Platelets contain a peptide inhibitor of endothelial cell replication and growth.
Platelets release specific growth factors that stimulate division of aortic endothelial cells. Acidification or heating to 56 degrees C of platelet extracts is required to detect these factors. Nonheated platelet extracts inhibit endothelial growth. To determine if this inhibitory effect is due to a discrete chemical substance, a crude extract obtained by freezing and thawing human platelets was incubated with an endothelial cell mitogen and found to inhibit the endothelial cell incorporation of [3H]thymidine by greater than 95%. The inhibitor was partially purified by ion-exchange and gel-filtration chromatography. The partially purified material inhibited endothelial cell division as well as DNA synthesis. Inhibition caused by the partially purified material was concentration dependent, reversible, and not due to cytotoxicity. Further purification by heparin-Sepharose chromatography resulted in removal of greater than 95% of the contaminating substances without a loss of inhibitory activity. Physical characterization revealed that heparin-Sepharose-purified factor was heat labile, had a molecular size estimated at 35-40 kDa, and was stable between pH 4.5 and 9.0. Treatment with proteolytic enzymes destroyed all biologic activity, suggesting a peptide composition. These data support the conclusion that platelets contain a potent inhibitor of endothelial replication and growth. Since platelet deposition and release occur after endothelial denudation, release of this platelet-derived growth inhibitor may be an important regulator of reendothelialization that occurs after vessel injury.
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002453:Cell Cycle; D003470:Culture Media; D003594:Cytoplasmic Granules / Q000032:analysis; D004727:Endothelium / Q000166:cytology*; D006131:Growth Inhibitors / Q000302:isolation & purification*; D006358:Hot Temperature; D006801:Humans; D007526:Isoelectric Point; D008970:Molecular Weight; D010447:Peptide Hydrolases / Q000378:metabolism; D013552:Swine
D003470:Culture Media; D006131:Growth Inhibitors; D010447:Peptide Hydrolases