Publications by authors named "Olga Plekhanova"

14 Publications

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Presentation and formatting of laboratory results: a narrative review on behalf of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group "postanalytical phase" (WG-POST).

Crit Rev Clin Lab Sci 2021 Aug 4;58(5):329-353. Epub 2021 Feb 4.

Department of Medical Biochemistry and Pharmacology, Laboratory Clinic, Haukeland University Hospital and Noklus, Haraldsplass Deaconess Hospital, Bergen, Norway.

In laboratory medicine, much effort has been put into analytical quality in the past decades, making this medical profession one of the most standardized with the lowest rates of error. However, even the best analytical quality cannot compensate for errors or low quality in the pre or postanalytical phase of the total testing process. Guidelines for data reporting focus solely on defined data elements, which have to be provided alongside the analytical test results. No guidelines on how to format laboratory reports exist. The habit of reporting as much diagnostic data as possible, including supplemental information, may lead to an information overload. Considering the multiple tasks physicians have to do simultaneously, unfiltered data presentation may contribute to patient risk, as important information may be overlooked, or juxtaposition errors may occur. As laboratories should aim to answer clinical questions, rather than providing sole analytical results, optimizing formatting options may help improve the effectiveness and efficiency of medical decision-making. In this narrative review, we focus on the underappreciated topic of laboratory result reporting. We present published literature, focusing on the impact of laboratory result report formatting on medical decisions as well as approaches, potential benefits, and limitations for alternative report formats. We discuss influencing variables such as, for example, the type of patient (e.g. acute versus chronic), the medical specialty of the recipient of the report, the display of reference intervals, the medium or platform on which the laboratory report is presented (printed paper, within electronic health record systems, on handheld devices, etc.), the context in which the report is viewed in, and difficulties in formatting single versus cumulative reports. Evidence on this topic, especially experimental studies, is scarce. When considering the medical impact, it is of utmost importance that laboratories focus not only on the analytical aspects but on the total testing process. The achievement of high analytical quality may be of minor value if essential results get lost in overload or scattering of information by using a non-formatted tabular design. More experimental studies to define guidelines and to standardize effective and efficient reporting are most definitely needed.
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http://dx.doi.org/10.1080/10408363.2020.1867051DOI Listing
August 2021

Clinical Comparison of Super Pulse Thulium Fiber Laser and High-Power Holmium Laser for Ureteral Stone Management.

J Endourol 2021 Jun 13;35(6):795-800. Epub 2021 Jan 13.

Department of Urology and Andrology, IPPE of A.I. Burnazyan SSC FMBC, FMBA of Russia, Moscow, Russia.

To evaluate the efficacy of new super pulse thulium fiber laser (SP TFL) and compare it with holmium laser for ureterolithotripsy. A total of 174 patients with solitary ureteral calculi were enrolled in 2016 to 2018. Stone sizes ranged between 0.6 and 2.4 cm. The SP TFL FiberLase U2 and 120H Ho:YAG laser with fibers diameters of 400 and 365 μm, respectively, were used. The laser settings were 1 J × 10 Hz = 10 W for both devices. All patients were randomized into two groups. The age, stone size, location, and density were comparable in both groups. The evaluated parameters were operation time, endoscopic view quality, retropulsion grade, stone-free rate, and complication rate. The total operation time and lasering time were longer in the Ho:YAG group (24.7 ± 0.7 minutes 32.4 ± 0.7 minutes,  = 0.05), and postoperative stenting was necessary in one four cases, respectively. At 30 days of follow-up, no residual stones were observed in the SP TFL group ( five cases of Ho:YAG). SP TFL technology was associated with excellent efficacy/safety ratio. The SP TFL may be considered as a viable alternative to Ho:YAG laser stone management.
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http://dx.doi.org/10.1089/end.2020.0581DOI Listing
June 2021

Thermoexpandable Urethral Nickel-Titanium Stent Memokath for Managing Urethral Bulbar Stricture After Failed Urethroplasty.

J Endourol Case Rep 2020 17;6(3):147-149. Epub 2020 Sep 17.

Department of Urology, D.D. Pletnev City Clinical Hospital, Moscow Health Department, Moscow, Russia.

