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PubMed1997

Limited proteolysis of angiogenin by elastase is regulated by plasminogen.

Human neutrophil elastase cleaves angiogenin at the Ile-29/Met-30 peptide bond to produce two major disulfide-linked fragments with apparent molecular weights of 10,000 and 4000, respectively. Elastase-cleaved angiogenin has slightly increased ribonucleolytic activity, but has lost its ability to undergo nuclear translocation in endothelial cells, a process essential for angiogenic activity. Cleavage appears to alter the cell-binding properties of angiogenin, despite the fact that it occurs some distance from the putative receptor-binding site, since the elastase-cleaved protein fails to compete with its native counterpart for nuclear translocation in endothelial cells. Plasminogen specifically accelerates elastase proteolysis of angiogenin. It does not enhance elastase activity toward ribonuclease A or the synthetic peptide substrate MeOSuc-Ala-Ala-Pro-Val-pNA. Plasminogen-accelerated inactivation of angiogenin by elastase might be a significant event in the process of angiogenin-induced angiogenesis since (i) angiogenin and plasminogen circulate in plasma at high concentrations, (ii) angiogenin, especially when bound to actin, activates tissue plasminogen activator to generate plasmin from plasminogen, and (iii) elastase cleaves plasminogen to produce angiostatin, a potent inhibitor of angiogenesis and metastasis. Interrelationships among angiogenin, plasminogen, plasminogen activators, elastase, and angiostatin may provide a sensitive regulatory system to balance angiogenesis and antiangiogenesis.

Amino Acid Sequence↗
PubMed1988

Analysis of the plasminogen activator activity of the human glomerulus.

An assay was developed to measure plasminogen activator activity from isolated human glomeruli. Activator was extracted from individual glomeruli with 0.2 M phosphate-buffered saline, pH 7.4 (PBS), containing 0.01% Triton X-100 and quantitated in 125I-fibrin films. Quenching studies using antibodies to tissue plasminogen activator and urokinase revealed that the extracted glomerular plasminogen activator activity contained both tissue plasminogen activator of urokinase. Monoclonal and polyclonal antibodies raised to tissue plasminogen activator demonstrated low-level inhibition of urokinase activity and monoclonal and polyclonal antibodies to urokinase demonstrated low-level inhibition of tissue plasminogen activator activity. The assay should be applicable to the study of glomerular plasminogen activator activity in experimental and human kidney diseases. The detection of antibody cross-reactivity to tissue plasminogen activator and urokinase may be related to the sensitivity of the 125I-fibrin assay and to the structural similarities of these activators.

Humans↗
PubMed1996

Induction of urokinase-type plasminogen activator in rat facial nucleus by axotomy of the facial nerve.

The response of plasminogen activator activity in the CNS to peripheral nerve axotomy was examined in vivo. After transection of the rat facial nerve, a transient increase in plasminogen activator activity was observed in the facial nucleus on the operated side with maximal activity 3-5 days after lesion. This activity was inhibited by the urokinase-specific inhibitor amiloride but not by antibodies against tissue plasminogen activator. The molecular mass of the induced form of plasminogen activator was estimated to be approximately 48 kDa. An in vitro assay of plasminogen hydrolysis also demonstrated an increase in amiloride-sensitive plasminogen activator activity in facial nerve extracts following facial nerve axotomy. These data indicate that the plasminogen activator activity induced in the facial nucleus following axotomy of facial motoneurons is of the urokinase type. It is suggested that the urokinase-type plasminogen activator might play a role in the events accompanying injury and regeneration in the facial nucleus following motoneuron lesion.

Animals↗
PubMed2001

Plasminogen expression in the neonatal and adult mouse brain.

Tissue-type plasminogen activator (tPA) has been implicated in a variety of types of neural plasticity, including cell migration, occlusion-induced visual system plasticity, and learning. In the periphery, plasminogen serves as tPA's primary substrate; however, studies attempting to identify plasminogen in the central nervous system have produced mixed results. We have performed a comprehensive, multitechnique study examining plasminogen expression in the neonatal and adult mouse brain. Reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization reveal plasminogen mRNA in the cortex, hippocampus and cerebellum of both neonatal and adult C57BL/6 mice. Immunocytochemistry reveals plasminogen protein expression in these same brain regions. Notably, plasminogen expression in the cerebellum occurs in the granule cell and the Purkinje cell layers. tPA activity in these same regions is involved in granule cell migration during development and motor learning in adulthood. Therefore, these findings demonstrate that plasminogen is present in the central nervous system and localized to areas where it could serve as a substrate for plasticity-related increases in tPA activity.

