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PubMedDate not supplied

[The effect of kringles K1-3, K4 and K5 on lysis of fibrin clots caused by the activation of Glu- and Lys-plasminogen by a tissue activator].

Kringles K1-3, K4 and K5 are studied for their effect on tissue plasminogen activator-induced fibrin clot lysis in the presence of Glu- and Lys-plasminogen. It is established that kringles K4 and K5 inhibit fibrinolysis of Glu-plasminogen, and K1-3--that of Lys-plasminogen. The role of plasminogen molecule kringles in the plasminogen interaction with fibrin polymer is discussed.

Blood Coagulation Tests↗
PubMed1985

Plasminogen activation in diabetes mellitus: normalization of blood sugar levels improves impaired enzyme kinetics in vitro.

We have demonstrated previously that fibrin enhanced plasmin formation by the vascular plasminogen activator was significantly impaired, when components isolated from the plasma of three uncontrolled diabetic patients (type I) were used to study plasminogen activation in vitro. In the present study it can be demonstrated that functional properties of the vascular plasminogen activators as well as of the plasminogens from the same three diabetic patients are significantly improved after normalization of blood sugar levels and improvement of HbA1c values. Most pronounced the Km of diabetic vascular plasminogen activator in the presence of fibrin returned to normal values, and for diabetic plasminogen the prolonged lag period until maximal plasmin formation occurred was shortened to almost control values. From these data we conclude that the observed abnormalities of in vitro fibrinolysis are not primarily associated with the diabetic disease, but might be secondary to metabolic disorders caused by diabetes.

Adult↗
PubMed1987

Selective fibrinolytic activity of recombinant non-glycosylated human pro-urokinase (single-chain urokinase-type plasminogen activator) from bacteria.

To assess their therapeutic value recombinant non-glycosylated human pro-urokinase (cPUK) and recombinant non-glycosylated human low molecular mass urokinase (cLUK) both obtained from genetically transformed bacteria were compared with respect to their thrombolytic efficacy and their potential to induce systemic plasminogen activation which impairs the coagulation system. The investigations were performed in in vitro and in vivo test systems. In vitro, both substances significantly and concentration-dependently lysed radiolabelled human thrombi in rotating loops of tubes (Chandler-loops) with equivalent efficacy. Fibrinolytic activity of cLUK was accompanied by a decrease in alpha 2-antiplasmin, plasminogen and fibrinogen. In contrast, cPUK did not change the plasminogen and fibrinogen levels and induced a substantially smaller decline in alpha 2-antiplasmin than cLUK. In the lysis of pulmonary embolized radiolabelled blood clots in anesthetized rabbits cPUK and cLUK dose-dependently exerted significant effects of similar extent. Whereas cLUK significantly decreased plasma levels of alpha 2-antiplasmin, plasminogen and fibrinogen, cPUK caused only a marginal decrease in alpha 2-antiplasmin and left the plasminogen and fibrinogen levels unchanged. The results indicate that cPUK exerts fibrinolytic efficacy without systemic plasminogen activation and breakdown of fibrinogen. Therefore, cPUK might be expected to be a more specific and safer thrombolytic agent than urokinase and other traditional fibrinolytics.

Amino Acid Sequence↗
PubMed1988

Modulation of plasminogen activator activity in human endometrial adenocarcinoma cells by basic fibroblast growth factor and transforming growth factor beta.

Human endometrial adenocarcinoma HEC-1-A and HEC-1-B cells produce and secrete the urokinase-type plasminogen activator and trace amounts of the tissue-type plasminogen activator. The two clones, which originate from the same tumor, possess high affinity binding sites for basic fibroblast growth factor (bFGF) and they respond to the addition of human recombinant bFGF with an increase of the synthesis and secretion of urokinase-type and tissue-type plasminogen activators and with an increase in cell proliferation. Transforming growth factor beta, (TGF beta), when added alone or 6 h before bFGF, induces an increase of plasminogen activator synthesis in both cell lines and stimulates the production of the endothelial cell-type plasminogen activator inhibitor in HEC-1-A cells, but not in HEC-1-B cells. Moreover, TGF beta inhibits basal proliferation of both cell lines and suppresses the mitogenic activity of bFGF. We have previously demonstrated that HEC-1-A and HEC-1-B cells produce significant amounts of bFGF. On the basis of the well-established coordinate modulation of solid tumor growth and plasminogen activator production, our data suggest that bFGF may contribute, in an autocrine fashion, to the development of endometrial carcinomas. Moreover, endometrial tumor cells appear also to be a target for TGF beta. Our results demonstrate also that significant qualitative and quantitative differences in the response to growth factors exist in clones derived from the same tumor, and support the view that the properties of in vivo tumors cannot be extrapolated from results obtained with a single isolate of tumor cells.

