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1.
Angiogenesis and chemokines in rheumatoid arthritis and other systemic inflammatory rheumatic diseases 总被引:9,自引:3,他引:6
Bodolay E Koch AE Kim J Szegedi G Szekanecz Z 《Journal of cellular and molecular medicine》2002,6(3):357-376
Angiogenesis, the formation of new vessels, is important in the pathogenesis of rheumatoid arthritis (RA) and other inflammatory diseases. Chemotactic cytokines termed chemokines mediate the ingress of leukocytes, including neutrophils and monocytes into the inflamed synovium. In this review, authors discuss the role of the most important angiogenic factors and angiogenesis inhibitors, as well as relevant chemokines and chemokine receptors involved in chronic inflammatory rheumatic diseases. RA was chosen as a prototype to discuss these issues, as the majority of studies on the role of angiogenesis and chemokines in inflammatory diseases were carried out in arthritis. However, other systemic inflammatory (autoimmune) diseases including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren's syndrome (SS), mixed connective tissue disease (MCTD), polymyositis/dermatomyositis (PM/DM) and systemic vasculites are also discussed in this context. As a number of chemokines may also play a role in neovascularizaton, this issue is also described here. Apart from discussing the pathogenic role of angiogenesis and chemokines, authors also review the regulation of angiogenesis and chemokine production by other inflammatory meditors, as well as the important relevance of neovascularization and chemokines for antirheumatic intervention. 相似文献
2.
阻塞性睡眠呼吸暂停综合征(Obstructive sleep apnea,OSA)是一种发病率高,具有一定潜在危险的全身性疾病,同时也是心脑血管疾病的一个独立危险因素。其主要病理生理改变是睡眠过程中反复发生低氧和再氧合而引起的氧化应激反应,引发炎症反应而导致心、脑血管为主的多系统损害。流行病学研究证据表明,一些循环水平的炎症因子在OSA患者中升高,与心脑血管疾病发病风险相关。包括细胞粘附分子如粘附分子-1(intercellular adhesion molecule-1,ICAM-1)和选择素(selectins),细胞因子如肿瘤坏死因子α(TNF-a)和白细胞介素-6(interleukin-6,IL-6),趋化因子如白细胞介素-8(interleukin 8,IL-8)和C-反应蛋白(C-reactive protein)。此外,动脉粥样硬化是OSA导致心脑血管疾病的重要的机制,OSA后的炎症反应在动脉粥样硬化形成及发展的过程中起着至关重要的作用,本文重点对OSA后炎症因子启动及血管内皮调节的新近研究进行综述。 相似文献
3.
Cardiovascular morbidity and mortality are becoming major health concerns for adults with inflammatory rheumatic diseases. The enhanced atherogenesis in this patient population is promoted by the exposure to traditional risk factors as well as nontraditional cardiovascular insults, such as corticosteroid therapy, chronic inflammation and autoantibodies. Despite definite differences between many adult-onset and pediatric-onset rheumatologic diseases, it is extremely likely that atherosclerosis will become the leading cause of morbidity and mortality in this pediatric patient population. Because cardiovascular events are rare at this young age, surrogate measures of atherosclerosis must be used. The three major noninvasive vascular measures of early atherosclerosis - namely, flow-mediated dilatation, carotid intima-media thickness and pulse wave velocity - can be performed easily on children. Few studies have explored the prevalence of cardiovascular risk factors and even fewer have used the surrogate vascular measures to document signs of early atherosclerosis in children with pediatric-onset rheumatic diseases. The objective of this review is to provide an overview on cardiovascular risk and early atherosclerosis in pediatric-onset systemic lupus erythematosus, juvenile idiopathic arthritis and juvenile dermatomyositis patients, and to review cardiovascular preventive strategies that should be considered in this population. 相似文献
4.
