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Plasmin diabetic

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https://www.readbyqxmd.com/read/29114573/plasmin-reduces-fibronectin-deposition-by-mesangial-cells-in-a-protease-activated-receptor-1-independent-manner
#1
Maaike Waasdorp, JanWillem Duitman, C Arnold Spek
Background: Protease-activated receptor-1 (PAR-1) potentiates diabetic nephropathy (DN) as evident from reduced kidney injury in diabetic PAR-1 deficient mice. Although thrombin is the prototypical PAR-1 agonist, anticoagulant treatment does not limit DN in experimental animal models suggesting that thrombin is not the endogenous PAR-1 agonist driving DN. Objectives: To identify the endogenous PAR-1 agonist potentiating diabetes-induced nephropathy. Methods: Unbiased protease expression profiling in glomeruli from human kidneys with DN was performed using publically available microarray data...
July 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29075072/evaluation-of-coagulation-profile-in-children-with-type-1-diabetes-mellitus-using-rotational-thromboelastometry
#2
Cigdem Binay, Ayse Bozkurt Turhan, Enver Simsek, Ozcan Bor, Olga Meltem Akay
The prothrombotic state in type 1 diabetes mellitus (T1DM) has been reported as a plausible cause of vascular complications. Rotational thromboelastometry (ROTEM) assay enables the global assessment of coagulation status. This study aimed to assess hypercoagulability in children with T1DM using ROTEM. A total of 43 T1DM children (20 females and 23 males) aged 2-18 years and age- and sex-matched 30 healthy control subjects were enrolled in the study group. ROTEM assays [intrinsic TEM (INTEM) and extrinsic TEM (EXTEM)] were used to measure and analyze coagulation time (CT), clot formation time, maximum clot firmness (MCF)...
December 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28890943/trial-of-amiloride-in-type-2-diabetes-with-proteinuria
#3
Mark L Unruh, V Shane Pankratz, John E Demko, Evan C Ray, Rebecca P Hughey, Thomas R Kleyman
INTRODUCTION: Renal Na(+) retention and extracellular fluid volume expansion are hallmarks of nephrotic syndrome, which occurs even in the absence of activation of hormones that stimulate renal Na(+) transporters. Plasmin-dependent activation of the epithelial Na(+) channel (ENaC) has been proposed to have a role in renal Na(+) retention in the setting of nephrotic syndrome. We hypothesized that the ENaC inhibitor amiloride would be an effective therapeutic agent in inducing a natriuresis and lowering blood pressure in individuals with macroscopic proteinuria...
September 2017: KI Reports
https://www.readbyqxmd.com/read/28747040/glycative-and-oxidative-stress-are-associated-with-altered-thrombus-composition-in-diabetic-patients-with-st-elevation-myocardial-infarction
#4
Antonia Sambola, Marisol Ruiz-Meana, Ignasi Barba, Bruno García Del Blanco, José A Barrabés, G Y Lip, Úrsula Vilardosa, Sara Sansaloni, Pau Rello, David García-Dorado
BACKGROUND: The role of type 2 diabetes (T2DM) on composition of thrombus has not been fully characterized in patients with ST-elevation myocardial infarction (STEMI). AIMS: To elucidate the differences between diabetic and non-diabetic patients with STEMI in relation to the composition of coronary thrombus, and the potential association of these differences with glycated haemoglobin levels and markers of oxidative stress. METHODS: Intracoronary thrombi from consecutive thrombus aspiration procedures in STEMI patients, 25 diabetic and 28 non-diabetic, were analyzed by immunofluorescence with confocal microscopy...
September 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28710283/amorphous-protein-aggregates-stimulate-plasminogen-activation-leading-to-release-of-cytotoxic-fragments-that-are-clients-for-extracellular-chaperones
#5
COMPARATIVE STUDY
Patrick Constantinescu, Rebecca A Brown, Amy R Wyatt, Marie Ranson, Mark R Wilson
The misfolding of proteins and their accumulation in extracellular tissue compartments as insoluble amyloid or amorphous protein aggregates are a hallmark feature of many debilitating protein deposition diseases such as Alzheimer's disease, prion diseases, and type II diabetes. The plasminogen activation system is best known as an extracellular fibrinolytic system but was previously reported to also be capable of degrading amyloid fibrils. Here we show that amorphous protein aggregates interact with tissue-type plasminogen activator and plasminogen, via an exposed lysine-dependent mechanism, to efficiently generate plasmin...