Adenocarcinoma↗
PubMed1985

Plasminogen activator activity in bone metastases of prostatic carcinomas as compared to primary tumors.

The plasminogen activator content of extracts of 14 prostatic carcinomas and the respective bone metastases was determined and found to be at an average 1.5 times higher in the extracts from bone metastases than in the primary tumors. Furthermore, the relative contribution of the two known types of plasminogen activators, urokinase-type (u-PA) and tissue-type (t-PA), was evaluated using specific antibodies. About 70% of the plasminogen activator activity in the primary tumors was inhibited by anti-urokinase IgG, whereas the same antibody nearly completely inhibited the plasminogen activator activity in extracts from bone metastases. Using antibodies against t-PA about 30% of the plasminogen activator activity could be quenched in extracts of primary tumors but less than 10% in extracts of bone metastases. Further studies revealed that the increased amount of u-PA in extracts of bone metastases is not caused by different extractability but is also reflected by a relative increase in the amount of u-PA demonstrable by immune histochemical techniques using anti-urokinase IgG. Upon purification, the predominant plasminogen activator from extracts of bone metastases could also be identified physicochemically as urokinase.

Adenocarcinoma↗
PubMed1983

The role of plasminogen activator in ovulation.

The role of plasminogen activator in ovulation was investigated using the inhibitor, trans-aminomethylcyclohexane carboxylic acid (t-AMCHA). In the regular cycle rat, the plasminogen activator activity of the follicles increased from the diestrus to the estrus phase. In the latter phase, a proteolytic enzyme which was not inhibited by t-AMCHA appeared. After ovulation, the plasminogen activator activity decreased. When ovulation was induced in immature rats by pregnant mare serum gonadotrophin and human chorionic gonadotrophin, remarkable fibrinolytic activity appeared in the ovaries immediately before ovulation. When t-AMCHA was given in the ovulation-induced rats, the fibrinolytic activity of the ovaries was suppressed, the number of ovulated ova decreased and the timing of ovulation was delayed. When t-AMCHA solution was given to rats in the proestrus phase, ovulation was almost completely suppressed, but aprotinin solution exerted no effect on ovulation. These results suggest that plasminogen activator is a key enzyme in ovulation, and that the chain reaction from plasminogen activator to proteolytic enzyme (including collagenase) is of greater importance than that of plasminogen activator to plasmin.

Animals↗
PubMed1984

Isolation and characterization of a urokinase-type plasminogen activator (Mr = 54,000) from cultured human endothelial cells indistinguishable from urinary urokinase.

A urokinase-type plasminogen activator secreted by subcultured normal human umbilical vein endothelial cells was purified and compared to urinary urokinase (Mr = 54,000). The enzyme was isolated from serum-free conditioned medium in the presence of 0.1% (v/v) Triton X-100 by p-aminobenzamidine-agarose affinity chromatography, followed by Sephacryl S-200 gel filtration, followed by immunoadsorption chromatography on affinity purified specific anti-urokinase IgG-Sepharose CL-4B. This plasminogen activator form was obtained from the culture medium with a yield of about 47% and specific activity of about 93,000 IU/mg of protein, and represented approximately 18% of the total multiple molecular plasminogen activator activity forms present in endothelial cell conditioned medium. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme showed a single band of plasminogen activator activity with an estimated molecular weight of about 54,000 that was completely inhibited by diisopropyl fluorophosphate (DFP) as well as a single band of radioactivity with similar molecular weight for both the isolated L-[4,5-3H]leucine and [3H]DFP-labeled enzyme. The radiolabeled protein focused as a single major band with a pI value of pH 8.5. The endothelial cell activator and urokinase appeared to be identical in terms of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, location of the [3H]DFP-labeled active site in the Mr = 33,000 heavy chain and [3H]DFP-labeled active site tryptic peptide, and two-dimensional 125I-labeled tryptic peptide maps. In quenching experiments of the fibrinolytic activities using affinity purified specific anti-urokinase IgG the endothelial cell-derived activator and urokinase appeared to be immunochemically identical, but unrelated to tissue plasminogen activator. These results indicate that the Mr = 54,000 urokinase-type plasminogen activator from cultured normal human endothelial cells is similar to, or identical with, Mr = 54,000 urinary urokinase.

