© 2000 American Heart Association, Inc.
Integrative Physiology |
Plasminogen Is a Critical Determinant of Vascular Remodeling in Mice
From the Children’s Hospital Research Foundation, Cincinnati, Ohio (A.F.D., H.L.T., K.W.K., T.H.B., J.L.D.), and the Cardiovascular Division, Brigham and Women’s Hospital, Boston, Mass (D.I.S.).
Correspondence to Jay L. Degen, PhD, Division of Developmental Biology, Children’s Hospital Research Foundation, 3333 Burnet Ave, Cincinnati, OH 45229-3039. E-mail degenjl{at}chmcc.org
Abstract—Extracellular proteolysis is likely to be a feature of vascular remodeling associated with atherosclerotic and restenotic arteries. To investigate the role of plasminogen-mediated proteolysis in remodeling, polyethylene cuffs were placed around the femoral arteries of mice with single and combined deficiencies in plasminogen and fibrinogen. Neointimal development occurred in all mice and was unaffected by genotype. Significant compensatory medial remodeling occurred in the cuffed arteries of control mice but not in plasminogen-deficient mice. Furthermore, focal areas of medial atrophy were frequently observed in plasminogen-deficient mice but not in control animals. A simultaneous deficit of fibrinogen restored the potential of the arteries of plasminogen-deficient mice to enlarge in association with neointimal development but did not eliminate the focal medial atrophy. An intense inflammatory infiltrate occurred in the adventitia of cuffed arteries, which was associated with enhanced matrix deposition. Adventitial collagen deposition was apparent after 28 days in control and fibrinogen-deficient arteries but not in plasminogen-deficient arteries, which contained persistent fibrin. These studies demonstrate that plasmin(ogen) contributes to favorable arterial remodeling and adventitial collagen deposition via a mechanism that is related to fibrinogen, presumably fibrinolysis. In addition, these studies reveal a fibrin-independent role of plasminogen in preventing medial atrophy in challenged vessels. (Circ Res. 2000;87:133-139.)
Key Words: neointima • inflammation • plasminogen • fibrinogen • vascular remodeling
This article has been cited by other articles:
 |
|
 |
|
  W. P. Fay, N. Garg, and M. Sunkar Vascular Functions of the Plasminogen Activation System Arterioscler. Thromb. Vasc. Biol., June 1, 2007; 27(6): 1231 - 1237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Otsuka, A. Stempien-Otero, A. D. Frutkin, and D. A. Dichek Mechanisms of TGF-{beta}1-Induced Intimal Growth: Plasminogen-Independent Activities of Plasminogen Activator Inhibitor-1 and Heterogeneous Origin of Intimal Cells Circ. Res., May 11, 2007; 100(9): 1300 - 1307. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Kairuz, M. N. Barber, C. R. Anderson, M. Kanagasundaram, G. R. Drummond, and R. L. Woods C-type natriuretic peptide (CNP) suppresses plasminogen activator inhibitor-1 (PAI-1) in vivo Cardiovasc Res, June 1, 2005; 66(3): 574 - 582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kawai, K. Ando, A. Tojo, T. Shimosawa, K. Takahashi, M. L. Onozato, M. Yamasaki, T. Ogita, T. Nakaoka, and T. Fujita Endogenous Adrenomedullin Protects Against Vascular Response to Injury in Mice Circulation, March 9, 2004; 109(9): 1147 - 1153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Hattori, S. Mizuno, Y. Yoshida, K. Chin, M. Mishima, T. H. Sisson, R. H. Simon, T. Nakamura, and M. Miyake The Plasminogen Activation System Reduces Fibrosis in the Lung by a Hepatocyte Growth Factor-Dependent Mechanism Am. J. Pathol., March 1, 2004; 164(3): 1091 - 1098. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Kerlin, B. C. Cooley, B. H. Isermann, I. Hernandez, R. Sood, M. Zogg, S. B. Hendrickson, M. W. Mosesson, S. Lord, and H. Weiler Cause-effect relation between hyperfibrinogenemia and vascular disease Blood, March 1, 2004; 103(5): 1728 - 1734. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Razzaq, R. Bass, D. J. Vines, F. Werner, S. A. Whawell, and V. Ellis Functional Regulation of Tissue Plasminogen Activator on the Surface of Vascular Smooth Muscle Cells by the Type-II Transmembrane Protein p63 (CKAP4) J. Biol. Chem., October 24, 2003; 278(43): 42679 - 42685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. G. Bannach, A. Gutierrez, B. J. Fowler, T. H. Bugge, J. L. Degen, R. J. Parmer, and L. A. Miles Localization of Regulatory Elements Mediating Constitutive and Cytokine-stimulated Plasminogen Gene Expression J. Biol. Chem., October 4, 2002; 277(41): 38579 - 38588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. R. Pendurthi, M. Ngyuen, P. Andrade-Gordon, L. C. Petersen, and L. V. M. Rao Plasmin Induces Cyr61 Gene Expression in Fibroblasts Via Protease-Activated Receptor-1 and p44/42 Mitogen-Activated Protein Kinase-Dependent Signaling Pathway Arterioscler. Thromb. Vasc. Biol., September 1, 2002; 22(9): 1421 - 1426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kaneko, S. Fujii, A. Matsumoto, D. Goto, N. Ishimori, K. Watano, T. Furumoto, T. Sugawara, B. E. Sobel, and A. Kitabatake Induction of Plasminogen Activator Inhibitor-1 in Endothelial Cells by Basic Fibroblast Growth Factor and Its Modulation by Fibric Acid Arterioscler. Thromb. Vasc. Biol., May 1, 2002; 22(5): 855 - 860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Kenagy, J. W. Fischer, M. G. Davies, S. A. Berceli, S. M. Hawkins, T. N. Wight, and A. W. Clowes Increased Plasmin and Serine Proteinase Activity During Flow-Induced Intimal Atrophy in Baboon PTFE Grafts Arterioscler. Thromb. Vasc. Biol., March 1, 2002; 22(3): 400 - 404. [Abstract] [Full Text] [PDF]
|
|