Separation of the arterial wall from blood contact using hydrogel barriers reduces intimal thickening after balloon injury in the rat: the roles of medial and luminal factors in arterial healing.

The objective of this study was to clarify the relative roles of medial versus luminal factors in the induction of thickening of the arterial intima after balloon angioplasty injury. Platelet-derived growth factor (PDGF) and thrombin, both associated with thrombosis, and basic fibroblast growth factor (bFGF), stored in the arterial wall, have been implicated in this process. To unequivocally isolate the media from luminally derived factors, we used a 20-microns thick hydrogel barrier that adhered firmly to the arterial wall to block thrombus deposition after balloon-induced injury of the carotid artery of the rat. Thrombosis, bFGF mobilization, medial repopulation, and intimal thickening were measured. Blockade of postinjury arterial contact with blood prevented thrombosis and dramatically inhibited both intimal thickening and endogenous bFGF mobilization. By blocking blood contact on the two time scales of thrombosis and of intimal thickening, and by using local protein release to probe, by reconstitution, the individual roles of PDGF-BB and thrombin, we were able to conclude that a luminally derived factor other than PDGF or thrombin is required for the initiation of cellular events leading to intimal thickening after balloon injury in the rat. We further conclude that a luminally derived factor is required for mobilization of medial bFGF.

[1]  M. Reidy,et al.  Role of basic fibroblast growth factor in vascular lesion formation. , 1991, Circulation research.

[2]  Jeffrey A. Hubbell,et al.  Photopolymerized hydrogel materials for drug delivery applications , 1995 .

[3]  D. Rifkin,et al.  Release of basic fibroblast growth factor-heparan sulfate complexes from endothelial cells by plasminogen activator-mediated proteolytic activity. , 1990 .

[4]  W. Roberts,et al.  Effectiveness of Recombinant Desulphatohirudin in Reducing Restenosis After Balloon Angioplasty of Atherosclerotic Femoral Arteries in Rabbits , 1991, Circulation.

[5]  J. Folkman,et al.  Basic fibroblast growth factor binds to subendothelial extracellular matrix and is released by heparitinase and heparin-like molecules. , 1989, Biochemistry.

[6]  T. Nikkari,et al.  Induction of 15-lipoxygenase mRNA and protein in early atherosclerotic lesions. , 1995, Circulation.

[7]  E. Edelman,et al.  Basic fibroblast growth factor enhances the coupling of intimal hyperplasia and proliferation of vasa vasorum in injured rat arteries. , 1992, The Journal of clinical investigation.

[8]  M. Rusnati,et al.  Basic fibroblast growth factor is released from endothelial extracellular matrix in a biologically active form , 1989, Journal of cellular physiology.

[9]  J. Hubbell,et al.  Local thrombin synthesis and fibrin formation in an in vitro thrombosis model result in platelet recruitment and thrombus stabilization on collagen in heparinized blood. , 1990, The Journal of laboratory and clinical medicine.

[10]  R. Friedman,et al.  The effect of thrombocytopenia on experimental arteriosclerotic lesion formation in rabbits. Smooth muscle cell proliferation and re-endothelialization. , 1977, The Journal of clinical investigation.

[11]  E. Nabel,et al.  Recombinant platelet-derived growth factor B gene expression in porcine arteries induce intimal hyperplasia in vivo. , 1993, The Journal of clinical investigation.

[12]  A. Eldor,et al.  Heparanase activity expressed by platelets, neutrophils, and lymphoma cells releases active fibroblast growth factor from extracellular matrix. , 1990, Cell regulation.

[13]  T. Maciag,et al.  The heparin-binding (fibroblast) growth factor family of proteins. , 1989, Annual review of biochemistry.

[14]  C. A. de la Motte,et al.  Thrombin receptor-activating peptides differentially stimulate platelet-derived growth factor production, monocytic cell adhesion, and E-selectin expression in human umbilical vein endothelial cells. , 1994, The Journal of biological chemistry.

[15]  P. Dicorleto,et al.  Stable expression of human platelet-derived growth factor B chain by bovine aortic endothelial cells. Matrix association and selective proteolytic cleavage by thrombin. , 1994, The Journal of biological chemistry.

[16]  S. Schwartz,et al.  Platelet-derived growth factor promotes smooth muscle migration and intimal thickening in a rat model of balloon angioplasty. , 1992, The Journal of clinical investigation.

[17]  S. Coughlin,et al.  Thrombin stimulates proliferation of cultured rat aortic smooth muscle cells by a proteolytically activated receptor. , 1993, The Journal of clinical investigation.

[18]  E. Nabel,et al.  Recombinant fibroblast growth factor-1 promotes intimal hyperplasia and angiogenesis in arteries in vivo , 1993, Nature.

[19]  Jeffrey A. Hubbell,et al.  Rapid photopolymerization of immunoprotective gels in contact with cells and tissue , 1992 .

[20]  M. Reidy,et al.  Kinetics of cellular proliferation after arterial injury. V. Role of acute distension in the induction of smooth muscle proliferation. , 1989, Laboratory investigation; a journal of technical methods and pathology.

[21]  J. Hubbell,et al.  Inhibition of thrombosis and intimal thickening by in situ photopolymerization of thin hydrogel barriers. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[22]  M. Klagsbrun,et al.  Sequestration and Release of Basic Fibroblast Growth Factor a , 1991, Annals of the New York Academy of Sciences.

[23]  N. Olson,et al.  Intimal smooth muscle cell proliferation after balloon catheter injury. The role of basic fibroblast growth factor. , 1992, The American journal of pathology.

[24]  R. Ross,et al.  The biology of platelet-derived growth factor , 1986, Cell.

[25]  V. Fuster,et al.  Syndromes of accelerated atherosclerosis: role of vascular injury and smooth muscle cell proliferation. , 1990, Journal of the American College of Cardiology.

[26]  M. Reidy,et al.  Inhibition of neointimal smooth muscle accumulation after angioplasty by an antibody to PDGF , 1991, Science.

[27]  V. Fuster,et al.  The role of platelets, thrombin and hyperplasia in restenosis after coronary angioplasty. , 1991, Journal of the American College of Cardiology.

[28]  E J Topol,et al.  The restenosis paradigm revisited: an alternative proposal for cellular mechanisms. , 1992, Journal of the American College of Cardiology.

[29]  M. Benezra,et al.  Thrombin enhances degradation of heparan sulfate in the extracellular matrix by tumor cell heparanase. , 1992, Experimental cell research.