Cells, Cultured↗
PubMed1982

An enhancing effect of poly-lysine on the activation of plasminogen.

This study demonstrates that poly-lysine mimics the cofactor (enhancing) function of fibrin that is seen in tissue activator-induced plasminogen activation. Additionally, and in contrast to fibrin, poly-lysine exhibited an enhancing effect on low molecular weight (and not high molecular weight) urokinase-induced plasminogen activation. A mechanism is proposed for this enhancement that involves the rendezvous and local concentration of plasminogen and plasminogen activator molecules on the lysine polymer. All components were able to bind to immobilized poly-lysine making the proposed mechanism feasible. It was possible to elute the activators and mini-plasminogen and plasmin which required 1 M lysine for elution, suggesting specific binding involving lysine binding sites. The enhancing effect was specific for poly-D- and L-lysine and poly-L-ornithine, which has a similar structure. The use of poly-lysine can lead to a better standardization and increased sensitivity of indirect two-step assays for plasminogen activators employing synthetic chromogenic substrates.

Binding Sites↗
PubMed1995

The plasminogen activator inhibitor system in bone cell function.

The plasminogen activator (PA)/plasmin pathway has been implicated in a variety of physiologic and pathologic processes that require tissue remodeling and cell motility. The pathway is highly regulated and results in the generation of the broad spectrum serine protease, plasmin, from the zymogen plasminogen. Urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) are produced by osteoblasts, as are the specific inhibitor plasminogen activator inhibitor-1 (PAI-1) and a cellular receptor for uPA. Little is known about regulation of the receptor, but the other 3 components of the pathway are regulated differentially by various osteotropic hormones and local factors. Several roles have been proposed for this pathway in bone. These involve proteolytic activation of procollagenase and latent growth factors, such as transforming growth factor beta (TGF beta) and insulin-like growth factor (IGF), as well as cell motility as a result of pericellular proteolysis. The roles of this pathway in bone remodeling may not be confined to proteolytic events, because uPA has been reported to act as a mitogen on osteoblast-like cells. This effect is independent of proteolytic activity but requires the growth factor domain of uPA to bind to uPA cellular receptors. If the plasminogen activator/plasmin pathway encompasses these roles, it would serve to couple formation and resorption of bone in a highly regulated manner.

Animals↗
PubMed1994

Inactivation of human anaphylatoxin C5a and C5a des-Arg through cleavage by the plasminogen activator activity of a human fibrosarcoma cell line.

The HT-1080 human fibrosarcoma cell line exhibited a plasminogen-dependent ability to inactivate recombinant anaphylatoxin C5a or zymosan-activated serum. The inactivation was obtained at physiological levels of both plasminogen (2 microM) and C5a (1-5 nM). Inactivated C5a and zymosan-activated serum were no longer able to induce chemotaxis and degranulation of neutrophils. Inactivation of C5a paralleled the emergence of plasmin activity, assayed by cleavage of the synthetic substrate H-D-valyl-L-leucyl-L-lysine-p-nitroanilide (S-2251). Both C5a inactivation and S-2251 cleavage were inhibited by the plasmin inhibitor alpha 2-antiplasmin, the urokinase inhibitor amiloride, and by anti-urokinase antibodies. In a cell-free system, inactivation of C5a was shown to depend on the simultaneous presence of urokinase and plasminogen and was inhibited by alpha 2-antiplasmin and by anti-urokinase antibodies. SDS-polyacrylamide electrophoresis demonstrated the cleavage of C5a by the plasminogen activation system and inhibition of the cleavage by amiloride. Amino acid sequencing of the band corresponding to the C5a degradation product revealed that C5a was cleaved at positions Lys14-His15 and Arg40-Ile41; cleavage at position Arg40-Ile41 seemed to be responsible for the loss of activity. Since neoplastic cells extensively produce and exhibit plasminogen activator activity, the present observations suggest that plasminogen activation may, by inactivation of C5a, reduce the anti-tumor immune response and support the immunological escape phenomenon of tumors.

Amino Acid Sequence↗
PubMed1993

Kringle glycosylation in a modified human tissue plasminogen activator improves functional properties.