Urethral stenting became popular two decades ago, but nowadays its frequency is slightly decreased because of the rising application of urethroplasty. Today urethral stenting is reserved only for failure after urethral reconstruction or in cases when the plastic surgery is unfavorable. The Memokath stent (Pnn Medical A/S, Kvistgaard, Denmark) is manufactured from a biocompatible alloy of nickel and titanium and known to be the most popular in this field. A 38-year-old man with a history of 9 years Memokath urethral stenting was admitted to our clinic with obstructive lower urinary tract symptoms. The indication for Memokath stenting was repeated recurrences after endoscopic and reconstructive operations. The plain radiography showed a normal position of the stent and only the endoscopic examination revealed its total calcification. New superpulse thulium fiber laser has been used to free the stent from the stones and safely remove it without additional urethral injury. The postoperative time was within normal limits, the catheter was removed on the fourth day after operation. Three months follow-up was without stricture recurrence. We continue active surveillance of the patient. The calcification of the stent could be properly diagnosed endoscopically; the Memokath stent could be safely removed in 9 years after implantation; thulium fiber laser is effective and safe in the management of encrusted urethral stent.
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http://dx.doi.org/10.1089/cren.2019.0146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580599PMC
September 2020

Oligonucleotide Microarrays Identified Potential Regulatory Genes Related to Early Outward Arterial Remodeling Induced by Tissue Plasminogen Activator.

Front Physiol 2019 30;10:493. Epub 2019 Apr 30.

Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russia.

Constrictive vascular remodeling limiting blood flow, as well as compensatory outward remodeling, has been observed in many cardiovascular diseases; however, the underlying mechanisms regulating the remodeling response of the vessels remain unclear. Plasminogen activators (PA) are involved in many of the processes of vascular remodeling. We have shown previously that increased levels of tissue-type PA (tPA) contributes to outward vascular remodeling. To elucidate the mechanisms involved in the induction of outward remodeling we characterized changes in the expression profiles of 8799 genes in injured rat carotid arteries 1 and 4 days after recombinant tPA treatment compared to vehicle. Periadventitial tPA significantly increased lumen size and vessel area, encompassed by the external elastic lamina, at both one and 4 days after treatment. Among 41 differentially expressed known genes 1 day after tPA application, five genes were involved in gene transcription, five genes were related to the regulation of vascular tone [for example, thromboxane A2 receptor (D32080) or non-selective-type endothelin receptor (S65355)], and eight genes were identified as participating in vascular innervation [for example, calpain (D14478) or neural cell adhesion molecule L1 (X59149)]. Four days after injury in tPA-treated arteries, four genes, regulating vascular tone, were differentially expressed. Thus, tPA promotes outward arterial remodeling after injury, at least in part, by regulating expression of genes in the vessel wall related to function of the nervous system and vascular tone.
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http://dx.doi.org/10.3389/fphys.2019.00493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502959PMC
April 2019

Clinical significance of cytogenetic changes in childhood T-cell acute lymphoblastic leukemia: results of the multicenter group Moscow-Berlin (MB).

Leuk Lymphoma 2019 02 1;60(2):426-432. Epub 2018 Aug 1.

i Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Charité CVK, Universitätsmedizin Berlin , Berlin , Germany.

The prognostic significance of genetic lesions in T-cell ALL still needs to be elucidated. Karyotyping and FISH were performed in samples from 120 patients with T-cell ALL registered in the trial Moscow-Berlin 2008. Most frequent rearrangements were TLX3 (N = 29; 24%) and TAL1 (N = 18; 15%), followed by KMT2A (N = 6; 5%), TLX1 (N = 5; 4.2%), and 11p13-15 (N = 5; 4.2%). In 16.7% of patients, the karyotype was normal, and in 30.8% 'other' aberrations were seen. Patients with a normal karyotype, TAL1, or KMT2A rearrangements had the most favorable outcome (probability of event free survival (pEFS): 82% ± 6%), while prognosis for patients with TLX3 and TLX1 rearrangements and 'other' aberrations was less favorable (pEFS: 62% ± 6%). Worst outcome was observed for five patients with 11p rearrangements (pEFS: 20% ± 18%). In summary, three subgroups of patients with T-cell ALL with significantly different outcomes could be defined by cytogenetic profiling.
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http://dx.doi.org/10.1080/10428194.2018.1485904DOI Listing
February 2019

Urokinase and urokinase receptor participate in regulation of neuronal migration, axon growth and branching.

Eur J Cell Biol 2016 Sep 3;95(9):295-310. Epub 2016 Jun 3.

