Macrophages and platelets are the major source of protease nexin-1 in human atherosclerotic plaque.
OBJECTIVE
Protease nexin-1 (PN-1), a serpin constitutively expressed by vascular smooth muscle cells and endothelial cells, inhibits thrombin, plasminogen activators, and plasmin and can thus be expected to play a role in vascular biology. The present study addressed the question of PN-1 expression in human atherothrombosis.


RESULTS
Immunohistochemistry and biochemical studies confirmed that PN-1 was expressed at a moderate level in the medial layer of normal human arteries and showed that PN-1 expression was increased in atherothrombotic lesions. In early noncomplicated plaques, PN-1 was associated with infiltrating mononuclear cells. A strong PN-1 signal was observed in advanced lesions, principally in intraplaque hemorrhage-related structures. Monocytes/macrophages and platelets were identified as the main sources of PN-1 within atherothrombotic material. Isolated human monocytes and platelets both expressed high levels of active PN-1, and monocyte PN-1 expression was upregulated, at both messenger and protein levels, in response to stimulation by lipopolysaccharides. In contrast, PN-1 expression was downregulated during their differentiation into macrophages which were shown to produce degraded forms of PN-1.


CONCLUSIONS
Platelets and monocytes/macrophages are a major source of PN-1 in human atherothrombotic plaques. PN-1 could thus represent a new actor in the evolution of atherosclerotic lesions.
Mansilla
Silvana
S
INSERM, U698, Paris, France.
Boulaftali
Yacine
Y
Venisse
Laurence
L
Arocas
Véronique
V
Meilhac
Olivier
O
Michel
Jean-Baptiste
JB
Jandrot-Perrus
Martine
M
Bouton
Marie-Christine
MC
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002454:Cell Differentiation; D002478:Cells, Cultured; D016894:Endarterectomy, Carotid; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D058255:Protease Nexins; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D058258:Serpin E2; D015854:Up-Regulation
D016564:Amyloid beta-Protein Precursor; D017395:Plasminogen Activator Inhibitor 1; D058255:Protease Nexins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C051321:SERPINE1 protein, human; C545486:SERPINE2 protein, human; D058258:Serpin E2