Angiogenesis is important in the pathogenesis of systemic inflammatory rheumatic diseases, a family of related disorders that includes rheumatoid arthritis and systemic sclerosis. Rheumatoid arthritis is the rheumatic disease in which the role of angiogenesis has been studied most extensively. However, whereas rheumatoid arthritis is characterized by excessive angiogenesis, the situation is not as clear cut in other rheumatic diseases. For example, systemic sclerosis is characterized by reduced capillary density with insufficient angiogenic responses. Results with angiogenesis inhibitors are controversial, and there is--in parallel--a wide range of upregulated angiogenic factors such as vascular endothelial growth factor. Dysregulation of angiogenesis in systemic sclerosis is accompanied by other pathogenic processes, including fibrosis, autoimmunity and vasculopathy. Animal models with at least partial features of the vasculopathy observed in systemic sclerosis include wound healing models, graft versus host disease models and, in particular, the University of California at Davis line 200 chicken model of systemic sclerosis. 相似文献
5.
Middleton J Americh L Gayon R Julien D Aguilar L Amalric F Girard JP 《Arthritis research & therapy》2004,6(2):60-72
Endothelial cells are active participants in chronic inflammatory diseases. These cells undergo phenotypic changes that can
be characterised as activated, angiogenic, apoptotic and leaky. In the present review, these phenotypes are described in the
context of human rheumatoid arthritis as the disease example. Endothelial cells become activated in rheumatoid arthritis pathophysiology,
expressing adhesion molecules and presenting chemokines, leading to leukocyte migration from the blood into the tissue. Endothelial
cell permeability increases, leading to oedema formation and swelling of the joints. These cells proliferate as part of the
angiogenic response and there is also a net increase in the turnover of endothelial cells since the number of apoptotic endothelial
cells increases. The endothelium expresses various cytokines, cytokine receptors and proteases that are involved in angiogenesis,
proliferation and tissue degradation. Associated with these mechanisms is a change in the spectrum of genes expressed, some
of which are relatively endothelial specific and others are widely expressed by other cells in the synovium. Better knowledge
of molecular and functional changes occurring in endothelial cells during chronic inflammation may lead to the development
of endothelium-targeted therapies for rheumatoid arthritis and other chronic inflammatory diseases. 相似文献
6.
Systemic vasculitis, an inflammatory necrotizing disease of the blood vessel walls, can occur secondary to autoimmune diseases, including connective tissue diseases. Various pathogenic mechanisms have been implicated in the induction of vasculitis, including cell-mediated inflammation, immune complex-mediated inflammation and autoantibody-mediated inflammation. This inflammatory activity is believed to contribute to accelerated atherosclerosis, and also leads to increased risk for cardiovascular events in patients with rheumatoid arthritis and systemic lupus erythematosus. Endothelial cell activation is a common pathogenic pathway in the systemic vasculitis associated with rheumatoid arthritis and systemic lupus erythematosus, with elevated levels of endothelin-1 potentially inducing vascular dysregulation. 相似文献
7.
The increased burden of cardiovascular disease in patients with rheumatoid arthritis and systemic lupus erythematosus has
recently become the focus of intense investigation. Proatherogenic risk factors and dysregulated inflammation are the main
culprits, leading to enhanced atherosclerosis in subgroups of patients with inflammatory diseases. Common molecular pathways
shared by atherosclerosis and inflammatory disease may be involved. In this review we map the key determinants of the increased
incidence of cardiovascular disease in patients with inflammatory diseases at each step of the atherogenesis. 相似文献
8.
R. Campos-Rodríguez R.A. Jarillo-Luna M. Godínez-Victoria E. Mera-Jiménez A.A. Reséndiz-Albor 《Bioscience Hypotheses》2009,2(5):331-338
Estrogens and glucocorticoids have synergistic effects in the micro and macrovasculature of endothelial cells. Whereas in the former they both have pro-inflammatory effects, in the latter they both inhibit the expression of adhesion molecules. Since the molecular basis of this synergy has not been defined, we propose possible mechanisms of interaction. An understanding of the functional interaction between estrogens and glucocorticoids in the endothelial cells of the micro and macrovasculature may contribute to clarifying the role of the endothelial cells of different vascular beds during the inflammatory response and in chronic inflammation. These advances could contribute to the design of more effective therapeutic strategies for the prevention of diseases, such as atherosclerosis, systemic lupus erythematosus and rheumatoid arthritis, in which the inflammatory process plays an important pathogenic role. 相似文献
9.