Department of Biochemistry and Molecular Medicine, Faculty of Medicine, M.V. Lomonosov Moscow State University, Lomonosovsky av. 31/5, 119192 Moscow, Russian Federation; Laboratory of Molecular Endocrinology, Russian Cardiology Research Center, 3rd Cherepkovskaya 15a, 12155 Moscow, Russian Federation.

Purpose: Recent findings indicate the significant contribution of urokinase and urokinase receptor (uPA and uPAR) in the processes of nerve regeneration, however, their role in axonal growth and branching is unclear. Using a 3D model of mouse Dorsal Root Ganglia (DRG) explants, differentiated into neurons Neuro 2a cells and transgenic mice lacking the urokinase gene, we studied the involvement of the uPA/uPAR system in the neural cell migration, neurite outgrowth, elongation and branching.

Results: uPA and uPAR are expressed in the growth cones of axons. Using an ex vivo model of DRG explants in Matrigel we have found that uPA inhibition attenuates neural cell migration and axonal growth, pointing to an important role of urokinase in these processes. Apparently, uPA mediates its effects through its specific receptor uPAR: anti-uPAR antibody, which blocks the uPA binding to uPAR, stimulates axon branching and attenuates neural cell migration from DRG explants. Simultaneous inhibition of uPA and uPAR almost completely prevents the axonal outgrowth from explants into the Matrigels. Experiments in vitro using Neuro 2a cells differentiated into neurons demonstrate that administration of exogenous uPA increases the neurite growth rate (elongation), most likely via the interaction of uPA with uPAR. Blocking of uPAR stimulates neurite formation and enhances branching of preexisting neurites. The results obtained on DRG explants from transgenic mice lacking uPA gene support the assumption that uPA stimulates neurite growth via uPA/uPAR interaction and uPAR role in axons branching and neural cell migration.

Conclusions: The uPA/uPAR system plays an essential role in neural cell migration, axonal growth and branching.
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http://dx.doi.org/10.1016/j.ejcb.2016.05.003DOI Listing
September 2016

A Novel Three-Colour Fluorescence in Situ Hybridization Approach for the Detection of t(7;12)(q36;p13) in Acute Myeloid Leukaemia Reveals New Cryptic Three Way Translocation t(7;12;16).

Cancers (Basel) 2013 Mar 11;5(1):281-95. Epub 2013 Mar 11.

Leukaemia and Chromosome Research Laboratory, Division of Biosciences, Brunel University, London, Middlesex UB8 3PH, UK.

The t(7;12)(q36;p13) translocation is a recurrent chromosome abnormality that involves the ETV6 gene on chromosome 12 and has been identified in 20-30% of infant patients with acute myeloid leukaemia (AML). The detection of t(7;12) rearrangements relies on the use of fluorescence in situ hybridization (FISH) because this translocation is hardly visible by chromosome banding methods. Furthermore, a fusion transcript HLXB9-ETV6 is found in approximately 50% of t(7;12) cases, making the reverse transcription PCR approach not an ideal screening method. Considering the report of few cases of variant translocations harbouring a cryptic t(7;12) rearrangement, we believe that the actual incidence of this abnormality is higher than reported to date. The clinical outcome of t(7;12) patients is believed to be poor, therefore an early and accurate diagnosis is important in the clinical management and treatment. In this study, we have designed and tested a novel three-colour FISH approach that enabled us not only to confirm the presence of the t(7;12) in a number of patients studied previously, but also to identify a cryptic t(7;12) as part of a complex rearrangement. This new approach has proven to be an efficient and reliable method to be used in the diagnostic setting.
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http://dx.doi.org/10.3390/cancers5010281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730311PMC
March 2013

Plasma urokinase antigen and C-reactive protein predict angina recurrence after coronary angioplasty.

Heart Vessels 2014 Sep 22;29(5):611-8. Epub 2013 Sep 22.

