Az érfal trombogenitása és annak szabályozása = Vessel wall thrombogenicity and its regulation

Fiziologias hemosztazis ill. arterias trombozis keletkezesekor a trombocitak a gyorsan aramlo verből von Willebrand faktoron keresztul tapadnak ki az erfalban levő kollagenhez. Az erfal matrix komponenseit vizsgalva megallapitottuk, hogy a media retegből izolalhato proteoglikanok, a perlecan es a biglycan/decorin gatoljak a von Willebrand faktor kotődeset a kollagenhez, es igy a jelenletukben in vitro kialakulo kollagen struktura antitrombogen. Az adventitia proteoglikanok a kollagen trombogenitasat nem befolyasoljak. A media proteoglikanok antitrombotikus tulajdonsaga perlecan eseteben a feherje komponenshez, mig biglycan, decorin eseteben az adventitia retegetől elterő kondroitin szulfat/dermatan szulfat oldallancokhoz kothető. Kimutattuk, hogy plazmin, trombin, es neutrofil granulocita metalloproteinazok fokozzak az erfal media retegeben levő kollagen trombogenitasat, ami gyulladasban ill. hemosztazisban fokozott trombozishajlamhoz vezethet. Az arterias trombusban a trombocitak egymashoz fibrinogenen, von Willebrand faktoron keresztul kapcsolodnak. Megallapitottuk, hogy fiziologias koncentracio viszonyok eseten a von Willebrand faktor vedi a fibrinogent a plazmin hasitasa ellen, es bar ő is plazmin szubsztrat, a hatas nem a szubsztratok kompeticiojan alapul. Arterias trombusban a fibrinogen kb. 50 %-a fibrinne alakul, ennek degradaciojat a von Willebrand faktor nem befolyasolja. | In the course of hemostasis or arterial thrombosis platelets are captured from rapidly flowing blood by von Willebrand factor immobilized on vascular collagens. Collagen structures in the media layer of vessel wall, however, do not support platelet adhesion. We have found that perlecan and biglycan/decorin isolated from the media layer of the arterial wall, but none of the adventitia proteoglycans, inhibit von Willebrand factor binding to collagen and platelet adhesion to reconstituted collagen surfaces. The antithrombotic effect of perlecan is due to its core protein component, whereas the inhibitory effects of media biglycan and decorin are attributable to their chondroitin sulphate/dermatan sulphate chains, which are different from those in adventitia biglycan and decorin. We have shown that the antithrombotic properties of the media collagen structures, in situ, can be disrupted by plasmin, thrombin and matrix metalloproteases of neutrophil granulocytes, which suggests that vascular thrombogenicity may increase at sites of inflammation and when the hemostatic system is activated. In platelet-rich thrombi fibrinogen and von Willebrand factor serve as molecular bridges between platelets. Our data indicate that von Willebrand factor protects fibrinogen, but not fibrin from plasmin degradation. Although von Willebrand factor is also a substrate for plasmin, its protective effect is not due to substrate competition.