Uncontrolled or sustained inflammation is the underlying cause of or actively contributes to the progression of many chronic pathologies such as atherosclerosis, arthritis, or neuroinflammatory diseases. Matricellular proteins of the CCN family (CYR61/CTGF/NOV) have emerged as localized multitasking signal integrators. These structurally conserved secreted proteins specifically interact with and signal through various extracellular partners, in particular integrins, which enable them to play crucial roles in various processes including development, angiogenesis, wound healing and diseases such as fibrosis, vascular disease and cancer. In this review, we discuss the possibility that the CCN family members could represent a putative new class of modulators of inflammation. In this context, we focused on their relationship with cytokines and chemokines. In vitro, CCN expression is finely regulated by diverse inflammatory mediators including cytokines (TNFα, IL1β, TGF-β), small factors such as prostaglandins, nitric oxide, histamine and serotonin, and extracellular matrix enzymes. In addition, CCN proteins acting alone or in concert with their specific partners appear to be potent regulators of the production of cytokines and chemokines in a context-dependent manner. Finally, emerging studies suggest a potential role for CCN proteins in chronic inflammatory diseases such as atherosclerosis, rheumatoid arthritis, inflammatory kidney diseases and neuroinflammatory pathologies such as Alzheimer’s disease. CCN members could therefore represent new potential therapeutic targets for drug development against such diseases. 相似文献
10.
Frostegård J 《Arthritis research & therapy》2011,13(3):225
During recent years atherosclerosis, the major cause of cardiovascular disease (CVD), has been recognised as a chronic inflammatory
condition in which rupture of atherosclerotic lesions appears to play a major role. The risk of CVD is raised in many rheumatic
diseases. This risk is high in systemic lupus erythematosus - as much as a 50-times increase among middle-aged women has been
reported. Studies on CVD and atherosclerosis in rheumatic disease could thus provide interesting information about CVD and
atherosclerosis in addition to being an important clinical problem. A combination of traditional and nontraditional risk factors
accounts for the increased risk of CVD and atherosclerosis in rheumatic disease. One interesting possibility is that atherosclerotic
lesions in rheumatic disease are more prone to rupture than normal atherosclerotic lesions. It is also likely that increased
risk of thrombosis may play an important role, not least in systemic lupus erythematosus. Further, it is not clear whether
an increased risk of CVD is a general feature of rheumatic disease, or whether this only occurs among subgroups of patients.
It should be emphasised that there is an apparent lack of treatment studies where CVD in rheumatic disease is the end point.
Control of disease activity and of traditional risk factors, however, appears to be well founded in relation to CVD in rheumatic
disease. Further studies are needed to determine the exact role of lipid-lowering drugs as statins. Hopefully novel therapies
can be developed that target the causes of the inflammation in atherosclerotic lesions both in rheumatic patients and in the
general population. 相似文献
11.
Chidlow JH Shukla D Grisham MB Kevil CG 《American journal of physiology. Gastrointestinal and liver physiology》2007,293(1):G5-G18
Angiogenesis is now understood to play a major role in the pathology of chronic inflammatory diseases and is indicated to exacerbate disease pathology. Recent evidence shows that angiogenesis is crucial during inflammatory bowel disease (IBD) and in experimental models of colitis. Examination of the relationship between angiogenesis and inflammation in experimental colitis shows that initiating factors for these responses simultaneously increase as disease progresses and correlate in magnitude. Recent studies show that inhibition of the inflammatory response attenuates angiogenesis to a similar degree and, importantly, that inhibition of angiogenesis does the same to inflammation. Recent data provide evidence that differential regulation of the angiogenic mediators involved in IBD-associated chronic inflammation is the root of this pathological angiogenesis. Many factors are involved in this phenomenon, including growth factors/cytokines, chemokines, adhesion molecules, integrins, matrix-associated molecules, and signaling targets. These factors are produced by various vascular, inflammatory, and immune cell types that are involved in IBD pathology. Moreover, recent studies provide evidence that antiangiogenic therapy is a novel and effective approach for IBD treatment. Here we review the role of pathological angiogenesis during IBD and experimental colitis and discuss the therapeutic avenues this recent knowledge has revealed. 相似文献
12.
