scholarly journals Defensin Stimulates the Binding of Lipoprotein (a) to Human Vascular Endothelial and Smooth Muscle Cells

Blood ◽  
1997 ◽  
Vol 89 (12) ◽  
pp. 4290-4298 ◽  
Author(s):  
Abd Al-Roof Higazi ◽  
Ehud Lavi ◽  
Khalil Bdeir ◽  
Anthony M. Ulrich ◽  
Dara G. Jamieson ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cerebral Arteries ◽  
Muscle Cells ◽  
Tissue Type ◽  
Vascular Endothelial ◽  
Atherosclerotic Vascular Disease ◽  
Lipoprotein A ◽  
Type Plasminogen Activator

AbstractThere is evidence to suggest that elevated plasma levels of lipoprotein (a) [Lp(a)] represent a risk factor for the development of atherosclerotic vascular disease, but the mechanism by which this lipoprotein localizes to involved vessels is only partially understood. In view of studies suggesting a link between inflammation and atherosclerosis and our previous finding that leukocyte defensin modulates the interaction of plasminogen and tissue-type plasminogen activator with cultured human endothelial cells, we examined the effect of this peptide on the binding of Lp(a) to cultured vascular endothelium and vascular smooth muscle cells. Defensin increased the binding of Lp(a) to endothelial cells approximately fourfold and to smooth muscle cells approximately sixfold. Defensin caused a comparable increase in the amount of Lp(a) internalized by each cell type, but Lp(a) internalized as a consequence of defensin being present was not degraded, resulting in a marked increase in the total amount of cell-associated lipoprotein. Abundant defensin was found in endothelium and in intimal smooth muscle cells of atherosclerotic human cerebral arteries, regions also invested with Lp(a). These studies suggest that defensin released from activated or senescent neutrophils may contribute to the localization and persistence of Lp(a) in human vessels and thereby predispose to the development of atherosclerosis.

scholarly journals Lipoprotein(a) in Cardiovascular Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Michele Malaguarnera ◽  
Marco Vacante ◽  
Cristina Russo ◽  
Giulia Malaguarnera ◽  
Tijana Antic ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Risk Factor ◽  
Cardiovascular Diseases ◽  
Smooth Muscle Cells ◽  
Bypass Graft ◽  
Muscle Cells ◽  
Tissue Type ◽  
Apo B ◽  
Lipoprotein A

Lipoprotein(a) (Lp(a)) is an LDL-like molecule consisting of an apolipoprotein B-100 (apo(B-100)) particle attached by a disulphide bridge to apo(a). Many observations have pointed out that Lp(a) levels may be a risk factor for cardiovascular diseases. Lp(a) inhibits the activation of transforming growth factor (TGF) and contributes to the growth of arterial atherosclerotic lesions by promoting the proliferation of vascular smooth muscle cells and the migration of smooth muscle cells to endothelial cells. Moreover Lp(a) inhibits plasminogen binding to the surfaces of endothelial cells and decreases the activity of fibrin-dependent tissue-type plasminogen activator. Lp(a) may act as a proinflammatory mediator that augments the lesion formation in atherosclerotic plaques. Elevated serum Lp(a) is an independent predictor of coronary artery disease and myocardial infarction. Furthermore, Lp(a) levels should be a marker of restenosis after percutaneous transluminal coronary angioplasty, saphenous vein bypass graft atherosclerosis, and accelerated coronary atherosclerosis of cardiac transplantation. Finally, the possibility that Lp(a) may be a risk factor for ischemic stroke has been assessed in several studies. Recent findings suggest that Lp(a)-lowering therapy might be beneficial in patients with high Lp(a) levels. A future therapeutic approach could include apheresis in high-risk patients in order to reduce major coronary events.