September 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28612231/epsilon-aminocaproic-acid-prevents-high-glucose-and-insulin-induced-invasiveness-in-mda-mb-231-breast-cancer-cells-modulating-the-plasminogen-activator-system
#6
Rubí Viedma-Rodríguez, María Guadalupe Martínez-Hernández, Luis Antonio Flores-López, Luis Arturo Baiza-Gutman
Obesity and type II diabetes mellitus have contributed to the increase of breast cancer incidence worldwide. High glucose concentration promotes the proliferation of metastatic cells, favoring the activation of the plasminogen/plasmin system, thus contributing to tumor progression. The efficient formation of plasmin is dependent on the binding of plasminogen to the cell surface. We studied the effect of ε-aminocaproic acid (EACA), an inhibitor of the binding of plasminogen to cell surface, on proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and plasminogen activation system, in metastatic MDA-MB-231 breast cancer cells grown in a high glucose microenvironment and treated with insulin...
June 13, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28427074/enzymatic-vitreolysis-for-vitreomacular-traction-in-diabetic-retinopathy
#7
REVIEW
Stanislao Rizzo, Daniela Bacherini
Vitreomacular traction (VMT) is one of many possible factors involved in the etiology of diabetic macular edema (DME). Pharmacologic vitreoretinal separation is a potential alternative to vitrectomy for VMT in diabetic retinopathy. Small case series have been published on the use of enzymatic vitreolysis in tractional DME, and demonstrate that the enzymatic release of the posterior vitreous cortex is more likely following the injection of plasmin enzyme. Further prospective and randomized clinical trials are necessary to evaluate the clinical relevance of ocriplasmin for vitreomacular traction in diabetic retinopathy, and additional studies are needed to determine more accurately which patients might benefit most from this treatment and how often and at what concentration ocriplasmin should be administered...
2017: Developments in Ophthalmology
https://www.readbyqxmd.com/read/28266313/development-of-a-plasminogen-activator-inhibitor-pai-1-assay-and-comparison-of-plasma-pai-1-activity-in-hyperlipidemic-dyslipidemic-dogs-with-either-hyperadrenocorticism-or-diabetes-mellitus-and-healthy-dogs
#8
Cheryl J Wong, Michael Koch, Erica L Behling-Kelly
Thrombosis is a serious complication of many canine diseases and may be related to decreased fibrinolytic potential. Plasminogen activator inhibitor-1 (PAI-1) is the key regulator of fibrinolysis with increased levels demonstrated in states of pro-thrombosis and abnormal lipid metabolism. Our objective was to develop and validate a canine PAI-1 activity assay and test whether dogs with hyperadrenocorticism or diabetes mellitus that are hyperlipidemic/dyslipidemic have increased plasma PAI-1 activity. Functionally active PAI-1 in the plasma sample was incubated with recombinant tissue plasminogen activator (tPA), allowing the formation of a 1:1 stoichiometric inactive complex...
April 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/27783862/adipose-tissue-derived-plasminogen-activator-inhibitor-1-function-and-regulation
#9
Hiroshi Kaji
Adipose tissue has recently been reevaluated as an endocrine organ, and adipose-tissue-derived endocrine factors are termed adipokines. Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of PAs, which convert plasminogen into plasmin, a critical protease involved in fibrinolysis. PAI-1 induces fibrinogenesis by suppressing intravascular and tissue fibrinolysis. Moreover, PAI-1 exerts various cellular effects independently of fibrinolysis. Although PAI-1 is expressed in various tissues, its expression is regulated by numerous growth factors, cytokines, and hormones in a paracrine and endocrine manner...
September 15, 2016: Comprehensive Physiology
https://www.readbyqxmd.com/read/27696935/the-evolution-of-recombinant-thrombolytics-current-status-and-future-directions
#10
Yogender Pal Khasa
Cardiovascular disorders are on the rise worldwide due to alcohol abuse, obesity, hypertension, raised blood lipids, diabetes and age-related risks. The use of classical antiplatelet and anticoagulant therapies combined with surgical intervention helped to clear blood clots during the inceptive years. However, the discovery of streptokinase and urokinase ushered the way of using these enzymes as thrombolytic agents to degrade the fibrin network with an issue of systemic hemorrhage. The development of second generation plasminogen activators like anistreplase and tissue plasminogen activator partially controlled this problem...
