Overexpression of urokinase receptor and cell surface urokinase-type plasminogen activator in the human vessel wall with different types of atherosclerotic lesions.
Urokinase-type plasminogen activator (UPA) has been implicated in a broad spectrum of pathogenic processes involved in the formation and disruption of atherosclerotic lesions. Up to now, there is no consensus on the contribution of membrane-bound UPA and its receptor CD87 (UPAR) to the development of atherosclerosis. In this study, we determined comparatively the levels of UPAR and UPAR-bound UPA in segments of human coronary and aortic vessels with different degrees of atherosclerotic lesions (macroscopically normal areas, early atherosclerotic lesions, fibrous and calcified plaques). The UPAR content increased progressively with the severity of atherosclerosis. In aortic segments, in which intima and media layers were analyzed separately, the content of UPAR in the intima significantly exceeded the levels measured in the media. Using a detergent-phase separation method with a Triton X-114-containing buffer, we could demonstrate that the levels of membrane (glycosylphosphatidylinositol)-anchored UPAR were significantly higher in the intima of early atherosclerotic lesions as well as in the cap areas of fibrous plaques compared with macroscopically normal areas. However, only 20-25% of the intimal and 30-50% of the medial glycosylphosphatidylinositol-UPAR was occupied by UPA as determined on a molar basis. These data confirm that the overexpression of UPAR in advanced atherosclerotic lesions contributes to lesion development. Whether UPAR's excess over cell surface UPA provides an additional role for this receptor in atherogenesis besides UPA-mediated proteolysis remains to be elucidated.
Steins
Martin B
MB
Department of Medicine/Hematology and Oncology, University of Muenster, Germany. steinsm@mednet.uni-muenster.de
Padró
Teresa
T
Schwaenen
Carsten
C
Ruiz
Sandra
S
Mesters
Rolf M
RM
Berdel
Wolfgang E
WE
Kienast
Joachim
J
D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D055293:Receptors, Urokinase Plasminogen Activator; D017539:Tunica Intima / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator