Low‐density lipoproteins increase intracellular calcium in aequorin‐loaded platelets

Dunn, R. C.; Schachter, Mike; Miles, C. M. M.; Fehér, M; Tranter, Pamela; Bruckdorfer, K. Richard; Sever, Peter

doi:10.1016/0014-5793(88)80512-x

Cited by 32 publications

(8 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…LDL enhanced fibrinogen binding by ADP 8 ; aggregation, thromboxane A 2 formation, and serotonin secretion by thrombin 9,10 ; and platelet responsiveness to epinephrine and Ca 2ϩ -ionophore. 11 Acting as an independent agonist, very low concentrations of LDL (10 mg protein/L) induced a rise in cytosolic Ca 2ϩ and inositol phosphate turnover, 12,13 physiological concentrations induced changes in shape (0.25 to 0.5 g/L) and aggregation (Ն0.75 g/L), 14 and, at concentrations Ͼ3 g/L, LDL triggered phosphorylation of pleckstrin, the 47-kDa substrate of protein kinase C (PKC). 15 Apart from receptor-mediated signaling, LDL may affect platelets by lipid exchange.…”

mentioning

confidence: 99%

Low-Density Lipoprotein Enhances Platelet Secretion Via Integrin-α _IIb β ₃ –Mediated Signaling

Hackeng

Huigsloot

Pladet

et al. 1999

ATVB

View full text Add to dashboard Cite

Abstract-LDL is known to increase the sensitivity of human platelets for agonists and to induce aggregation and secretion independently at high concentrations, but its mechanism of action is largely obscure. To clarify how LDL increases platelet sensitivity, cells were incubated in lipoprotein-poor plasma and treated with collagen at a concentration that induced Ϸ20% secretion of 14 C-serotonin. Preincubation with LDL (30 minutes at 37°C) enhanced secretion in a dose-dependent manner to 60Ϯ14% at a concentration of 2 g LDL protein/L. Similar stimulation by LDL was seen when secretion was induced by the thrombin receptor-activating peptide. This enhancement was strongly reduced (1)

show abstract

mentioning

confidence: 99%

Low-Density Lipoprotein Enhances Platelet Secretion Via Integrin-α _IIb β ₃ –Mediated Signaling

Hackeng

Huigsloot

Pladet

et al. 1999

ATVB

View full text Add to dashboard Cite

show abstract

“…At physiological and higher concentrations, LDLs induce changes in platelet cell shape and aggregation, activate integrin ␣ IIb␤3 -mediated signaling, and triggered the PKC-dependent phosphorylation of pleckstrin. [15][16][17] The data of Rodríguez et al 6,18 indicate that also endothelial cells respond to LDL at physiological and higher concentrations. At present, it is unknown how the LDL particle transduces its signal into the cell.…”

Section: See Page 1409mentioning

confidence: 99%

Lysyl Oxidase

Bank

Hinsbergh

2002

ATVB

View full text Add to dashboard Cite

T he extracellular matrix proteins collagen and elastin determine, to a large extent, the biomechanical properties of the vessel wall. Both molecules are secreted as monomers, but are posttranslationally modified in the extracellular space in order to generate stable polymers. A critical feature of collagen and elastin fibers is the degree of cross-linking. The first step in cross-linking is the oxidative deamination of the ⑀-amino group of certain peptidyl (hydroxy)lysyl residues, resulting in the aldehyde (hydroxy)allysine. In collagen, (hydroxy)allysine is restricted to the Cand N-telopeptide. The aldehyde reacts with a lysyl (Lys) or hydroxylysyl (Hyl) residue in the triple helix, resulting in a variety of cross-links. 1 In elastin, the oxidative deamination of Lys (Hyl is absent in elastin) is less restrictive, resulting in modification of most of the Lys residues. Well known elastin cross-links are lysinonorleucine and the pyridiniums desmosine and isodesmosine. 1 The cross-links in collagen are responsible for the stiffness of collagen fibers, 2 whereas the cross-links in elastin are important for the rubber-like properties of elastin fibers. 3 See page 1409The enzyme responsible for the oxidative deamination of the ⑀-amino groups is lysyl oxidase (LOX), a copperdependent amine oxidase. 4 Reduced activity levels of this enzyme result in decreased degree of cross-linking, affecting the biomechanical properties of extracellular matrices 2 as well as the susceptibility of collagen and elastin to degradation by proteinases. 5 In this issue, Rodríguez et al 6 describe the downregulation of LOX expression in porcine endothelial cells subjected to atherogenic levels of LDL. The authors hypothesize that this results in a decreased degree of elastin and/or collagen cross-linking, which leads to alterations in the integrity of the extracellular matrix and thereby enhances endothelial permeability. This is an interesting hypothesis that points to the intimate interaction between the cell matrix and cell functioning. It shows resemblance with the increased endothelial permeability found in diabetic vessels, which is also accompanied by alterations in the extracellular matrix. This attractive idea asks for further testing. For example, apart from LOX, four more LOX-like genes have recently been cloned (LOXL1 to 4). 7 The substrate specificity of these enzymes in vivo is hardly known, as is the expression in endothelial cells. It is likely that at least some of them are involved in cross-linking, 8,9 and at this stage, it cannot be excluded that they are able to compensate for the decrease of LOX expression levels in the model described by Rodríguez et al. 6 Multiple novel biological functions have recently been attributed to LOX, such as suppressing the ras oncogene, being a stimulator of collagen type III promotor activity, playing a role in cell adhesion and growth control, 4,10 and acting intracellularly. 11,12 It is therefore possible that the increased endothelial permeability is due to a phenomenon other than cr...