Native tissue plasminogen activator (ntPA) has a variable glycosylation site on its kringle-2 domain. We have examined the effects of kringle glycosylation on functional properties by studying the simplified tPA molecule, tPA-6. tPA-6 is composed of kringle-2 and the serine protease domains and, like ntPA, cells expressing tPA-6 process it into two glycoforms: the monoglycosylated tPA-6-primary (tPA-6P, type II) with N-linked glycosylation at Asn-448 in the serine protease domain and diglycosylated tPA-6-variant (tPA-6V, type I) with glycosylation at Asn-448 and at Asn-184 in kringle-2. When the two glycoforms were separated, we found that purified tPA-6V had reduced fibrin-stimulated plasminogenolytic activity toward Glu-plasminogen when compared to purified tPA-6P. However, in the presence of fibrin, tPA-6V unexpectedly exhibited a sixfold increase in selectivity toward Lys-plasminogen. In addition, tPA-6V was less susceptible than tPA-6P to plasmin-mediated conversion to the two-chain form. By site-directed mutagenesis of tPA-6, we eliminated variable glycosylation at Asn-184 and engineered a new glycosylation signal at a remnant site in the kringle. This derivative, designated tPA-6D, was secreted with complete kringle glycosylation. Like the naturally occurring tPA-6V, tPA-6D had lower rates of fibrin-stimulated Glu-plasminogen activation, increased specificity toward Lys-plasminogen, and greater resistance to plasmin digestion. Although the activity of tPA-6D could be stimulated by fibrin, its activity was not stimulated significantly by fibrinogen, and in human plasma the rate of fibrinogen depletion was reduced threefold. Although fibrin binding to kringle-2 of tPA-6D was slightly improved, there was a substantial increase in the dissociation constant (kd) for lysine binding, demonstrating a lack of correlation between these ligand-binding sites. Overall, our data demonstrate the marked effect of kringle glycosylation on functional properties. In addition, we have generated a derivative with properties that potentially improve clot specificity and single-chain half-life and reduce the potential for plasminogen activation in the plasma.

Base Sequence↗
PubMed1993

Macrophage and foam cell release of matrix-bound growth factors. Role of plasminogen activation.

We have determined whether macrophage derived-foam cells, a prominent component of the atherosclerotic lesion, express more urokinase-type plasminogen activator (uPA) and whether their ability to generate plasmin stimulates the release of matrix-bound growth factors. Steady state levels of uPA mRNA and both membrane and intracellular uPA activities were significantly increased in foam cells. When cultured on cell-derived matrices containing bound 125I-basic fibroblast growth factor (bFGF), both macrophage and foam cells released intact 125I-bFGF into their media. The release of 125I-bFGF by either cell was significantly enhanced in the presence of plasminogen. However, foam cells, which expressed more membrane uPA, released more 125I-bFGF than control cells. The release of matrix-bound bFGF was independent of heparanase activity, since neither macrophage nor foam cells degraded 35SO4-labeled heparan sulfate proteoglycans. In addition, media derived from foam cells cultured on cell-derived matrices in the presence of plasminogen had increased levels of transforming growth factor (TGF) beta activity as compared to cells grown in the absence of plasminogen. In contrast, plasminogen had no effect on TGF-beta activity recovered in the media of foam cells grown on plastic. Moreover, when macrophage were cultured on matrices containing bound 125I-TGF-beta, the release of labeled TGF-beta was increased in the presence of plasminogen. This is the first demonstration that foam cells can release two important growth regulators, bFGF and TGF-beta, from the extracellular matrix, and provides a mechanism by which macrophage and foam cells can stimulate atherosclerotic lesion development.

Animals↗
PubMed1998

Evaluation of the factors contributing to fibrin-dependent plasminogen activation.