Release of Soluble Urokinase Receptor from Vascular Cells*

2001 ◽  
Vol 86 (08) ◽  
pp. 686-693 ◽  
Author(s):  
Triantafyllos Chavakis ◽  
Antje Willuweit ◽  
Florea Lupu ◽  
Klaus Preissner ◽  
Sandip Kanse
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Urokinase Receptor ◽  
Platelet Derived Growth Factor ◽  
Vascular Endothelial ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator

SummaryUrokinase-type plasminogen activator (uPA) and its cell surface-receptor (uPAR) regulate cellular functions linked to adhesion and migration and contribute to pericellular proteolysis in tissue remodelling processes. Soluble uPAR (suPAR) is present in the circulation, peritoneal and ascitic fluid and in the cystic fluid from ovarian cancer. We have investigated the origin and the vascular distribution of the soluble receptor, which accounts for 10-20% of the total receptor in vascular endothelial and smooth muscle cells. Phase separation analysis of the cell conditioned media with Triton X-114 indicated that suPAR associates with the aqueous phase, indicative of the absence of the glycolipid anchor. There was a polarized release of suPAR from cultured endothelial cells towards the basolateral direction, whereas the membrane-bound receptor was found preferentially on the apical surface. Both, uPAR and suPAR became upregulated 2-4 fold after activation of protein kinase C with phorbol ester, which required de-novo protein biosynthesis. Interleukin-1β (IL-1β), basic fibroblast growth factor (bFGF) or vascular endothelial growth factor increased suPAR release from endothelial cells, whereas platelet derived growth factor-BB, bFGF or IL-1β stimulated suPAR release from vascular smooth muscle cells. Immune electron microscopy indicated that in atherosclerotic vessels (s)uPAR was observed on cell membranes as well as in the extracellular matrix. These findings indicate that (s)uPAR from vascular cells is upregulated by proangiogenic as well as proatherogenic growth factors and cytokines, is preferentially released towards the basolateral side of endothelial cells and accumulates in the vessel wall.*Part of this work was supported by grants (Pr 327/1-4) from the Deutsche Forschungsgemeinschaft (Bonn, Germany) and the Novartis-Foundation (Nürnberg, Germany). This work is part of the MD/PhD-thesis of T.C. at the Institute for Biochemistry, Department of Medicine, Justus-Liebig-Universität, Giessen, Germany. Abbreviations: bFGF: basic fibroblast growth factor, GPI: glycosyl-phosphatidylinositol, FCS: fetal calf serum, HUVEC: human umbilical vein endothelial cells, HVSMC: human vascular smooth muscle cells, IL-1β: interleukin-1β, mAb: monoclonal antibody, PBS: phosphate-buffered saline, PDGF-BB: platelet derived growth factor-BB, piPLC: phosphatidylinositol-specific phospholipase C, piPLD: phosphatidylinositol-specific phospholipase D, PMA: phorbol myristate acetate, scuPA: single chain uPA, suPAR: soluble urokinase receptor, uPA: urokinase- type plasminogen activator, uPAR: urokinase receptor, VN: vitronectin

scholarly journals Inhibitory effect of caveolin-1 in vascular endothelial cells, pericytes and smooth muscle cells

Oncotarget ◽  
2017 ◽  
Vol 8 (44) ◽  
pp. 76165-76173 ◽  
Author(s):  
Hongping Xu ◽  
Liwei Zhang ◽  
Wei Chen ◽  
Jiazhou Xu ◽  
Ruting Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Endothelial Cells ◽  
Muscle Cells ◽  
Inhibitory Effect ◽  
Vascular Endothelial ◽  
Caveolin 1

scholarly journals IL-8 reduces VCAM-1 secretion of smooth muscle cells by increasing p-ERK expression when 3-D co-cultured with vascular endothelial cells

2011 ◽  
Vol 34 (3) ◽  
pp. 138 ◽  
Author(s):  
Zhi Zhang ◽  
Guang Chu ◽  
Hong-Xian Wu ◽  
Ni Zou ◽  
Bao-Gui Sun ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Type I Collagen ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Muscle Cells ◽  
Type I ◽  
Vascular Endothelial ◽  
Culture Model