Laboratory of Angiogenesis, Cardiology Research Center, 3rd Cherepkovskaya, 15a, Moscow, 121552, Russia,

This study evaluates the predictive value of several biochemical indices of the coagulation-fibrinolysis system, platelet function, and inflammatory state for angina recurrence after successful percutaneous transluminal coronary angioplasty (PTCA). We measured preprocedural and follow-up plasma levels of C-reactive protein (CRP), fibrinogen, and urokinase plasminogen activator antigen (uPA), plasminogen activator inhibitor-1 (PAI-1) activity, tissue plasminogen activator activity, and adenosine diphosphate-induced platelet aggregation in 53 patients with chronic stable angina who underwent successful elective PTCA of single hemodynamically significant lesions in coronary arteries. All patients were followed up for 12 months after PTCA. The Cox proportional hazards model was used to assess the association of variables with angina recurrence rate. At the end of the follow-up, 16 patients had angina recurrence. Among 36 clinical, biochemical, and angiographic variables, the duration of stable angina more than 12 months before PTCA (χ (2) = 5.73; P = 0.02, hazard ratio (HR) 3.7, 95 % confidence interval (CI) 1.26-10.6), high baseline levels of CRP (>7 mg/l) (χ (2) = 8.34; P = 0.004, HR 2.9, 95 % CI 1.4-5.9), uPA antigen baseline (>1 ng/ml) (χ (2) = 17.11; P = 0.0001, HR 11.5, 95 % CI 3.6-36.7) and 48 h after PTCA (χ (2) = 15.73; P = 0.0001, HR 8.8, 95 % CI 3.01-25.96), baseline PAI-1 activity (>18 IU/ml) (χ (2) = 9.37; P = 0.002, HR 7.6, 95 % CI 2.07-27.84) were significant predictors of recurrent angina by univariate analyses. According to stepwise multivariate analyses, only the levels of plasma uPA antigen and serum CRP were shown to be significant independent predictors of angina recurrence (multivariate uPA χ (2) = 8.22, P = 0.004, HR 6.2, 95 % CI 1.78-21.67; CRP χ (2) = 4.09, P = 0.04, HR 1.9, 95 % CI 1.02-3.68). High preprocedural plasma uPA and serum CRP levels are indicative of angina recurrence after successful PTCA, and are valuable for the prognosis of restenosis.
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http://dx.doi.org/10.1007/s00380-013-0407-1DOI Listing
September 2014

Regulation of arterial remodeling and angiogenesis by urokinase-type plasminogen activator.

Can J Physiol Pharmacol 2009 Apr;87(4):231-51

Cardiology Research Centre, Laboratory of Molecular Endocrinology, Moscow 121552, Russia.

A wide variety of disorders are associated with an imbalance in the plasminogen activator system, including inflammatory diseases, atherosclerosis, intimal hyperplasia, the response mechanism to vascular injury, and restenosis. Urokinase-type plasminogen activator (uPA) is a multifunctional protein that in addition to its fibrinolytic and matrix degradation capabilities also affects growth factor bioavailability, cytokine modulation, receptor shedding, cell migration and proliferation, phenotypic modulation, protein expression, and cascade activation of proteases, inhibitors, receptors, and modulators. uPA is the crucial protein for neointimal growth and vascular remodeling. Moreover, it was recently shown to be implicated in the stimulation of angiogenesis, which makes it a promising multipurpose therapeutic target. This review is focused on the mechanisms by which uPA can regulate arterial remodeling, angiogenesis, and cell migration and proliferation after arterial injury and the means by which it modulates gene expression in vascular cells. The role of domain specificity of urokinase in these processes is also discussed.
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http://dx.doi.org/10.1139/Y08-113DOI Listing
April 2009

Oligonucleotide microarrays reveal regulated genes related to inward arterial remodeling induced by urokinase plasminogen activator.

J Vasc Res 2009 24;46(3):177-87. Epub 2008 Sep 24.

Molecular Endocrinology Laboratory, Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russia.