Animals↗
PubMed1980

Production and release of plasminogen by isolated perfused rat liver.

In view of conflicting evidence for a major hepatic role in the synthesis of circulating plasminogen, the precursor of the fibrinolytic enzyme plasmin, we carried out the present study with a sensitive assay in order to measure the accumulation of small quantities of plasminogen in a recycling rat liver perfusion system. We have purified plasminogen from Sprague-Dawley rat plasma and have raised a monospecific antiserum against it in rabbits. Isolated rat liver perfusions were performed with an oxygenated recycling perfusate consisting of a perfluorotributylamine/Pluronic F-68 emulsion (Fluosol 43) free of plasma proteins and blood cells. The system was shown to be capable of synthesizing albumin and transferrin. The cumulative appearance of plasminogen in the perfusate was measured by a sensitive, specific radioimmunoassay. Plasminogen concentration increased progressively during the first 2 hr of perfusion; the observed average net synthesis in five separate experiments was approximately 35 microgram/hr per 100 g of body weight. Exposure of the perfused liver to 18 microM cycloheximide inhibited additional increase in the titer of plasminogen. Evidence for de novo synthesis was provided by the incorporation of 14C-labeled leucine into specific immunoprecipitates of plasminogen and the inhibition of this incorporation by cycloheximide. Analysis of the immunoprecipitates by sodium dodecyl sulfate/polyacrylamide gel electrophoresis revealed a single peak of radioactivity corresponding to Mr of 82,000. These data indicate that the liver is a major site of plasminogen production.

Animals↗
PubMed1997

The mechanism of cancer-mediated conversion of plasminogen to the angiogenesis inhibitor angiostatin.

Angiostatin, a potent naturally occurring inhibitor of angiogenesis and growth of tumor metastases, is generated by cancer-mediated proteolysis of plasminogen. Human prostate carcinoma cells (PC-3) release enzymatic activity that converts plasminogen to angiostatin. We have now identified two components released by PC-3 cells, urokinase (uPA) and free sulfhydryl donors (FSDs), that are sufficient for angiostatin generation. Furthermore, in a defined cell-free system, plasminogen activators [uPA, tissue-type plasminogen activator (tPA), or streptokinase], in combination with one of a series of FSDs (N-acetyl-L-cysteine, D-penicillamine, captopril, L-cysteine, or reduced glutathione] generate angiostatin from plasminogen. An essential role of plasmin catalytic activity for angiostatin generation was identified by using recombinant mutant plasminogens as substrates. The wild-type recombinant plasminogen was converted to angiostatin in the setting of uPA/FSD; however, a plasminogen activation site mutant and a catalytically inactive mutant failed to generate angiostatin. Cell-free derived angiostatin inhibited angiogenesis in vitro and in vivo and suppressed the growth of Lewis lung carcinoma metastases. These findings define a direct mechanism for cancer-cell-mediated angiostatin generation and permit large-scale production of bioactive angiostatin for investigation and potential therapeutic application.

Angiostatins↗
PubMed1996

Autoproteolysis or plasmin-mediated cleavage of factor Xaalpha exposes a plasminogen binding site and inhibits coagulation.

Blood coagulation factor Xa (FXa) has recently been shown to function as a plasminogen receptor in the presence of procoagulant phospholipid (phosphatidylserine; PS) and Ca2+. In the current work, the possible effect of autoproteolytic and plasmin-mediated cleavage of FXa on complex formation with plasminogen was investigated. 125I-plasminogen binding to derivatives of FXa electrotransferred to polyvinylidene difluoride revealed that the autoproteolytic conversion of FXaalpha to FXabeta was required for the expression of a plasminogen binding site. In the presence of PS and Ca2+, plasmin was shown to convert FXaalpha to a FXabeta-like species at least 3 orders of magnitude faster than the autoproteolytic mechanism. This also resulted in the exposure of a plasminogen binding site. Further processing by plasmin generated a fragment (33 kDa) due to cleavage at Gly331 in the FXa heavy chain. Production of this species enhanced apparent plasminogen binding compared with FXabeta and resulted in the loss of FXa amidolytic and clotting activity. In the absence of either PS or Ca2+, the plasmin-mediated fragmentation of FXaalpha was altered to include a FXabeta-like molecule and a species (40 kDa) with intact beta-heavy chain disulfide linked to a COOH-terminal fragment of the light chain starting at Tyr44. Neither of these products was observed to interact with plasminogen. The 40-kDa species had amidolytic activity comparable with FXaalpha but inhibited clotting activity. Cumulatively the data provide the first evidence for a functional difference between the FXa subforms and suggest a mechanism where autoproteolysis and plasmin-mediated cleavage modulate the function of FXaalpha from a procoagulant enzyme to a profibrinolytic plasminogen receptor.

