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Thrombin and vascular inflammation

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Abstract

Vascular endothelium is a key regulator of homeostasis. In physiological conditions it mediates vascular dilatation, prevents platelet adhesion, and inhibits thrombin generation. However, endothelial dysfunction caused by physical injury of the vascular wall, for example during balloon angioplasty, acute or chronic inflammation, such as in atherothrombosis, creates a proinflammatory environment which supports leukocyte transmigration toward inflammatory sites. At the same time, the dysfunction promotes thrombin generation, fibrin deposition, and coagulation. The serine protease thrombin plays a pivotal role in the coagulation cascade. However, thrombin is not only the key effector of coagulation cascade; it also plays a significant role in inflammatory diseases. It shows an array of effects on endothelial cells, vascular smooth muscle cells, monocytes, and platelets, all of which participate in the vascular pathophysiology such as atherothrombosis. Therefore, thrombin can be considered as an important modulatory molecule of vascular homeostasis. This review summarizes the existing evidence on the role of thrombin in vascular inflammation.

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Abbreviations

AT:

Antithrombin

APC:

Activating protein C

CCL:

Chemokine (C–C motif) ligand

cPLA2 :

Cytosolic phospholipase A2

CXCL:

Chemokine (C-X-C motif) ligand

cysLT:

Cysteinyl leukotrienes

DCs:

Dendritic cells

ECs:

Endothelial cells

EDHF:

Endothelium-derived hyperpolarizing factor

ERK:

Extracellular signal regulated kinase

EGFR:

Epidermal growth factor receptor

GPIb/IIb/IIIa:

Glycoprotein Ib/IIb/IIIa

HLA:

Human leukocyte antigen

ICAM-1:

Intercellular adhesion molecule-1

IFN-γ:

Interferon-γ

IL-1α/β:

Interleukin-1α/β

IP-10:

Inducible protein-10

LT:

Leukotriene

LPS:

Lipopolysacharide

MAPK:

Mitogen activated protein kinase

M-CSF:

Macrophage colony-stimulating factor

NO:

Nitric oxide

PAI-1:

Plasminogen activator inhibitor-1

PAR:

Protease-activated receptors

PDGF:

Platelet-derived growth factor receptor

PF4:

Platelet factor 4

PGE2 :

Prostaglandin E2

PGI2 :

Prostacyclin I2

PMN:

Polymorphonuclear leukocytes

PSGL-1:

P-selectin glycoprotein ligand-1

RANTES:

Regulated on activation, normal T expressed and secreted

TF:

Tissue factor

TGF-β:

Transforming growth factor-β

TFPI:

Tissue factor pathway inhibitor

TNF-α:

Tumor necrosis factor-α

TXA2 :

Thromboxane A2

VCAM-1:

Vascular cell adhesion molecule-1

VEGF:

Vascular endothelial growth factor

VSMCs:

Vascular smooth muscle cells

vWF:

von Willebrand factor

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Acknowledgments

This study was supported by grants: Deutsche Forschungsgemeinschaft, Si 285/7-1 (to Tatiana Syrovets and Thomas Simmet), and Serbian Government Research Grants, No. 173033 (to Esma R. Isenović) and No. 175085 (to Milan Popović).

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  1. Department for Radiobiology and Molecular Genetics, Vinča Institute, University of Belgrade, P.O. Box 522, 11001, Belgrade, Serbia

    Milan Popović, Katarina Smiljanić, Branislava Dobutović & Esma R. Isenović

  2. Institute of Pharmacology of Natural Products & Clinical Pharmacology, Ulm University, 89081, Ulm, Germany

    Tatiana Syrovets & Thomas Simmet

Authors
  1. Milan Popović
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  2. Katarina Smiljanić
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  3. Branislava Dobutović
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  4. Tatiana Syrovets
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  5. Thomas Simmet
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  6. Esma R. Isenović
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Corresponding author

Correspondence to Milan Popović.

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Popović, M., Smiljanić, K., Dobutović, B. et al. Thrombin and vascular inflammation. Mol Cell Biochem 359, 301–313 (2012). https://doi.org/10.1007/s11010-011-1024-x

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  • DOI: https://doi.org/10.1007/s11010-011-1024-x

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