Polymerized fibrin strongly enhances tissue plasminogen activator (tPA)-mediated plasminogen activation, concomitant with exposure of 'fibrin-specific' epitopes at 'Aalpha148-160' and 'gamma312-324'. To investigate which aspects of polymerization are involved in these activities, we explored the fibrin polymerization process by evaluating the ability of factor XIIIa-crosslinked fibrinogen polymers to expose 'fibrin-specific' epitopes and enhance plasminogen activation. Crosslinked normal fibrinogen, fibrinogen with deficient [des Bbeta1-42] or defective [Birmingham (AalphaR16H)] fibrin 'D:E' assembly sites ('E(A)'), or with defective end-to-end self-association sites ('D:D') [Cedar Rapids (gammaR275C)], exposed both 'fibrin-specific' epitopes and enhanced tPA-dependent plasminogen activation, whereas non-crosslinked fibrinogens showed minimal or no such activities. Epitope expression in crosslinked fibrinogen was retained in the presence of the fibrin E(A) site peptide homolog, gly-pro-arg-pro (GPRP), which inhibits fibrin D:E association, except for the Aalpha148-160 epitope in des Bbeta1-42 fibrinogen, which was not expressed. Fibrin prepared from crosslinked normal or abnormal fibrinogen, except for the des Bbeta1-42 fibrin epitopes, which were reduced or absent, expressed 'fibrin-specific' epitopes even in the presence of GPRP, which otherwise impairs such expression in non-crosslinked fibrin. Epitope exposure in fibrin prepared from non-crosslinked fibrinogen was nearly normal in Cedar Rapids fibrin (heterozygous D:D defect), but reduced in Birmingham fibrin (heterozygous E(A) defect), nil in des Bbeta1-42 fibrin (E(A) deficient), and absent in all cases in the presence of GPRP. In contrast, plasminogen activation stimulatory activity that had been exposed in crosslinked normal fibrinogen or in crosslinked des Bbeta1-42 or Cedar Rapids fibrin, was preserved to a large extent in the presence of GPRP, suggesting that once enhanced stimulatory activity and epitopes are exposed, they are not completely reversible. The findings indicate that end-to-end intermolecular associations (D:D) are not critical for 'fibrin-specific' epitope exposure, but that polymerization brought about in fibrinogen through factor XIIIa crosslinking, or in fibrin through 'D:E' interactions, is necessary for 'fibrin-specific' (more correctly, 'polymerization-specific') epitope exposure and enhancement of plasminogen activation.

Afibrinogenemia↗
PubMed2002

Spitz naevi may express components of the plasminogen activation system.

The plasminogen activation (PA) system is involved in the process of invasion and metastasis. Its major components are urokinase (uPA) and tissue-type plasminogen activator (tPA), plasminogen activation inhibitor type 1 and 2 (PAI-1 and PAI-2) and a receptor for urokinase (uPAR). In this study, the expression of plasminogen activation components in Spitz naevi was compared with that in common and dysplastic naevi on the one hand and primary cutaneous melanomas on the other. Spitz naevi had melanocytic positivity for uPA in 0% (0/36), tPA in 30% (6/20), PAI-1 in 10% (3/35), PAI-2 in 40% (8/21) and uPAR in 60% (13/21) of cases. This far exceeded the expression found in common (n = 25) and dysplastic (n = 15) naevi, which only showed melanocytic positivity for PAI-2 (20% and 15% respectively) and in one dysplastic naevus also for uPAR. This was much (for most components significantly) less than the proportion of primary melanomas with tumour cell positivity, which was 30% (11/38) for uPA, 80% (19/24) for tPA, 75% (28/38) for PAI-1, 80% (19/24) for PAI-2 and 80% (19/24) for uPAR. The main findings of this study are that Spitz naevi, firstly, may express plasminogen activator (tPA), inhibitors and the receptor of the PA system, but in a much smaller proportion than cutaneous melanomas; and secondly, do not express urokinase, whereas some of the melanomas do. uPA positivity may therefore be suggestive of melanoma. However, overlapping staining results imply that the PA system has limited value in the differential diagnosis between Spitz naevus and primary melanoma. As serine protease components are expressed, Spitz naevi may use this proteolytic machinery to accomplish matrix degradation, although in a more restricted, possibly transient manner than melanomas.

Biomarkers, Tumor↗
PubMed2001

Epidermal growth factor and pro-inflammatory cytokines regulate the expression of components of plasminogen activation system in U373-MG astrocytoma cells.

Cytokines and growth factors that influence both secretion of the extracellular matrix (ECM) proteins and migration of the cells decide about the final outcome of tissue remodelling. We have examined expression of the components of the plasminogen activation system in human astrocytoma U373-MG cells and found that interleukin 1beta (IL-1beta), tumour necrosis factor alpha TNF-alpha), interferon gamma (INF-gamma) and epidermal growth factor (EGF) specifically regulate the expression of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor type 1 (PAI-1) and protease nexin-1 (PN-1). We conclude that EGF and IFN-gamma are new important regulators of the plasminogen activation system in astrocytoma cells and, therefore, may influence turnover of extracellular matrix and migration of cells within the brain.