Amino Acid Sequence↗
PubMed1997

Evidence for a novel O-linked sialylated trisaccharide on Ser-248 of human plasminogen 2.

Human plasminogen, the inactive precursor of plasmin, exists in two major glycoforms. Plasminogen 1 contains an N-linked oligosaccharide at Asn-289 and an O-linked oligosaccharide at Thr-345. Plasminogen 2 is known to contain only an O-linked oligosaccharide at Thr-345. However, plasminogen 2 displays a further well documented microheterogeneity dependent on the N-acetylneuraminic acid content, which has functional consequences with regard to activation of plasminogen. The proposed structure and number of known oligosaccharide linkages in plasminogen 2 is insufficient to account for this microheterogeneity. In the present study, a combination of trypsin digestion, lectin affinity chromatography, Edman degradation amino acid sequence analysis, carbohydrate composition analysis, and mass spectrometry revealed the existence of a novel site for O-linked glycosylation on plasminogen 2 at Ser-248. Direct evidence for the structure of the carbohydrate was obtained from a combination of lectin affinity chromatography, desialylation experiments, and mass spectrometry analysis. These findings provide a structural basis for some of the observed microheterogeneity, and have implications with regard to the known functional consequences of the extent of sialylation of plasminogen.

Amino Acid Sequence↗
PubMed2002

Localization of regulatory elements mediating constitutive and cytokine-stimulated plasminogen gene expression.

The activity of plasmin, the major enzyme responsible for dissolving fibrin clots, is regulated by plasminogen activators, plasminogen activator inhibitors, alpha(2)-antiplasmin, and inflammatory mediators. Recent studies suggest that plasmin activity can be regulated also at the level of plasminogen gene expression. In this study, we characterized the murine plasminogen promoter and 5'-flanking region. The major transcription start site was identified at -83 bp relative to the ATG translational initiation codon. A series of 5'-flanking sequences up to 2400 bp upstream of the transcription initiation site were fused to the luciferase reporter gene and transfected into hepatocytic cells. A 106-bp 5'-flanking region of the murine plasminogen gene demonstrated sufficient functional promoter activity in plasminogen-expressing cells. IL-6 treatment stimulated luciferase activity driven by the 5'-flanking region and an intact consensus IL-6-responsive element at -791, was required for maximal stimulation by this cytokine. These results indicate the presence of regulatory elements in the 5'-flanking region of the murine plasminogen promoter that may regulate murine plasminogen gene expression and, hence, plasmin activity.

Amino Acid Motifs↗
PubMed1974

Induction of macrophage plasminogen activator by endotoxin stimulation and phagocytosis: evidence for a two-stage process.