July 4, 2017: Bioengineered
https://www.readbyqxmd.com/read/27511457/an-additive-effect-of-anti-pai-1-antibody-to-ace-inhibitor-on-slowing-the-progression-of-diabetic-kidney-disease
#11
Chunyan Gu, Jiandong Zhang, Nancy A Noble, Xiao-Rong Peng, Yufeng Huang
While angiotensin II blockade slows the progression of diabetic nephropathy, current data suggest that it alone cannot stop the disease process. New therapies or drug combinations will be required to further slow or halt disease progression. Inhibition of plasminogen activator inhibitor type 1 (PAI-1) aimed at enhancing ECM degradation has shown therapeutic potential in diabetic nephropathy. Here, using a mouse model of type diabetes, the maximally therapeutic dose of the PAI-1-neutralizing mouse monoclonal antibody (MEDI-579) was determined and compared with the maximally effective dose of enalapril...
November 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27258009/novel-plasminogen-activator-inhibitor-1-inhibitors-prevent-diabetic-kidney-injury-in-a-mouse-model
#12
Bo Yeong Jeong, Md Jamal Uddin, Jong Hee Park, Jung Hwa Lee, Hi Bahl Lee, Toshio Miyata, Hunjoo Ha
Diabetic nephropathy is the leading cause of end-stage renal disease worldwide, but no effective therapeutic strategy is available. Because plasminogen activator inhibitor-1 (PAI-1) is increasingly recognized as a key factor in extracellular matrix (ECM) accumulation in diabetic nephropathy, this study examined the renoprotective effects of TM5275 and TM5441, two novel orally active PAI-1 inhibitors that do not trigger bleeding episodes, in streptozotocin (STZ)-induced diabetic mice. TM5275 (50 mg/kg) and TM5441 (10 mg/kg) were administered orally for 16 weeks to STZ-induced diabetic and age-matched control mice...
2016: PloS One
https://www.readbyqxmd.com/read/27214087/significant-natriuretic-and-antihypertensive-action-of-the-epithelial-sodium-channel-blocker-amiloride-in-diabetic-patients-with-and-without-nephropathy
#13
Henrik Andersen, Pernille B L Hansen, Claus Bistrup, Flemming Nielsen, Jan Erik Henriksen, Boye L Jensen
OBJECTIVE: Diabetic nephropathy is associated with aberrant glomerular filtration of serine proteases. The study was designed to test the hypothesis that the epithelial sodium channel is activated proteolytically by urine plasmin in diabetic nephropathy and mediates renal sodium retention. METHODS: In an open-label intervention study on type 1 diabetes patients on standardized NaCl intake (200 mmol/day) with (n = 15) and without diabetic nephropathy (control, n = 12), urinary Na excretion in response to oral amiloride (20 or 40 mg/day for 2 days) was compared...
August 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27167858/impaired-plasma-clot-lysis-and-its-determinants-in-patients-with-obstructive-sleep-apnea-syndrome
#14
Anna Borratynska, Katarzyna Stopyra-Pach, Korneliusz Fil, Anetta Undas
Evidence indicates that hypercoagulability and impaired fibrinolysis have been observed in patients with obstructive sleep apnea syndrome (OSAS). It is unclear which factors determine prolonged fibrin clot lysis in OSAS. One hundred and sixty-five consecutive patients suspected of OSAS underwent overnight polysomnography. Prior to polysomnography, we determined plasma clot lysis time (CLT), plasminogen activator inhibitor (PAI)-1 antigen, activated thrombin-activatable fibrinolysis inhibitor (TAFIa), plasmin, and antiplasmin...
December 2016: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/26440573/abdominal-aortic-aneurysms-and-diabetes-mellitus
#15
REVIEW
Kalliopi Pafili, Ioanna Gouni-Berthold, Nikolaos Papanas, Dimitri P Mikhailidis
There is accumulating evidence that risk profiles differ between coronary artery disease and abdominal aortic aneurysms (AAAs). However, diabetes mellitus (DM) appears to be negatively associated with AAA formation. The underlying mechanisms for this negative relationship are far from defined, but may include: increased arterial wall matrix formation via advanced glycation end products; suppression of plasmin and reduction of levels and activity of matrix metalloproteinases (MMP)-2 and 9; diminished aortic wall macrophage infiltration, elastolysis and neovascularization...
