411 J.X.-J. Yuan et al. (eds.), Textbook of Pulmonary Vascular Disease,
DOI 10.1007/978-0-387-87429-6_27, © Springer Science+Business Media, LLC 2011
Abstract In this chapter, we use the term “plasminogen
system” to designate the pathway that controls the
conversion of plasminogen to plasmin and the proximal
consequences of plasminogen activation. The “plasmino-
gen system” is synonymous with the “fibrinolytic system,”
a nomenclature that emphasizes the primary substrate of
plasmin, fibrin, and function, and the outcome of fibrin
degradation, fibrinolysis. However, evidence documents
vital roles of components of the plasminogen system in
physiological and pathological processes which cannot
be attributed to and clearly extend beyond its role in clot
dissolution. In particular, components of the plasminogen
system can influence cell invasion into tissue, which is
dependent on the capacity of plasmin to degrade various
extracellular matrix (ECM) proteins, including fibronectins,
thrombospondins, von Willebrand factor, and laminin, and
to activate certain matrix metalloproteases, enzymes that
degrade still other ECM constituents. Many components of
the plasminogen system also interact with cells to generate
intracellular signals that affect cell survival, proliferation,
adhesion, and migration. Some of these roles are directly
relevant to endothelial cell (EC) and smooth muscle cell
(SMC) biology and it is in this context that we consider the
interaction of the plasminogen system with these vascular
cells. Why should a book that focuses on pulmonary vas-
cular disease have a chapter dedicated to the interaction of
the plasminogen system with the vessel wall? The answer
is straightforward; there is compelling evidence linking the
plasminogen system to pathological processes in the lung.
Keywords Fibrinolysis • Thrombosis • Cell adhesion
•Migration•Endothelialcell•Smoothmusclecell•Fibrin
•Fibronectin•Plasmin
1 Introduction
In this chapter, we use the term “plasminogen system” to
designate the pathway that controls the conversion of plasmi-
nogen to plasmin and the proximal consequences of plasmi-
nogen activation. The “plasminogen system” is synonymous
with the “fibrinolytic system,” a nomenclature that empha-
sizes the primary substrate of plasmin, fibrin, and function,
and the outcome of fibrin degradation, fibrinolysis. However,
evidence from enumerable in vitro studies and numerous
studies conducted in mice deficient in various components
documents vital roles of components of the plasminogen
system in physiological and pathological processes which
cannot be attributed to and clearly extend beyond its role in
clot dissolution. In particular, components of the plasmino-
gen system can influence cell invasion into tissue, which is
dependent on the capacity of plasmin to degrade various
extracellular matrix (ECM) proteins, including fibronectins,
thrombospondins, von Willebrand factor, and laminin, and to
activate certain matrix metalloproteases, enzymes that
degrade still other ECM constituents. Many components of
the plasminogen system also interact with cells to generate
intracellular signals that affect cell survival, proliferation,
adhesion, and migration. Some of these roles are directly rel-
evant to endothelial cell (EC) and smooth muscle cell (SMC)
biology and it is in this context that we consider the interac-
tion of the plasminogen system with these vascular cells.
Why should a book that focuses on pulmonary physiol-
ogy have a chapter dedicated to the interaction of the plas-
minogen system with the vessel wall? The answer is
straightforward; there is compelling evidence linking the
plasminogen system to pathological processes in the lung.
In bleomycin-induced pulmonary fibrosis, deficiencies of
plasminogen,urokinaseplasminogenactivator (uPA),uPA
receptor(u-PAR),andtissueplasminogenactivator(tPA)in
mice, all components of the plasminogen system, alter the
pathogenic response substantially [1, 2]. Similarly, the
response to lung infections and endotoxin-induced lung
injury is markedly altered in mice deficient in certain com-
ponents of the plasminogen system, and expression patterns
R.Das(*)
Department of Molecular Cardiology, Cleveland Clinic Foundation,
9500EuclidAvenueNB-50,Cleveland,OH44195,USA
e-mail: dasr@ccf.org
Chapter 27
Interaction of the Plasminogen System with the Vessel Wall
Riku Das and Edward F. Plow