Association of smooth muscle cell tissue factor with caveolae

Mulder, AB; Smit, Jw; Bom, Vjj; Blom, Nel R.; Ruiters, Marcel H. J.; Halie,; vanderMeer, J

doi:10.1182/blood.v88.4.1306.bloodjournal8841306

Cited by 67 publications

(36 citation statements)

References 45 publications

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“…Moreover, Mulder et al . () utilized immunogold‐labelling to locate TF in intracellular lysosome‐like structures that exhibited high morphological resemblance to MVBs with intraluminal exosomes. Thus these data suggest that TF can be loaded into exosomes originating from VSMC MVBs.…”

Section: Exosomes Released From Vascular Smooth Cells Mediate Calcifimentioning

confidence: 99%

Emerging roles for vascular smooth muscle cell exosomes in calcification and coagulation

Kapustin

Shanahan

2016

The Journal of Physiology

125

108

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Vascular smooth muscle cell (VSMC) phenotypic conversion from a contractile to ‘synthetic’ state contributes to vascular pathologies including restenosis, atherosclerosis and vascular calcification. We have recently found that the secretion of exosomes is a feature of ‘synthetic’ VSMCs and that exosomes are novel players in vascular repair processes as well as pathological vascular thrombosis and calcification. Pro‐inflammatory cytokines and growth factors as well as mineral imbalance stimulate exosome secretion by VSMCs, most likely by the activation of sphingomyelin phosphodiesterase 3 (SMPD3) and cytoskeletal remodelling. Calcium stress induces dramatic changes in VSMC exosome composition and accumulation of phosphatidylserine (PS), annexin A6 and matrix metalloproteinase‐2, which converts exosomes into a nidus for calcification. In addition, by presenting PS, VSMC exosomes can also provide the catalytic surface for the activation of coagulation factors. Recent data showing that VSMC exosomes are loaded with proteins and miRNA regulating cell adhesion and migration highlight VSMC exosomes as potentially important communication messengers in vascular repair. Thus, the identification of signalling pathways regulating VSMC exosome secretion, including activation of SMPD3 and cytoskeletal rearrangements, opens up novel avenues for a deeper understanding of vascular remodelling processes.

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Section: Exosomes Released From Vascular Smooth Cells Mediate Calcifimentioning

confidence: 99%

Emerging roles for vascular smooth muscle cell exosomes in calcification and coagulation

Kapustin

Shanahan

2016

The Journal of Physiology

125

108

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“…Ultrastructural localization of TF in a variety of cell types showed that a fraction of the TF in these cells is associated with caveolae, a specialized membrane domain rich in cholesterol-and sphingolipid-rich rafts. [84][85][86][87]. Mulder et al [84] speculated that the caveolae-associated TF represents the encrypted form, which can rapidly be activated at sites in which vessel wall integrity is lost.…”

Section: (V) Protein Disulfide Isomerase: Regulation Of Tf Activity Bmentioning

confidence: 99%

Tissue factor mechanisms of decryption

Rao¹

2012

Front Biosci

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Tissue factor (TF) is a cellular receptor for clotting factor VII/VIIa (FVII/FVIIa). Formation of TF-FVIIa complexes on cell surfaces not only triggers the coagulation cascade but also transduces cell signaling via activation of protease-activated receptors. It is generally believed that only a small fraction of the TF found on cell surfaces is active in coagulation whereas the vast majority is cryptic (non-functional) in coagulation. It is unclear how cryptic TF differs from the coagulant active TF or potential mechanisms involved in transformation of cryptic TF to the coagulant active form. Both cryptic and coagulant active TF forms can bind FVIIa. It is generally believed that cryptic TF-FVIIa complexes fail to activate factor X as the protein substrate binding site is buried in the encrypted complex and a change in TF-FVIIa complex that exposes the substrate binding site leads to its decryption. Exposure of phosphatidylserine (PS) in response to various chemical or pathophysiological stimuli has been considered as the most potent inducer of TF decryption. In addition to PS, TF self-association and association with specialized membrane domains may also play a role in TF decryption. Recent studies suggest that cryptic form of TF contains unpaired cysteine thiols at Cys186 and Cys209 in the membrane-proximal domain, whereas the coagulant active form of TF is thought to have an oxidized Cys186-Cys209 disulfide bond. It has been suggested that protein disulfide isomerase (PDI) regulates TF decryption through its oxidoreductase activity by targeting this disulfide bond or regulating the PS equilibrium at the plasma membrane. However, this hypothesis requires further validation to become an accepted mechanism. In this article, we critically review literature on TF encryption/decryption with specific emphasis on recently published data and provide our perspective on this subject.

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“…It has been reported that TF exists in the cell membrane of smooth muscle cells inside invaginations or caveolae. 23 This encrypted TF is suggested to be a latent pool of coagulant TF. If this were indeed the mechanism of encryption, it could explain the activation of TF after lysis or freeze-thawing in the previous study, for this would open up these caveolae and expose the hidden TF.…”

Section: Encrypted Tfmentioning

confidence: 99%

Tissue Factor on the Loose

Giesen¹,

Nemerson²

2000

Semin Thromb Hemost

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The enzymatic complex of tissue factor (TF) and the blood coagulation factor VIIa is generally considered to be the initiator of coagulation. Coagulation that occurs at the site of luminal injury to an artery is, along with platelet deposition, the cause of arterial thrombosis, which is the leading cause of death in Western society. Under pathological conditions the intima, the neointima and the atherosclerotic plaque contain active TF. Therefore the initiation of thrombosis is believed to be due to TF present in the wall of the pathologically changed artery. This classical view of thrombosis has been challenged. In this article we review the evidence for the presence of TF activity in various tissues outside the vessel wall, in extracellular form, in encrypted form, and even in plasma. We found TF expression in a variety of cells in culture after growth factor or cytokine stimulation. This TF was often also present in the extracellular matrix, and in addition we found latent TF on the outside of unbroken smooth muscle cells. Freeze-thawing the cells or detergent lysis could activate this TF. We also found TF activity in native whole blood and in plasma. Inhibition of this circulating TF prevented formation of thrombi on collagen-coated glass slides in an ex vivo perfusion system. Furthermore, in a thrombosis model in which rat aorta was injured, TF was found on the intimal surface of the injured aorta. TF activity was measured in a flow chamber, and it was shown that all measurable activity was extracellular. We conclude that blood-borne TF plays a major role in thrombosis. Encryption of TF present in circulation could be a mechanism that prevents thrombosis. Alternatively, circulating TF may be active but below the threshold required for the initiation of blood coagulation.

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Association of smooth muscle cell tissue factor with caveolae

Cited by 67 publications

References 45 publications

Emerging roles for vascular smooth muscle cell exosomes in calcification and coagulation

Emerging roles for vascular smooth muscle cell exosomes in calcification and coagulation

Tissue factor mechanisms of decryption

Tissue Factor on the Loose

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