Accumulating evidence suggests that urokinase plasminogen activator (uPA) is involved in vascular remodeling and lumen stenosis after angioplasty and stenting. We have shown previously that increased uPA expression greatly promotes neointima formation and inward arterial remodeling after balloon injury. To evaluate the role of inflammation in early mechanisms responsible for inward arterial remodeling induced by uPA and elucidate the mechanisms of remodeling, we characterized changes in the expression profiles of 8,799 genes in injured rat carotid arteries 1 and 4 days after recombinant uPA treatment compared to vehicle. We used a standard model of the balloon catheter injury of the rat carotid followed by periadventitial application to the injured vessel of either uPA dissolved in Pluronic gel, or plain gel. Vessels were harvested and analyzed by immunohistochemistry, morphometry, microarray gene expression profiling and quantitative RT-PCR. Periadventitial application of uPA significantly reduced lumen size and vessel area encompassed by the external elastic lamina at both 1 and 4 days after treatment. Inflammatory cells accumulated in the arterial adventitia at both 1 and 4 days after uPA treatment. On the 4th day, increases in the areas and arterial cell numbers of all arterial layers were found. Among 79 differentially expressed known genes 1 day after uPA application, 12 proinflammatory genes, including TNF-alpha and TACE, and 15 genes related to mitochondrial metabolism and oxidative stress regulation were identified. Four days after injury in uPA-treated arteries, 3 proinflammatory and 2 oxidation-related genes were differentially expressed. We conclude that uPA likely promotes inward arterial remodeling by regulating oxidative stress and inflammation after arterial injury.
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http://dx.doi.org/10.1159/000156703DOI Listing
May 2009

Urokinase plasminogen activator in injured adventitia increases the number of myofibroblasts and augments early proliferation.

J Vasc Res 2006 7;43(5):437-46. Epub 2006 Aug 7.

Cardiology Research Centre, Moscow, Russia.

Myofibroblasts are involved in vessel remodeling during the development of hypertension as well as after angioplasty and aortocoronary grafting, but the mechanisms of myofibroblastic phenotypic modulation are not fully elucidated. We assessed the role of urokinase plasminogen activator (uPA) and its proteolytic activity in myofibroblast differentiation and the early proliferation following mechanical injury of the rat carotid adventitia. The effects of perivascular application of recombinant uPA (r-uPA), proteolytically inactive r-uPA(H/Q) and uPA neutralizing antibody were evaluated 4 days after surgical injury to the adventitia. The phenotype of adventitial cells was assessed using anti-alpha-smooth muscle actin (alpha-SM actin) antibody, anti-SM heavy chain myosin, anti-high-molecular-weight caldesmon, anti-smoothelin and anti-ED-1 antibodies, proliferation by the expression of proliferating cell nuclear antigen, and the size of the adventitia by quantitative morphometry. Four days after injury, the intensive immunostaining for urokinase appeared in the rat carotid artery adventitia. At the same time, the frequency of alpha-SM actin-positive adventitial cells was 1.8+/-1.1% in uninjured arteries and 25.2+/-5.4% in injured arteries (p<0.05), and the respective frequency of ED-1-positive cells 1.5+/-1.1 and 25.0+/-5.2%. The application of exogenous r-uPA doubled the numbers of alpha-SM actin-positive adventitial cells to 55.7+/-6.8% (p<0.05). ED-1-positive cells and proliferating cell nuclear antigen-positive cells as well as the size of the adventitia were also significantly increased after r-uPA compared with injury alone. In contrast, the proteolytically inactive r-uPA(H/Q) did not affect any parameters. The application of uPA neutralizing antibody attenuated the frequency of alpha-SM actin-positive cells to 12.6+/-3.5% (p<0.05), the frequency of ED-1-positive cells, and the numbers of adventitial cells. r-uPA stimulation of cultured human skin fibroblasts significantly increased the alpha-SM actin content in a concentration-dependent manner. In contrast, r-uPAH/Q did not induce changes in alpha-SM actin content. We conclude that uPA, which is upregulated in the injured adventitia, can augment adventitial cell accumulation, including myofibroblasts, and adventitia growth early after injury of the rat carotid artery adventitia by mechanisms involving proteolysis.
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http://dx.doi.org/10.1159/000094906DOI Listing
October 2006

Urokinase plasminogen activator stimulates vascular smooth muscle cell proliferation via redox-dependent pathways.

Arterioscler Thromb Vasc Biol 2006 Apr 2;26(4):801-7. Epub 2006 Feb 2.

Cardiology Research Center, Moscow, Russia.

Objective: We showed previously that increased urokinase plasminogen activator (uPA) expression contributes to vascular smooth muscle cell (VSMC) proliferation and neointima formation after injury. Proliferation of cultured rat aortic VSMCs induced by uPA was inhibited by the antioxidant ebselen. Because increases in VSMC reactive oxygen species (ROS) contribute to VSMC proliferation, we hypothesized that uPA increases ROS generation by regulating expression or activity of cellular oxidases.