Objective: The goal of this study was to investigate the crosstalk between vascular endothelial cells (ECs) and smooth muscle cells (SMCs) using a three-dimensional (3-D) co-culture model. In addition, the role of IL-8 in this crosstalk was investigated. Methods: A 3-D co-culture model was constructed using a Transwell chamber system and type I collagen gel. Human umbilical artery smooth muscle cells (HUASMCs) were suspended in the gel and added to the upper compartment of the Transwell. Human umbilical vein endothelial cells (HUVECs) were then grown on the surface of the gel. The growth of HUASMCs was tested with a CFDA SE cell proliferation kit. IL-8 and other bioactive substances were investigated by ELISA and real-time PCR. The alteration of p-ERK expression related to the change in IL-8 levels was also examined by Western blot analysis. Results: The proliferation rate of HUASMCs in the 3-D co-culture model was 0.679 ± 0.057. Secretion and transcription of VEGF, t-PA, NO and VCAM-1 in the 3-D co-culture model were different than in single (2-D) culture. When 3-D co-cultured, IL-8 released by HUVECs was significantly increased (2.35 ± 0.16 fold) (P﹤0.05) and the expression of VCAM-1 from HUASMCs was reduced accordingly (0.55±0.09 fold). In addition, increasing or decreasing the level of IL-8 changed the level of p-ERK and VCAM-1 expression. The reduction of VCAM-1, resulting from increased IL-8, could be blocked by the MEK inhibitor, PD98059. Conclusion: Crosstalk between HUVECs and HUASMCs occurred and was probably mediated by IL-8 in this 3-D co-culture model.

ADENINE NUCLEOTIDES AND THEREGULATION OF VASCULAR TONE

1987 ◽  
Author(s):  
J L Gordon
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Blood Vessels ◽  
Vascular Tone ◽  
Adenine Nucleotides ◽  
Muscle Cells ◽  
Vascular Endothelial ◽  
Atp Analogs ◽  
Vascular Beds

ATP, although known mainly as an intracellular energy source, is also capable of acting extracellularly as a vasoactive agent of great potency, at concentrations around lμM or less. ADP is approximately equipotent with ATP in its actions on extracellular receptors in the vasculature.ATP and ADP can arise extracellularly through release from the cytoplasm of cellsexposed to damaging stimuli or by degranulation of platelets. The concentration of the nucleotides in the cytoplasm of most cells (including vascular endothelial and smooth muscle cells) is more than ImM, and the concentration in the dense storage granules of platelets approaches 1M. Thus, there is potential for very high localised concentrations of ATP and ADP in the plasma following platelet degranulation or damageto cells of the vessel well. Release from vascular endothelial and smooth muscle cells can occur with no loss of cell viability or leakage of cytoplasmic proteins.The vasoactivity of ATP and ADP is mediated via P2 purinoceptors. Vasodilation can be induced through the release of EDRF from endothelial cells or through stimulation of PGI2 production (PGI2 is a vasodilator in many, althoughnot all, arterial beds). Purinoceptor-mediated prostacyclin production can be stimulated from perfused vascular beds (e.g. theheart andthe lung), from isolated blood vessels or from cultured endothelial cells.In some blood vessels, purinoceptor-mediated vasoconstriction can be induced by direct actionon the vascular smooth muscle cells. The receptors responsible are sub-classified as P2X (which induce vasoconstriction) and P2Y (whichinduce vasodilation). The P2Y purinoceptor that mediates EDRF production is very similar to that which is responsible for PGI2 production, although there are some intriguing differences inthe potency of ATP analogs at stimulating these two responses, even on the same cells. The intracellular mechanisms responsible have not yet been fully elucidated, but it appears that elevation of intracellular calcium is likely to play a causal role.Adenosine, which is the product of ATP and ADP metabolism by nucleotidases, can also induce vasodilation in many blood vessels, acting via P1] purinoceptors on the smooth muscle cells, but its potency is often less than that of ATP and ADP.The fate of adenine nucleotides released into the plasma is determined by ectonucleotidases on the luminal surface of the endothelial cells, not by enzymes in the blood itself (the half-life of ATP in samples of blood or plasma is many minutes, while in the microcirculation the half-life isless than one second). Endothelial ectonucleotidases have been detected in several vascular beds, and many of their characteristics are now known. These enzymes are distinct entities from the P2 purinoceptors on endothelium, as shown by the marked differences in potency of several ATP analogs as P2 receptor stimulants and as substrates for the nucleotidases.In summary, vascular endothelial and smooth muscle cells respond to extracellularATP and ADP, and can also metabolise thesenucleotides extracellularly by ectonucleotidases. In addition, ATP and ADP can be selectively released from the cells of the vessel wall and from activated platelets. Thus, the endothelial pericellular environment can be the site of complex interactions by which vascular tone is regulated through the release, actions and metabolism ofextracellular nucleotides.

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