November 2015: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/26330668/the-biology-of-annexin-a2-from-vascular-fibrinolysis-to-innate-immunity
#16
Katherine A Hajjar
Annexin A2 is a multicompartmental protein that orchestrates a spectrum of dynamic membrane-related events. At cell surfaces, A2 forms the (A2•S100A10)2 complex which accelerates tissue plasminogen activator-dependent activation of the fibrinolytic protease, plasmin. Anti-A2 antibodies are associated with clinical thrombosis in antiphospholipid syndrome, whereas overexpression of A2 promotes hyperfibrinolytic bleeding in acute promyelocytic leukemia. A2 is upregulated in hypoxic tissues, and mice deficient in A2 are resistant to hypoxia-related retinal neovascularization in a model of diabetic retinopathy...
2015: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/25991438/promotion-of-wound-healing-by-an-agonist-of-adenosine-a2a-receptor-is-dependent-on-tissue-plasminogen-activator
#17
M Carmen Montesinos, Avani Desai-Merchant, Bruce N Cronstein
Impaired wound healing, as it occurs in diabetes mellitus or long-term corticoid treatment, is commonly associated with disability, diminished quality of life, and high economic costs. Selective agonists of the A2A receptor subtype of adenosine, an endogenous regulator of inflammation, promote tissue repair in animal models, both healthy and with impaired healing. Plasmin-mediated proteolysis of fibrin and other matrix proteins is essential for cell migration at sites of injury. Since adenosine A2A receptor activation increases plasminogen activator release from macrophages and mast cells, we studied the effect of a selective agonist, CGS-21680, on full-thickness excisional wound closure in wild-type, urokinase plasminogen activator (uPA)-deficient, and tissue plasminogen activator (tPA)-deficient mice...
December 2015: Inflammation
https://www.readbyqxmd.com/read/25843697/treatment-of-vitreomacular-traction-syndrome-with-autologous-plasmin-enzyme
#18
F J Rodríguez-Hurtado, M P Garrido Collado, V César Delgado Ceballos
PURPOSE: To determine whether intravitreal injection of autologous plasmin enzyme (APE) is effective in vitreomacular traction syndrome (VMTS) by improving visual acuity and restoring macular morphology. METHODS: A prospective study of 11 consecutive patients diagnosed with VMTS in the Ophthalmology Department from January to May, 2011. INCLUSION CRITERIA: best corrected visual acuity (BCVA) less than 0.5, and vitreomacular attachment in foveal area resulting in macular thickness>250 microns diagnosed by optical coherence tomography (Cirrus OCT, Carl Zeiss Meditec, Inc, Oberkochen, Germany)...
June 2015: Archivos de la Sociedad Española de Oftalmología
https://www.readbyqxmd.com/read/25812991/pharmacologic-vitreolysis-with-ocriplasmin-rationale-for-use-and-therapeutic-potential-in-vitreo-retinal-disorders
#19
Matin Khoshnevis, J Sebag
With increased knowledge about the origins and pathophysiology of vitreo-retinal disorders—and, in particular, the central role of anomalous posterior vitreous detachment in vitreo-maculopathies—a paradigm shift from surgery to pharmacotherapy is taking place with the development of pharmacologic vitreolysis. The first approved agent for pharmacologic vitreolysis therapy is ocriplasmin, a truncated form of the nonspecific serine protease plasmin. Twelve studies comprise the current ocriplasmin clinical trial program, demonstrating the efficacy and safety of a single intravitreal injection of ocriplasmin for the treatment of patients with symptomatic vitreo-macular adhesion or vitreo-macular traction, including patients with macular holes...
April 2015: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/25762598/-role-of-angiostatins-in-diabetic-complications
#20
REVIEW
A A Tykhomyrov, S I Shram, T V Grinenko
Angiogenesis is a process through which new blood vessels form from pre-existing vessels. Angiogenesis is regulated by a number of factors of peptide nature. Disbalance of angiogenic system appears to be the major causative factor contributing vascular abnormalities in diabetes mellitus, resulting in various complications. Angiostatins, which are kringle-containing fragments of plasminogen/plasmin, are known to be powerful physiological inhibitors of neovascularization. In the present review, current literature data on peculiarities of production of angiostatins and their functioning at diabetes mellitus are summarized and analyzed for the first time...
January 2015: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
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