1,721,023 research outputs found
Role of the B1 Bradykinin Receptor and gC1qR/p33 in Angioedema
No full textPatients affected by angioedema (AE) are subject to asymmetric, nonerythematous, nonpruritic, localized, transient, episodic swelling of deeper layers or submucosal tissues of the skin, oropharyngolaryngeal tissue, and/or gastrointestinal wall. The nonapeptide bradykinin (BK) may be largely responsible for the vascular permeability seen in most AE. During AE attacks, activation of the serine proteases leads to the release of BK. Enzymes expressed on the endothelial cell membrane can metabolize BK, producing the agonist of the B1R, which can then be upregulated by proinflammatory stimuli, suggesting that the blockade of B1R and B2R, or gC1q/p33, may provide novel therapeutic targets
Endothelial cells are a target of both complement and kinin system.
No full textThe endothelium is a continuous physical barrier that regulates coagulation and selective passage of soluble molecules and circulating cells through the vessel wall into the tissue. Endothelial cells may contact components of the complement, the kinin and the coagulation systems and their functional activity can be influenced by these interactions. Therefore, complement activation products can induce pro-inflammatory and pro-coagulant responses by endothelial cells. Moreover complement can regulate the release of kinins on the endothelial cell surface influencing the vascular leakage. The aim of this review is to discuss the complex interplay that can be established among the endothelium, the complement proteins or its activation products, and the kinin system
Emerging Roles of the Complement System at Foeto-maternal Interface
No full textThe complement system is one of the major components of humoral innate immunity, acting as one of the first lines of defence against microbes, but new roles in inflammatory and immunological processes are emerging. The placenta undergoes
an intense process of tissue remodelling which leads to the activation of the complement (C) system resulting in the release of potentially destructive activation products that need to be neutralized. The protection of the foetus against maternal C activation products is achieved by the surface expression of regulators. The liver is the main source of the plasma C components although extra-hepatic synthesis in several tissues and organs has been documented. The data collected recently indicate that trophoblast cells are able to secrete C3 and C4 and the recognition molecule C1q, contributing to the local synthesis at the placental level. Besides trophoblast cells, decidual endothelial cells acquire the ability to synthesize and express C1q on the cell surface. All these observations support the role of C1q in the placental development and its importance in trophoblast endovascular and interstitial invasion. In conclusion it is increasingly evident that a new role of complement and in particular C1q in the processes of tissue homeostasis as well as is in inflammation and infection is now emerging
Roles and Clinical Applications of OPG and TRAIL as Biomarkers in Cardiovascular Disease
Full text linkCardiovascular diseases (CVD) remain the major cause of death and premature disability in Western societies. Assessing the risk of CVD is an important aspect in clinical decision-making. Among the growing number of molecules that are studied for their potential utility as CVD biomarkers, a lot of attention has been focused on osteoprotegerin (OPG) and its ligands, which are receptor activator of nuclear factor κB ligand (RANKL) and TNF-related apoptosis-inducing ligand. Based on the existing literature and on our experience in this field, here we review what the possible roles of OPG and TRAIL in CVD are and their potential utility as CVD biomarkers
The complement system at the embryo implantation site: friend or foe?
No full textAn inflammatory-like process and vascular remodeling represent the main changes that occur in decidua in the early phase of pregnancy. These changes are partly induced by trophoblast cells that colonize the decidua and are also contributed by the complement system. C1q is one of the component components produced at feto-maternal interface that serves an important function in placental development. Decidual endothelial cells synthesize and express C1q on the cell surface where it acts as a molecular bridge between endovascular trophoblast and endothelial cells. C1q is also produced by extravillous trophoblast and is used to favor trophoblast migration through the decidua. C7 is another component produced and expressed on the membrane of endothelial cells and is involved in the control of the proinflammatory effect of the terminal complement complex. Defective expression of C1q by trophoblast is associated with impaired trophoblast invasion of decidua and may have important implications in pregnancy disorders such as preeclampsia characterized by reduced vascular remodeling. Local control of complement activation by several complement regulators including cell-bound C7 is critical to prevent complement-mediated tissue damage as suggested by recent data showing an association of preeclampsia with mutations in the genes encoding for some complement regulators
Tanshinone VI inhibits the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1.