The injection of thioglycollate medium into the peritoneal cavity of the mouse induces high levels of macrophage fibrinolytic activity due to the production and secretion of a plasminogen activator, a trypsinlike serine protease, which is absent in unstimulated macrophages. Intraperitoneal injection of endotoxin or mineral oil can stimulate only a fraction (<10%) of the fibrinolytic activity of thioglycollate cells, similar to the partial stimulation (<10%) seen 1-2 days after phagocytosis of latex or SRBC by unstimulated macrophages. The endotoxin-stimulated macrophages contain and release relatively low levels of plasminogen activator, but these primed cells can be triggered to produce and secrete high levels of enzyme, by phagocytosis of latex. Under conditions where the plasminogen activator is induced and secreted, there are no effects on the production and/or release of lysozyme or intracellular acid hydrolases, Discovery of a two-stage procedure for inducing macrophage plasminogen activator made it possible to study the role of cell priming and phagocytosis separately. Endotoxin was a more effective priming agent, weight for weight, than lipid A:BSA complex. Secretion of the plasminogen activator was induced only by thioglycollate, or endotoxin and latex. In situ fibrinolysis was induced by these agents and mineral oil, BCG, and fetal calf serum, in decreasing order of effectiveness. Phagocytosis of latex in all cases except thioglycollate stimulation, increased fibrinolytic activity from three- to sixfold. Latex and a variety of other particles such as M. lysodeikticus, aggregated gamma-globulin and immune complexes showed dose-dependent stimulation of fibrinolysis by endotoxin-primed macrophages. Although the initial phagocytic trigger was not specific for the substance employed, the ability to induce a sustained response depended on the persistence of the phagocytized particle within the cell. Fibrinolysis and secretion of plasminogen activator continued at high levels for at least 9 days after uptake of latex, a nondigestible particle, whereas plasminogen activator was secreted only transiently after ingestion of rapidly digested M. lysodeikticus. The induction of plasminogen activator secretion provides a mechanism by which the activated macrophage can exert a selective effect on its extracellular environment.

Animals↗
PubMed2003

A K19E missense mutation in the plasminogen gene is a common cause of familial hypoplasminogenaemia.

The prevalence of familial plasminogen deficiency in Scotland has recently been calculated at 2.9/1000. However, little is known of the molecular genetic background and the frequency of plasminogen gene mutations in most cases of inherited plasminogen deficiency. Having previously identified 28 unrelated subjects with familial plasminogen deficiency from a cohort of 9611 blood donors, we have now reviewed 19 of these 28 subjects and screened the plasminogen gene in 15 subjects with hypoplasminogenaemia (plus five relatives) and four subjects with dysplasminogenaemia for mutations and polymorphisms. A missense mutation K19E in the plasminogen gene was found in 13 of the 15 propositi with hypoplasminogenaemia, in one of these in a homozygous manner. In two subjects with hypoplasminogenaemia, two new mutations (P353A and R471X) were identified. These three different mutations, if inherited in a homozygous or compound-heterozygous manner, may be associated with the development of ligneous conjunctivitis. In four subjects with dysplasminogenaemia, three heterozygous mutations (C548G, n = 1; A601T, n = 1; G693R, n = 2) were found. None of the propositi with plasminogen deficiency developed venous thrombosis at any time. In conclusion, the K19E mutation in the plasminogen gene is a common cause of hypoplasminogenaemia in Scotland, with an estimated prevalence of around 0.14%.

Amino Acid Sequence↗
PubMed1997

Recombinant tissue plasminogen activator restores perfusion in meningococcal purpura fulminans.

OBJECTIVE: To investigate whether an infusion of recombinant tissue plasminogen activator would dissolve microvascular thromboses and improve organ perfusion in a patient with fulminant meningococcemia. DESIGN: Descriptive case report. SETTING: Fifteen-bed pediatric intensive care unit (ICU) in a university hospital. PATIENT: A 4-month-old male with fulminant meningococcemia, refractory shock, and multiple organ failure. INTERVENTIONS: In addition to standard aggressive ICU care, the patient received a recombinant tissue plasminogen activator infusion at a total dose of 1.25 mg/kg over 4 hrs. MEASUREMENTS AND MAIN RESULTS: Heart rate, arterial blood pressure, urine output, and base deficit (as a reflection of severity of metabolic acidosis) were recorded immediately before the recombinant tissue plasminogen activator infusion and 4 hrs later, after completion of the recombinant tissue plasminogen activator infusion. The amount of exogenous vasopressor and inotropic support required to maintain the patient's hemodynamic status before and after recombinant tissue plasminogen activator infusion were also compared. Subjective observations regarding the patient's peripheral perfusion status were also noted. The patient showed a dramatic improvement in hemodynamics, urine output, and metabolic acidosis, as well as a perceived increase in skin perfusion after recombinant tissue plasminogen activator infusion. CONCLUSIONS: In this patient, recombinant tissue plasminogen activator infusion resulted in improved organ perfusion and cardiac performance. Selective use of recombinant tissue plasminogen activator in the treatment of fulminant meningococcemia merits further investigation.

Blood Circulation↗
PubMed2004

The effects of the plasminogen pathway on scar tissue formation.

