved in vascular remodelling of GCA.Methods
We included consecutive patients who underwent a temporal artery biopsy for suspected GCA. We developed an enzymatic digestion method to obtain VSMCs from smooth muscle cells in GCA patients and controls. Neurotrophin protein and gene expression and functional assays were studied from these VSMCs. Neurotrophin expression was also analysed by immunohistochemistry in GCA patients and controls.Results
Whereas temporal arteries of both GCA patients (n = 22) and controls (n = 21) expressed nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) and sortilin, immunostaining was more intense in GCA patients, especially in the media and intima, while neurotrophin-3 (NT-3) and P75 receptor (P75NTR) were only detected in TA from GCA patients. Expression of TrkB, a BDNF receptor, was higher in GCA patients with ischaemic complications. Serum NGF was significantly higher in GCA patients (n = 28) vs. controls (n = 48), whereas no significant difference was found for BDNF and NT-3. NGF and BDNF enhanced GCA-derived temporal artery VSMC proliferation and BDNF facilitated migration of temporal artery VSMCs in patients with GCA compared to controls.Conclusions
Our results suggest that NTs and NTRs are involved in vascular remodelling of GCA. In GCA-derived temporal artery VSMC, NGF promoted proliferation and BDNF enhanced migration by binding to TrkB and p75NTR receptors. Further experiments are needed on a larger number of VSMC samples to confirm these results.Electronic supplementary material
The online version of this article (doi:10.1186/s13075-014-0487-z) contains supplementary material, which is available to authorized users. 相似文献18.
Anne Mette Fisker Hag Sune Folke Pedersen Christina Christoffersen Tina Binderup Mette Munk Jensen Jesper Tranekj?r J?rgensen Dorthe Skovgaard Rasmus Sejersten Ripa Andreas Kjaer 《PloS one》2012,7(11)
Aim
To study whether 18F-FDG can be used for in vivo imaging of atherogenesis by examining the correlation between 18F-FDG uptake and gene expression of key molecular markers of atherosclerosis in apoE−/− mice.Methods
Nine groups of apoE−/− mice were given normal chow or high-fat diet. At different time-points, 18F-FDG PET/contrast-enhanced CT scans were performed on dedicated animal scanners. After scans, animals were euthanized, aortas removed, gamma counted, RNA extracted from the tissue, and gene expression of chemo (C-X-C motif) ligand 1 (CXCL-1), monocyte chemoattractant protein (MCP)-1, vascular cell adhesion molecule (VCAM)-1, cluster of differentiation molecule (CD)-68, osteopontin (OPN), lectin-like oxidized LDL-receptor (LOX)-1, hypoxia-inducible factor (HIF)-1α, HIF-2α, vascular endothelial growth factor A (VEGF), and tissue factor (TF) was measured by means of qPCR.Results
The uptake of 18F-FDG increased over time in the groups of mice receiving high-fat diet measured by PET and ex vivo gamma counting. The gene expression of all examined markers of atherosclerosis correlated significantly with 18F-FDG uptake. The strongest correlation was seen with TF and CD68 (p<0.001). A multivariate analysis showed CD68, OPN, TF, and VCAM-1 to be the most important contributors to the uptake of 18F-FDG. Together they could explain 60% of the 18F-FDG uptake.Conclusion
We have demonstrated that 18F-FDG can be used to follow the progression of atherosclerosis in apoE−/− mice. The gene expression of ten molecular markers representing different molecular processes important for atherosclerosis was shown to correlate with the uptake of 18F-FDG. Especially, the gene expressions of CD68, OPN, TF, and VCAM-1 were strong predictors for the uptake. 相似文献19.
Javier Conde Morena Scotece Verónica López Rodolfo Gómez Francisca Lago Jesús Pino Juan Jesús Gómez-Reino Oreste Gualillo 《PloS one》2012,7(12)
Background
Osteoarthritis (OA) and rheumatoid arthritis (RA), the most common rheumatic diseases, are characterized by irreversible degeneration of the joint tissues. There are several factors involved in the pathogenesis of these diseases including pro-inflammatory cytokines, adipokines and adhesion molecules.Objective
Up to now, the relationship between adipokines and adhesion molecules at cartilage level was not explored. Thus, the aim of this article was to study the effect of leptin and adiponectin on the expression of VCAM-1 in human and murine chondrocytes. For completeness, intracellular signal transduction pathway was also explored.Methods
VCAM-1 expression was assessed by quantitative RT-PCR and western blot analysis upon treatment with leptin, adiponectin and other pertinent reagents in cultured human primary chondrocytes. Signal transduction pathways have been explored by using specific pharmacological inhibitors in the adipokine-stimulated human primary chondrocytes and ATDC5 murine chondrocyte cell line.Results
Herein, we demonstrate, for the first time, that leptin and adiponectin increase VCAM-1 expression in human and murine chondrocytes. In addition, both adipokines have additive effect with IL-1β. Finally, we demonstrate that several kinases, including JAK2, PI3K and AMPK are at a play in the intracellular signalling of VCAM-1 induction.Conclusions
Taken together, our results suggest that leptin and adiponectin could perpetuate cartilage-degrading processes by inducing also factors responsible of leukocyte and monocyte infiltration at inflamed joints. 相似文献20.
Ashraf Yusuf Rangrez Eléonore M'Baya-Moutoula Valérie Metzinger-Le Meuth Lucie Hénaut Mohamed Seif el Islam Djelouat Joyce Benchitrit Ziad A. Massy Laurent Metzinger 《PloS one》2012,7(10)