Increasing evidences have suggested vascular endothelial inflammatory processes are the initiator of atherosclerosis. Bestrophin 3 (Best-3) is involved in the regulation of cell proliferation, apoptosis and differentiation of a variety of physiological functions, but its function in cardiovascular system remains unclear. In this study, we investigated the effect of Best-3 on endothelial inflammation. We first demonstrated that Best-3 is expressed in endothelial cells and decreased after tumor necrosis factor-α (TNFα) challenge. Overexpression of Best-3 significantly attenuated TNFα-induced expression of adhesion molecules and chemokines, and subsequently inhibited the adhesion of monocytes to human umbilical vein endothelial cells (HUVECs). Conversely, knockdown of Best-3 with siRNA resulted in an enhancement on TNFα-induced expression of adhesion molecules and chemokines and adhesion of monocytes to HUVECs. Furthermore, overexpression of Best-3 with adenovirus dramatically ameliorated inflammatory response in TNFα-injected mice. Mechanistically, we found up-regulation of Best-3 inhibited TNFα-induced IKKβ and IκBα phosphorylation, IκBα degradation and NF-κB translocation. Our results demonstrated that Best-3 is an endogenous inhibitor of NF-κB signaling pathway in endothelial cells, suggesting that forced Best-3 expression may be a novel approach for the treatment of vascular inflammatory diseases. 相似文献
13.
Nicole Reich Christian Beyer Kolja Gelse Alfiya Akhmetshina Clara Dees Jochen Zwerina Georg Schett Oliver Distler Jörg H.W. Distler 《Journal of cellular and molecular medicine》2011,15(4):756-762
Microparticles (MPs) are small membrane‐vesicles that accumulate in the synovial fluids of patients with rheumatoid arthritis (RA). In the arthritic joints, MPs induce a pro‐inflammatory and invasive phenotype in synovial fibroblasts (SFs). The present study investigated whether activation of SFs by MPs stimulates angiogenesis in the inflamed joints of patients with RA. MPs were isolated from Jurkat cells and U937 cells by differential centrifugation. SFs were co‐cultured with increasing numbers of MPs. The effects of supernatants from co‐cultures on endothelial cells were studied in vitro and in vivo using MTT assays, annexin V and propidium iodide staining, trans‐well migration assays and modified matrigel pouch assays. MPs strongly induced the expression of the pro‐angiogenic ELR+ chemokines CXCL1, CXCL2, CXCL3, CXCL5 and CXCL6 in RASFs. Other vascular growth factors were not induced. Supernatants from co‐cultures enhanced the migration of endothelial cells, which could be blocked by neutralizing antibodies against ELR+ chemokines. Consistent with the specific induction of ELR+ chemokines, proliferation and viability of endothelial cells were not affected by the supernatants. In the in vivo bio‐chamber assay, supernatants from RASFs co‐cultured with MPs stimulated angiogenesis with a significant increase of vessels infiltrating into the matrigel chamber. We demonstrated that MPs activate RASFs to release pro‐angiogenic ELR+ chemokines. These pro‐angiogenic mediators enhance migration of endothelial cells and stimulate the formation of new vessels. Our data suggest that MPs may contribute to the hypervascularization of inflamed joints in patients with rheumatoid arthritis. 相似文献
14.
Oxidized low-density lipoprotein (OxLDL) is a risk factor for atherosclerosis, due to its role in endothelial dysfunction and foam cell formation. Tissue-resident cells such as macrophages and mast cells release inflammatory mediators upon activation that in turn cause endothelial activation and monocyte adhesion. Two of these mediators are tumor necrosis factor (TNF)-α, produced by macrophages, and histamine, produced by mast cells. Static and microfluidic flow experiments were conducted to determine the number of adherent monocytes on vascular endothelium activated by supernatants of oxLDL-treated macrophages and mast cells or directly by oxLDL. The expression of adhesion molecules on activated endothelial cells and the concentration of TNF-α and histamine in the supernatants were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. A low dose of oxLDL (8 μg/ml), below the threshold for the clinical presentation of coronary artery disease, was sufficient to activate both macrophages and mast cells and synergistically increase monocyte-endothelium adhesion via released TNF-α and histamine. The direct exposure of endothelial cells to a much higher dose of oxLDL (80 μg/ml) had less effect on monocyte adhesion than the indirect activation via oxLDL-treated macrophages and mast cells. The results of this work indicate that the co-activation of macrophages and mast cells by oxLDL is an important mechanism for the endothelial dysfunction and atherogenesis. The observed synergistic effect suggests that both macrophages and mast cells play a significant role in early stages of atherosclerosis. Allergic patients with a lipid-rich diet may be at high risk for cardiovascular events due to high concentration of low-density lipoprotein and histamine in arterial vessel walls. 相似文献
15.