OBJECTIVES/HYPOTHESIS: The authors sought to determine the role of the plasminogen pathway in wound healing. They hypothesized that decreased fibrin degradation may lead to increased collagen deposition. Presuming that the degree of histopathological abnormality correlates with the aesthetic appearance of the scar, we conducted a study that attempted to determine the histopathological appearance of scar tissue in mice with and without impaired function of the plasminogen pathway. STUDY DESIGN: Mice with and without deficiencies in the plasminogen pathway underwent surgery. The role of the plasminogen pathway in wound healing was studied by analysis of scar tissue formation using the methods described. METHODS: A 2-cm incision was made on the dorsum of mice with and without specified genetic deficiencies in the plasminogen pathway. After the animals were killed, the tissue was harvested, fixed, and prepared using hematoxylin and eosin as well as trichrome stains. Histopathological analysis and scoring were performed by two separate investigators in a blinded manner. Student's t test was used to determine statistical significance between groups. RESULTS: A statistically significant difference in collagen orientation was noted between mice with impaired plasminogen pathway function and the wild-type (control) group (P =.0163). A statistical trend toward improved wound healing for plasminogen-deficient mice was found for overall histomorphological score (P =.0706). CONCLUSION: The role of the plasminogen pathway in wound healing is one that should be noted and may lead to the development of new therapies that reduce scar tissue formation. Hence, the role of other thrombolytic and anti-thrombolytic agents in wound healing should be further investigated to precisely identify agents that play the most significant role in scar tissue formation.

Animals↗
PubMed2004

Plasminogen interaction and activation on Streptococcus mutans surface.

A number of pathogenic microorganisms have been previously shown to bind plasminogen. The subsequent activation of plasminogen into plasmin can contribute to their virulence. In this study, we have shown that Streptococcus mutans is able to bind both human plasminogen and plasmin. Binding of plasminogen to S. mutans was inhibited by L-lysine and epsilon-aminocaproic acid, indicating that binding is mediated via lysine-binding sites of plasminogen. S. mutans enhanced the activation of plasminogen by tissue plasminogen activator but not by urokinase. This enhancement turned out to be dependent on cell concentration. Zymogram analysis showed that the plasmin activity acquired after plasminogen binding and activation is the most important proteolytic activity in the strain tested. These results suggest a mechanism involving acquisition of a host protease that might contribute to the infective process of this microorganism.

Aminocaproates↗
PubMed2004

Interleukin-6-induced plasminogen gene expression in murine hepatocytes is mediated by transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta).

An emerging area of research has demonstrated that plasminogen functions in the acute-phase response to tissue injury, neoplastic growth or infection. We have previously shown that the acute-phase mediator, interleukin (IL)-6, increases circulating plasminogen levels via upregulation of plasminogen promoter activity. We also identified a putative IL-6 responsive element (nt -791 to -783; IL6-RE) in the plasminogen gene that is required for maximal stimulation of promoter activity by IL-6. For the present study, we investigated the transcription factors and signaling pathway mediating the response of the plasminogen gene to IL-6. In electrophoretic mobility shift assays (EMSAs), a radiolabeled oligonucleotide IL6-RE probe formed specific complexes with nuclear proteins from untreated hepatocytic cells. The extent of complex formation was markedly increased using nuclear proteins from IL-6-treated cells. Complex formation was abolished by an oligonucleotide with the consensus CCAAT/enhancer binding protein (C/EBP) sequence. Furthermore, complexes were supershifted by antibodies to C/EBPbeta. Treatment of Hepa 1-6 cells with the mitogen-activated protein kinase (MAPK) inhibitor, PD-98059, inhibited IL-6-stimulated plasminogen promoter activity. These results suggest that transcription factor C/EBPbeta and the MAPK pathway play key roles in the response of the plasminogen gene to IL-6, thus elucidating a major mechanism by which the plasminogen system is upregulated to perform its crucial functions in the acute-phase response.

Acute-Phase Reaction↗
PubMed1999

Human homozygous type I plasminogen deficiency and ligneous conjunctivitis.