show abstract

“…Low-density lipoproteins (LDL) have been reported to possess platelet activating activities such as the enhancement of platelet sensitivity to stimuli (1)(2)(3)(4) and the induction of platelet aggregation (5)(6). Oxidative modification dramatically changes the biological properties of LDL, converting them into a form that is both atherogenic and pro-thrombotic (7)(8).…”

Section: Introductionmentioning

confidence: 99%

“…LDL enhanced flbrinogen binding in response to, aggregation (4), thromboxane A z formation and serotonin secretion by thrombin (2,9); and platelet responsiveness to epinephrine and Ca z" -ionophore (1). Acting as an independent agonist, very low concentrations of LDL (10 rag/L) induced a rise in cytosolic Ca 2~ and inositol phosphate turnover (10-11), physiological concentrations induced changes in shape (0.25 g/L to 0.5 g/L) and aggregation (>0.75 g/ L) (6), and at concentrations >3 g/L, LDL triggered phosphorylation of pleckstrin, the 47-kDa substrate of protein kinase C (PKC) (5).…”

Section: Introductionmentioning

confidence: 99%

Interaction of LDL and platelets in ischaemic and ischaemic risk subjects

Gupta

Mallika

Srivastava

2005

Indian J Clin Biochem

View full text Add to dashboard Cite

Platelets play a vital role in the progression of atherosclerosis and thrombosis, a major cause of death worldwide. Platelets are activated by many triggers like elevated LDL in blood resulting in aggregation and formation of plaque. The purpose of this study was to investigate the effect of LDL and signal transduction inhibitor on the activation of platelets in Ischaemic risk subjects.Platelets from IHD and hyperlipidemic subjects were hypersensitive to ADP, as higher levels of platelet aggregation were observed in these groups. LDL from IHD hypedipidemic subjects was more effective in activating platelets from any other group. Ox-LDL was more effective in activating platelets than native-LDL as monitored by level of platelet aggregation induced by PAF and thrombin. Calcium channel blocker, nifedipine and verapamil inhibited platelet aggregation at micromolar level. Protein kinase inhibitor, staurosporine was effective in inhibiting ADP induced aggregation at nanomolar level.

show abstract

Low‐density lipoproteins increase intracellular calcium in aequorin‐loaded platelets

Cited by 32 publications

References 20 publications

Low-Density Lipoprotein Enhances Platelet Secretion Via Integrin-α _IIb β ₃ –Mediated Signaling

Low-Density Lipoprotein Enhances Platelet Secretion Via Integrin-α _IIb β ₃ –Mediated Signaling

Lysyl Oxidase

Interaction of LDL and platelets in ischaemic and ischaemic risk subjects

Contact Info

Product

Resources

About

Low‐density lipoproteins increase intracellular calcium in aequorin‐loaded platelets

Cited by 32 publications

References 20 publications

Low-Density Lipoprotein Enhances Platelet Secretion Via Integrin-α IIb β 3 –Mediated Signaling

Low-Density Lipoprotein Enhances Platelet Secretion Via Integrin-α IIb β 3 –Mediated Signaling

Lysyl Oxidase

Interaction of LDL and platelets in ischaemic and ischaemic risk subjects

Contact Info

Product

Resources

About

Low-Density Lipoprotein Enhances Platelet Secretion Via Integrin-α _IIb β ₃ –Mediated Signaling

Low-Density Lipoprotein Enhances Platelet Secretion Via Integrin-α _IIb β ₃ –Mediated Signaling