Tanaka Y 《Histology and histopathology》2000,15(4):1169-1176
The adhesive function of integrins is regulated through cytoplasmic signaling induced by several stimuli, whose process is designated "inside-out signaling". A large number of leukocytes are rapidly recruited to the sites of inflammation where they form an essential component of the response to infection, injury, autoimmune disorders, allergy, tumor invasion, atherosclerosis and so on. The recruitment of leukocytes into tissue is regulated by a sequence of interactions between the circulating leukocytes and the endothelial cells. Leukocyte integrins play a pivotal role in leukocyte adhesion to endothelial cells. During the process, the activation of integrins by various chemoattractants, especially chemokines, is essential for integrin-mediated adhesion in which a signal transduced to the leukocyte converts the functionally inactive integrin to an active adhesive configuration. We have proposed that H-Ras-sensitive activation of phosphoinositide 3 (PI 3)-kinase and subsequent profilin-mediated actin polymerization, can be involved in chemokine-induced integrin-dependent adhesion of T cells. The present review documents the relevance of cytoplasmic signaling and cytoskeletal assembly to integrin-mediated adhesion induced by chemoattractants including chemokines during inflammatory processes. In contrast, various adhesion molecules are known to transduce extracellular information into cytoplasm, which leads to T cell activation and cytokine production from the cells, designated "outside-in signaling". Such a bi-directional "cross-talking" among adhesion molecules and cytokines is most relevant to inflammatory processes by augmenting immune cell migration from circulation into inflamed tissue such as rheumatoid arthritis, tumor invasion, Beh?et's disease and atherosclerosis. 相似文献
16.
Monocyte chemoattractant protein-1--a major contributor to the inflammatory process associated with diabetes 总被引:2,自引:0,他引:2
There is evidence that strongly suggests that inflammation plays an important role in diabetes and cardiovascular diseases. The high glucose-induced inflammatory process is characterised by the cooperation of a complex network of inflammatory molecules such as cytokines, adhesion molecules, growth factors, and chemokines. Among the chemokine family, monocyte chemoattractant protein (MCP-1) is a potent chemotactic factor, which is upregulated at sites of inflammation being in control of leukocytes trafficking. Here, we review the current knowledge on MCP-1 and its regulation by high glucose level in vascular cells involved in diabetes-induced accelerated atherosclerosis. The signalling pathways involved in MCP-1 modulation by high glucose, the proximal signalling events that stimulate downstream effects and the role of this chemokine in the pathophysiology of diabetes and its complications, are discussed. 相似文献
17.
Dennis D. Taub 《Cytokine & growth factor reviews》1996,7(4):355-376
Leukocyte recruitment from the circulation into inflammatory tissues requires a series of soluble and cell-bound signals between the responding leukocyte and vascular endothelial barrier. Chemotactic factors are believed to be responsible for this selective adhesion and transmigration. A superfamily of small, soluble, structurally-related molecules called ‘chemokines’ have been identified and shown to selectively promote the rapid adhesion and chemotaxis of a variety of leukocyte subtypes both in vivo and in vitro. Chemokines are produced by almost every cell type in the body in response to a number of inflammatory signals, in particular those which activate leukocyteendothelial cell interactions. These molecules also appear to play important roles in hematopoesis, cellular activation, and leukocyte effector functions. In addition, chemokines have been found in the tissues of a variety of disease states characterized by distinct leukocytic infiltrates, including rheumatoid arthritis, sepsis, atherosclerosis, asthma, psoriasis, ischemia/reperfusion injury, HIV replication, and a variety of pulmonary disease states. This review will primarily focus on the role of chemokines in cell adhesion and trafficking as well as their role as effector molecules. 相似文献
18.