On the basis of a questionnaire sent to the ophthalmology departments of hospitals throughout Germany, 10 patients with ligneous conjunctivitis or pseudomembranous disease, ranging in age from 1 to 71 years were identified. All 10 patients had severely reduced plasminogen levels. Genetic analysis revealed homozygous type I plasminogen deficiency (which had not previously been described in humans) in 7 patients and compound heterozygous plasminogen deficiency in 1 patient. Clear differentiation was not possible in 2 patients. Most of the parents had heterozygous plasminogen deficiency. None of the patients had experienced any episodes of thrombosis. Additionally, the following observations were made: 1) Levels of polymorphonuclear (PMN)-elastase protein were markedly elevated in 6 of 6 patients and 10 of 11 parents tested, and levels were higher in homozygotes than in heterozygotes. 2) Hereditary factor XII deficiency was found in 3 of 6 patients tested. 3) C1-inhibitor was elevated in 2 of 4 patients, prekallikrein was elevated in 1 of 4 patients, and plasminogen activator inhibitor type 1 was elevated in 1 of 4 patients. Infusions of lys-plasminogen concentrate induced pronounced fibrinolytic activity as indicated by high levels of D-dimer, increases in plasmin-antiplasmin complex and decreases in polymorphonuclear elastase. C1-inhibitor, prekallikrein and PAI-1 normalized after repeated infusions of lys-plasminogen. In contrast to dysplasminogenemia, severe type I plasminogen deficiency might be seen as a problem of extravascular space, in particular of the mucous membranes, possibly triggered by mechanically induced or inflammatory lesions of the vessels supplying the tissue.

Adolescent↗
PubMed2004

Role of the C-terminal lysine residues of streptococcal surface enolase in Glu- and Lys-plasminogen-binding activities of group A streptococci.

Streptococcal surface enolase (SEN) is a major plasminogen-binding protein of group A streptococci. Our earlier biochemical studies have suggested that the region responsible for this property is likely located at the C-terminal end of the SEN molecule. In the present study, the gene encoding SEN was cloned from group A streptococci M6 isolate D471. A series of mutations in the sen gene corresponding to the C-terminal region (428KSFYNLKK435) of the SEN molecule were created by either deleting one or more terminal lysine residues or replacing them with leucine. All purified recombinant SEN proteins with altered C-terminal ends were found to be enzymatically active and were analyzed for their Glu- and Lys-plasminogen-binding activities. Wild-type SEN bound to Lys-plasminogen with almost three times more affinity than to Glu-plasminogen. However, the recombinant mutant SEN proteins with a deletion of Lys434-435 or with K435L and K434-435L replacements showed a significant decrease in Glu- and Lys-plasminogen-binding activities. Accordingly, a streptococcal mutant expressing SEN-K434-435L showed a significant decrease in Glu- and Lys-plasminogen-binding activities. Biochemical and functional analyses of the isogenic mutant strain revealed a significant decrease in its abilities to cleave a chromogenic tripeptide substrate, acquire plasminogen from human plasma, and penetrate the extracellular matrix. Together, these data indicate that the last two C-terminal lysine residues of surface-exposed SEN contribute significantly to the plasminogen-binding activity of intact group A streptococci and hence to their ability to exploit host properties to their own advantage in tissue invasion.

Bacterial Proteins↗
PubMed1997

Plasminogen in proliferative vitreoretinal disorders.

OBJECTIVE: Intravitreal fibrin formation is a frequent observation after vitrectomy performed for a variety of vitreoretinal disorders including proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), and endophthalmitis. Plasminogen activators (PA) have been used for the management of this postoperative complication. This approach requires the presence of plasminogen, the substrate for PA mediated fibrinolysis, in the vitreal cavity. METHODS: Quantification of plasminogen in the vitreous of 60 patients with PVR, PDR, and macular pucker was performed by streptokinase mediated activation using a chromogenic substrate. The presence of immunoreactive plasminogen was confirmed by immunoblot analysis of vitreal proteins and immunocytochemistry of surgically removed epiretinal membranes. RESULTS: Plasminogen levels were dramatically increased in the vitreous of PVR and PDR patients compared with macular pucker patients and normal controls. Staining for plasminogen in epiretinal membranes was confined to the extracellular matrix. Predominant staining of perivascular areas in PDR specimens indicated that breakdown of the blood-retinal barrier is an important source of intravitreal plasminogen in that condition. CONCLUSION: Plasminogen may play a role in traction membrane formation in PVR and PDR. Our biochemical analysis of presurgical vitreous indicates that there may be abundant substrate for PA mediated fibrinolysis in the vitreous cavity after vitrectomy.

Eye Diseases↗