Amyloid beta-Protein Precursor↗
PubMed1998

Oestradiol regulation of the components of the plasminogen-plasmin system in MDA-MB-231 human breast cancer cells stably expressing the oestrogen receptor.

To understand the hormonal regulation of the components of the plasminogen-plasmin system in human breast cancer, we examined the oestradiol (E2) regulation of plasminogen activators (PAs), namely urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1) and uPA receptor (uPAR), in our model system. We used stable transfectants of the MDA-MB-231 human breast cancer cells that express either the wild-type (S30 cells) or the mutant 351asp-->tyr oestrogen receptor (ER) (BC-2 cells). Northern blot analysis showed that there was a concentration-dependent down-regulation of uPA, tPA and PAI-1 mRNAs by E2. In contrast, uPAR mRNA was not modulated by E2. The pure anti-oestrogen ICI 182,780 was able to block E2 action, indicating that the regulation of these genes is ER mediated. The E2 also inhibited the expression and secretion of uPA, tPA and PAI-1 proteins as determined by enzyme-linked immunosorbent assay (ELISA) in cell extracts (CEs) and conditioned media (CM). Zymography of the CM confirmed the inhibitory effect of E2 on uPA activity. Thus, we now report the regulation of uPA, PAI-1 and tPA by E2 in both mRNA and protein levels in ER transfectants. The association between down-regulation of the uPA by E2 and known E2-mediated growth inhibition of these cells was also explored. Our findings indicate that down-regulation of uPA by E2 is an upstream event of inhibitory effects of E2 on growth of these cells as the addition of exogenous uPA did not block the growth inhibition by E2.

Breast Neoplasms↗
PubMed1998

Plasminogen activator in acute myeloid leukaemic marrows: u-PA in contrast to t-PA in normal marrow.

Leukaemic and normal bone marrow samples were compared in terms of their content of the fibrinolytic agents, tissue plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA) and their inhibitors. plasminogen activator inhibitors 1 and 2 (PAI-1 and PAI-2). Normal marrow contained t-PA as the principal plasminogen activator, whereas in leukaemic marrow samples u-PA was the predominant activator. Both normal and leukaemic marrows contained PAI-1 in similar amounts, but whereas normal marrow contained significant amounts of PAI-2 the leukaemic marrows contained very little. Plasminogen activators were present in uncomplexed, active forms and plasmin-alpha2-antiplasmin complexes were generated locally more prominently in leukaemic marrows. u-PA associated with blast cells may contribute to the severe forms of haemorrhage sometimes occurring in myeloid types of leukaemia.

Acute Disease↗
PubMed2003

Relationships between activators and inhibitors of plasminogen, and the progression of small abdominal aortic aneurysms.

OBJECTIVE: plasmin is a common activator of the known proteolytic systems involved in the aneurysmal degradation, and is reported to be associated with the expansion of abdominal aortic aneurysms (AAA). The aim of this study was to study the activating pathways of plasminogen as predictors of the progression of AAA. MATERIALS AND METHODS: one hundred and twelve of 122 male patients with a small AAA (def.: +3cm) were interviewed, examined, had blood samples taken at diagnosis, and scanned annually for 1-5 years (mean 3.5 years), and referred for surgery if the AAA exceeded 5cm in diameter.A random sample of 70 of the 112 cases had plasma levels of urokinase-like-plasminogen activator (uPA), tissue-type-plasminogen activator (tPA), plasminogen-activator-inhibitor-1 (PAI-1), macrophage inhibiting factor (MIF), tumour-growth-factor-beta1 (TGF-beta1), homocysteine, and serum levels of IgA-antibodies against Chlamydia pneumoniae (IgA-CP) and Cotinine (a nicotine metabolite) measured. Spearmans correlation analysis was used for statistics. RESULTS: the annual expansion rate correlated positively with tPA, IgA-CP and S-Cotinine; r =0.37 (p=0.002), 0.29 (p=0.006) and 0.24 (p=0.038), while PAI1, uPA, TGF-beta1, homocysteine, and MIF did not. S-Cotinine did also correlate positively with tPA, r=0.24 (p=0.049). CONCLUSION: the aortic matrix degradation in AAA may be partly caused by an activation of plasminogen by tPA, but apparently not by uPA, which usually dominates matrix degradation. Smoking seems to be a factor for this pathway, while the pathways of IgA-CP and MIF, a new marker of aneurysmal progression, seem different. The latter observations suggest that other proteolytic pathways are involved in the aortic wall degradation in AAA.

Aged↗