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Thromb Haemost 2004; 91(04): 755-760
DOI: 10.1160/TH03-09-0602
Platelets and Blood Cells
Schattauer GmbH

Activated human platelets release connective tissue growth factor

Iwona Cicha
1   Medical Clinic IV, University of Erlangen-Nuremberg, Erlangen, Germany
,
Christoph D. Garlichs
2   Medical Clinic II, University of Erlangen-Nuremberg, Erlangen, Germany
,
Werner G. Daniel
2   Medical Clinic II, University of Erlangen-Nuremberg, Erlangen, Germany
,
Margarete Goppelt-Struebe
1   Medical Clinic IV, University of Erlangen-Nuremberg, Erlangen, Germany
› Author AffiliationsFinancial support: This work was supported by a grant from Deutsche Forschungsgemeinschaft, GRK 750. Iwona Cicha is a recipient of GRK 750 fellowship.
Further Information

Publication History

Received 26 September 2003

Accepted after revision 14 January 2004

Publication Date:
06 December 2017 (online)

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Summary

Connective tissue growth factor (CTGF) is overexpressed in wound healing, fibrosis and advanced atherosclerotic lesions. Platelets adhere to CTGF, suggesting that this protein may be involved in the formation of platelet-rich thrombi at the sites of tissue injury or atherosclerotic plaque rupture. Since platelets contain a wide array of biologically active proteins, we investigated the presence, localization and release of CTGF from these cells. For this purpose, human platelets from healthy donors were washed and stimulated with thrombin or ADP. Following incubation, proteins from unstimulated and stimulated cell lysates and the supernatants were analysed by Western blotting. The experiments showed that unstimulated platelets contain considerable amounts of CTGF, whereas no CTGF was detectable in platelet-poor plasma. To elucidate the origin of CTGF in platelets, we performed immunohistochemical analysis of human bone marrow sections. The analysis showed that although CTGF protein is widely expressed in bone marrow cells, it is not expressed by platelet-producing megakaryocytes, suggesting that CTGF presence in platelets is a result of endocytosis from extracellular environment in bone marrow. Agonist-stimulation of platelets resulted in a significant release of CTGF from the storage granules, with thrombin at 0.1 U/mL being a more potent activator than ADP at 20 µmol/L. The agonist-dependent CTGF secretion was significantly inhibited by aspirin. In conclusion, CTGF is stored in normal human platelets, and can be released upon platelet activation. Aspirin treatment prevents CTGF release, suggesting that clinical benefits of this drug may involve the inhibition of CTGF secretion.

Keywords

Platelets - connective tissue growth factor - atherosclerosis
 

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