Methods And Results: uPA stimulated ROS production to levels equivalent to angiotensin II as measured by electron spin resonance and fluorescent redox indicators (dichlorofluorescein diacetate, lucigenin, and hydroethidine). The increase in ROS was biphasic, with the first peak at 30 minutes and the second peak at 4 hours. uPA increased expression of the NAD(P)H oxidases Nox1 and Nox4 as measured by RT-PCR and Western blot analysis. Knockdown of Nox1 and Nox4 expression with small interfering RNA showed that both isoforms (Nox1>Nox4) contributed significantly to uPA-stimulated ROS production and VSMC proliferation. Transfection of VSMCs with uPA cDNA to increase endogenous uPA expression enhanced ROS production dramatically, suggesting that autocrine uPA production may be an important mechanism for uPA-mediated VSMC events.

Conclusions: These data show that uPA is an autocrine VSMC growth factor that increases ROS generated by both Nox1 and Nox4 oxidases.
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http://dx.doi.org/10.1161/01.ATV.0000207277.27432.15DOI Listing
April 2006

Plasminogen activator expression correlates with genetic differences in vascular remodeling.

J Vasc Res 2004 Nov-Dec;41(6):481-90. Epub 2004 Oct 28.

Center for Cardiovascular Research, Aab Institute of Biomedical Sciences and Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642, USA.

Intima-media thickening (IMT) of the carotid artery, a form of vascular remodeling, correlates well with coronary artery disease risk in humans. Vascular remodeling in response to blood flow is a complex process that critically involves altered cell matrix interactions. To gain insight into these events, we performed partial carotid ligation (left carotid (LCA) = low flow and right carotid (RCA) = high flow) in 2 inbred mouse strains: C57Bl/6J (C57) and FVB/NJ (FVB). To evaluate the role of the 2 major matrix-degrading systems, plasminogen activators (PAs) and matrix metalloproteinases (MMPs), we compared the expression of u-PA, t-PA, MMP-2 and MMP-9 in ligated carotids of C57 and FVB mice. The extent of remodeling was greater in response to low LCA than high RCA flow. Despite a similar decrease in LCA flow in both strains, maximal IMT volume was greater in FVB (82 +/- 7 x 10(-6) microm(3)) than in C57 (38 +/- 4 x 10(-6) microm(3)) after ligation. Among PAs and MMPs, increased expression of t-PA and u-PA correlated with increased IMT (p < 0.0005 and p < 0.001, respectively). MMP-2, MMP-9 and tissue inhibitors of metalloproteinase-2 expression also increased, but did not differ between strains. In summary, flow-induced IMT of the carotid is genetically determined and correlates with t-PA and u-PA expression in 2 inbred mouse strains.
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http://dx.doi.org/10.1159/000081804DOI Listing
January 2005

Contrasting effects of urokinase and tissue-type plasminogen activators on neointima formation and vessel remodelling after arterial injury.

J Vasc Res 2004 May-Jun;41(3):268-76. Epub 2004 Jun 7.

Molecular Endocrinology Laboratory, Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russia.

Urokinase-type plasminogen activator (uPA) has been implicated in neointima formation and arterial lumen narrowing after angioplasty. To determine the specificity of the action of uPA on vessel remodelling after arterial injury we compared the effects of the recombinant urokinase- and tissue-type plasminogen activators on vessel morphology, cell migration and proliferation. We used a standard model of the balloon catheter injury of the rat carotid artery followed by the periadventitial application to the injured vessel of the one of the recombinant PAs or recombinant alpha(2)-antiplasmin (alpha-AP) in pluronic gel with further immunohistochemistry and morphometry. The perivascular application of alpha-AP immediately after injury attenuated the healing response, significantly reducing neointima size and neointimal SMC numbers. The periadventitial application to the injured artery of recombinant uPA stimulated neointima formation as well as cell proliferation and migration in vivo and induced greater reductions in lumen size than injury alone. In contrast, recombinant tissue-type plasminogen activator reduced the number of neointimal smooth muscle cells and the neointimal area and increased both the lumen area and the area encompassed by the external elastic laminae after balloon catheter injury of the rat carotid artery. In the meantime both PAs nearly doubled medial and adventitial SMC numbers in the vessels. We conclude that the ability to stimulate neointima formation and inward arterial remodelling is a specific property for urokinase plasminogen activator that could not be mimicked by tissue-type plasminogen activator.
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http://dx.doi.org/10.1159/000078825DOI Listing
July 2004
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