No full textAbstract
This study investigated the possible antitumor mechanisms of action of Tanshinone VI, one of the components of Salvia miltiorrhiza Bunge, which is used in traditional Chinese herbal medicine. To this end, the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), were evaluated in-vitroin tumor necrosis factor-alpha (TNF-alpha)-stimulated endothelial cells, with, or without the addition of Tanshinone VI (10, 20, 30, or 40 mM) in the culture medium; the effects of Tanshinone VI on angiogenesis was also evaluated with an epithelial cell tube formation assay and its toxicity was evaluated with a colorimetric (MTT) cell viability assay. The results showed that the up-regulation of ICAM-1 and VCAM-1 induced by TNF-alpha was dose-dependently inhibited by Tanshinone VI, with restoration of control levels at the dose of 40 mM; Tanshinone VI also had a remarkable anti-angiogenesis effect, already at the dose of 10 mM, while none of the doses tested had significant effects on cell viability. These results indicate that the antitumor properties of Tanshinone VI can be ascribed to the inhibition of cell adhesion, due to blockage of the up-regulation of cell adhesion molecules, with the consequent inhibition of metastases formation and/or angiogenesis. The lack of toxic effects at the dosage used makes Tanshinone VI a good candidate for its therapeutic use in humans
Feto-maternal immune interaction at the placental level
No full textA special interaction is established during pregnancy between the maternal immune
system and fetal cells to allow the survival and the normal growth of the fetus.
Fetal cells expressing paternal alloantigens are not recognized as foreign by the
mother because of an efficient anatomic barrier and a local immunosuppression
determined by the interplay of locally produced cytokines, biologically active
molecules and hormones. A special balance between TH1 and TH2 lymphocytes has
also been observed at the feto-maternal barrier that contribute to control the
immune response at this level. An important role is played by trophoblast cells
that act as a physical barrier forming a continuous layer and exert
immunomodulatory function. Trophoblast cells have also been shown to express
regulators of the complement system and to downregulate the expression of HLA
antigens. Dysfunction of these cells leads to morphological and functional
alterations of the feto-maternal barrier as well as to hormonal and immune
imbalance and may contribute to the development of pathologic conditions of
pregnancy, such as recurrent spontaneous abortions. Efforts are still needed to
better understand the physiology of the feto-maternal interaction and the
pathogenetic mechanisms responsible for tissue damage in pathologic conditions of
pregnancy
Cross-talk between the complement and the kinin system in vascular permeability
No full textThe endothelium is a continuous physical barrier that regulates coagulation and selective passage of soluble molecules and circulating cells through the vessel wall into the tissue. Due to its anatomic localization, the endothelium may establish contact with components of the complement, the kinin and the coagulation systems which are the main, though not exclusive, inducers of vascular leakage. Although the complement and the kinin systems may act independently, increasing evidence suggest that there is a crosstalk that involve different components of both systems. Activation is required for the function of the two systems which are involved in pathological conditions such as hereditary and acquired angioedema (AE) and vasculitidis. The aim of this review is to discuss the contribution of complement and kinin systems to vascular leakage and the cross-talk between the two systems in the development of AE. This clinical condition is characterized by episodic and recurrent local edema of subcutaneous and submucosal tissues and is due to inherited or acquired C1-INH deficiency. Although the pathogenesis of the swelling in patients with AE was originally thought to be mediated by C2, ample evidence indicate bradykinin (BK) as the most effective mediator even though the possibility that both the complement and the kinin-forming systems may contribute to the edema has not been completely excluded. BK induces endothelial leakage interacting with B2 receptors but other molecules may be involved in the onset and maintenance of AE. In this review we shall discuss the role of B1 receptors and gC1qR/p33 in addition to that of B2 receptors in the onset of AE attacks and the importance of these receptors as new possible molecular targets for therapy
Dyslipidemia and Diabetes Increase the OPG/TRAIL Ratio in the Cardiovascular System
Full text linkBackground. Dyslipidemia and diabetes are two of the most well established risk factors for the development of cardiovascular disease (CVD). Both of them usually activate a complex range of pathogenic pathways leading to organ damage. Here we hypothesized that dyslipidemia and diabetes could affect osteoprotegerin (OPG) and TNF-related apoptosis-inducing ligand (TRAIL) expression in the vessels and the heart. Materials and Methods. Gene and protein expression of OPG, TRAIL, and OPG/TRAIL ratio were quantified in the aorta and the hearts of control mice, dyslipidemic mice, and diabetic mice. Results. Diabetes significantly increased OPG and the OPG/TRAIL ratio expression in the aorta, while dyslipidemia was the major determinant of the changes observed in the heart, where it significantly increased OPG and reduced TRAIL expression, thus increasing cardiac OPG/TRAIL ratio. Conclusions. This work shows that both dyslipidemia and diabetes affect OPG/TRAIL ratio in the cardiovascular system. This could contribute to the changes in circulating OPG/TRAIL which are observed in patients with diabetes and CVD. Most importantly, these changes could mediate/contribute to atherosclerosis development and cardiac remodeling
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