Xiumei Chen Jianzhong Lin Tingting Hu Zhiyun Ren Linnan Li Irbaz Hameed Xiaoyu Zhang Chen Men Yan Guo Di Xu Yiyang Zhan 《Journal of cellular physiology》2019,234(7):10990-11000
Oxidized low-density lipoprotein (Ox-LDL)-induced endothelial cell injury plays a crucial role in the pathogenesis of atherosclerosis (AS). Plasma galectin-3 (Gal-3) is elevated inside and drives diverse systemic inflammatory disorders, including cardiovascular diseases. However, the exact role of Gal-3 in ox-LDL-mediated endothelial injury remains unclear. This study explores the effects of Gal-3 on ox-LDL-induced endothelial dysfunction and the underlying molecular mechanisms. In this study, Gal-3, integrin β1, and GTP-RhoA in the blood and plaques of AS patients were examined by ELISA and western blot respectively. Their levels were found to be obviously upregulated compared with non-AS control group. CCK8 assay and flow cytometry analysis showed that Gal-3 significantly decreased cell viability and promoted apoptosis in ox-LDL-treated human umbilical vascular endothelial cells (HUVECs). The upregulation of integrinβ1, GTP-RhoA, p-JNK, p-p65, p-IKKα, and p-IKKβ induced by ox-LDL was further enhanced by treatment with Gal-3. Pretreatment with Gal-3 increased expression of inflammatory factors (interleukin [IL]-6, IL-8, and IL-1β), chemokines(CXCL-1 and CCL-2) and adhesion molecules (VCAM-1 and ICAM-1). Furthermore, the promotional effects of Gal-3 on NF-κB activation and inflammatory factors in ox-LDL-treated HUVECs were reversed by the treatments with integrinβ1-siRNA or the JNK inhibitor. We also found that integrinβ1-siRNA decreased the protein expression of GTP-RhoA and p-JNK, while RhoA inhibitor partially reduced the upregulated expression of p-JNK induced by Gal-3. In conclusion, our finding suggests that Gal-3 exacerbates ox-LDL-mediated endothelial injury by inducing inflammation via integrin β1-RhoA-JNK signaling activation. 相似文献
19.
《Cell Adhesion & Migration》2013,7(2):67-75
Leukocyte transendothelial migration (TEM) is one of the crucial steps during inflammation. A better understanding of the key molecules that regulate leukocyte extravasation aids to the development of novel therapeutics for treatment of inflammation-based diseases, such as atherosclerosis and rheumatoid arthritis. The adhesion molecules ICAM-1 and VCAM-1 are known as central mediators of TEM. Clustering of these molecules by their leukocytic integrins initiates the activation of several signaling pathways within the endothelium, including a rise in intracellular Ca2+, activation of several kinase cascades, and the activation of Rho-GTPases. Activation of Rho-GTPases has been shown to control adhesion molecule clustering and the formation of apical membrane protrusions that embrace adherent leukocytes during TEM. Here, we discuss the potential regulatory mechanisms of leukocyte extravasation from an endothelial point of view, with specific focus on the role of the Rho-GTPases. 相似文献
20.
Leukocyte transendothelial migration (TEM) is one of the crucial steps during inflammation. A better understanding of the key molecules that regulate leukocyte extravasation aids to the development of novel therapeutics for treatment of inflammation-based diseases, such as atherosclerosis and rheumatoid arthritis. The adhesion molecules ICAM-1 and VCAM-1 are known as central mediators of TEM. Clustering of these molecules by their leukocytic integrins initiates the activation of several signaling pathways within the endothelium, including a rise in intracellular Ca2+, activation of several kinase cascades, and the activation of Rho-GTPases. Activation of Rho-GTPases has been shown to control adhesion molecule clustering and the formation of apical membrane protrusions that embrace adherent leukocytes during TEM. Here, we discuss the potential regulatory mechanisms of leukocyte extravasation from an endothelial point of view, with specific focus on the role of the Rho-GTPases. 相似文献