Plasminogen activator inhibitor type-1 controls the process of the in vitro sprout formation

• Autorzy: Chorostowska-Wynimko J. , Skrzypczak-Jankun E. , Jankun J.
• Języki publikacji: EN

Abstrakty

EN

Plasminogen activator inhibitor type-1 (PAI-1), the primary regulator of plasminogen activator - urokinase (uPA) plays a crucial role in the cell adhesion and migration and in angiogenesis. We had previously demonstrated that PAI-1 - endothelial cell interplay is critical for the formation of new blood vessels and the process is mostly conducted via uPA- anti-proteinase interaction. In the present study we wished to further examine the role of PAI-1 in the sprout formation, representing the first step of new capillary vessels development by evaluating the effect of PAI-1 on the sprout area. We addressed the issue by assessing the influence of cysteine-mutated PAI-1 proteins characterized by a prolonged half-life time (hDßT - T1/2= 63.59 h and ßT- T1/2= 6931.47 h), and therefore more stable anti-uPA activity, on the appearance of newly formed sprouts. We found that both CysPAI-1 proteins significantly diminished the mean sprout area in a concentration-dependent fashion. The inhibitory effect present in the two examined endothelial cells systems of different origin and functional characteristics - human umbilical vein endothelial cells (HUVEC) and human lung microvascular endothelial cells (HLMVEC) cultures - was noticeably greater for HLMVEC -high urokinase-producers. Moreover, the inhibition rate was significantly greater for the ßT mutant than that for the hDßT PAI-1 mutant in all examined doses (P<0.002), proving a key role of anti-proteinase activity for this effect. Therefore, we concluded that PAI-1 apart from the total sprout length affects also sprouts area in the in vitro sprout formation angiogenesis assay. This effect was achieved mainly via PAI-1's anti-proteinase activity.

Słowa kluczowe

EN

endothelial cell; urokinase; blood vessel; in vitro; plasminogen activator inhibitor type-1; angiogenesis

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology. Supplement
• Rocznik: 2004
• Tom: 55
• Numer: 3
• Opis fizyczny: p.49-56,fig.,ref.

Twórcy

autor

Chorostowska-Wynimko J.

• National Istitute of Tuberculosis and Lung Diseases, 26 Plocka St., 01-138 Warsaw, Poland

autor

Skrzypczak-Jankun E.

autor

Jankun J.