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https://www.readbyqxmd.com/read/27783862/adipose-tissue-derived-plasminogen-activator-inhibitor-1-function-and-regulation
#1
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
#2
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...
October 3, 2016: 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
#3
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
#4
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
#5
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
#6
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...
May 10, 2016: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/26440573/abdominal-aortic-aneurysms-and-diabetes-mellitus
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/25723058/diabetic-retinopathy-could-the-alpha-1-antitrypsin-be-a-therapeutic-option
#13
REVIEW
Gustavo Ortiz, Juan P Salica, Eduardo H Chuluyan, Juan E Gallo
Diabetic retinopathy is one of the most important causes of blindness. The underlying mechanisms of this disease include inflammatory changes and remodeling processes of the extracellular-matrix (ECM) leading to pericyte and vascular endothelial cell damage that affects the retinal circulation. In turn, this causes hypoxia leading to release of vascular endothelial growth factor (VEGF) to induce the angiogenesis process. Alpha-1 antitrypsin (AAT) is the most important circulating inhibitor of serine proteases (SERPIN)...
2014: Biological Research
https://www.readbyqxmd.com/read/25609736/diabetic-nephropathy-is-associated-with-increased-urine-excretion-of-proteases-plasmin-prostasin-and-urokinase-and-activation-of-amiloride-sensitive-current-in-collecting-duct-cells
#14
Henrik Andersen, Ulla G Friis, Pernille B L Hansen, Per Svenningsen, Jan Erik Henriksen, Boye L Jensen
BACKGROUND: Diabetic nephropathy (DN) is associated with hypertension, expanded extracellular volume and impaired renal Na(+) excretion. It was hypothesized that aberrant glomerular filtration of serine proteases in DN causes proteolytic activation of the epithelial sodium channel (ENaC) in the kidney by excision of an inhibitory peptide tract from the γ subunit. METHODS: In a cross-sectional design, urine, plasma and clinical data were collected from type 1 diabetic patients with DN (n = 19) and matched normoalbuminuric type 1 diabetics (controls, n = 20)...
May 2015: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/25492830/amiloride-lowers-blood-pressure-and-attenuates-urine-plasminogen-activation-in-patients-with-treatment-resistant-hypertension
#15
RANDOMIZED CONTROLLED TRIAL
Christina S Oxlund, Kristian B Buhl, Ib A Jacobsen, Mie R Hansen, Jeppe Gram, Jan Erik Henriksen, Karoline Schousboe, Lise Tarnow, Boye L Jensen
In conditions with albuminuria, plasminogen is aberrantly filtered across the glomerular barrier and activated along the tubular system to plasmin. In the collecting duct, plasmin activates epithelial sodium channels (ENaC) proteolytically. Hyperactivity of ENaC could link microalbuminuria/proteinuria to resistant hypertension. Amiloride, an ENaC inhibitor, inhibits urokinase-type plasminogen activator. We hypothesized that amiloride (1) reduces blood pressure (BP); (2) attenuates plasminogen-to-plasmin activation; and (3) inhibits urine urokinase-type plasminogen activator in patients with resistant hypertension and type 2 diabetes mellitus (T2DM)...
December 2014: Journal of the American Society of Hypertension: JASH
https://www.readbyqxmd.com/read/25482671/urinary-serine-proteases-and-activation-of-enac-in-kidney-implications-for-physiological-renal-salt-handling-and-hypertensive-disorders-with-albuminuria
#16
REVIEW
Per Svenningsen, Henrik Andersen, Lise H Nielsen, Boye L Jensen
Serine proteases, both soluble and cell-attached, can activate the epithelial sodium channel (ENaC) proteolytically through release of a putative 43-mer inhibitory tract from the ectodomain of the γ-subunit. ENaC controls renal Na(+) excretion and loss-of-function mutations lead to low blood pressure, while gain-of-function mutations lead to impaired Na(+) excretion, hypertension, and hypokalemia. We review an emerging pathophysiological concept that aberrant glomerular filtration of plasma proteases, e.g...
March 2015: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/25411467/inhibition-of-thrombin-activated-fibrinolysis-inhibitor-increases-survival-in-experimental-kidney-fibrosis
#17
John M Atkinson, Nick Pullen, Michelle Da Silva-Lodge, Lynne Williams, Tim S Johnson
Uncontrolled diabetes, inflammation, and hypertension are key contributors to progressive renal fibrosis and subsequent loss of renal function. Reduced fibrinolysis appears to be a feature of ESRD, but its contribution to the fibrotic program has not been extensively studied. Here, we show that in patients with CKD, the activity levels of serum thrombin-activated fibrinolysis inhibitor and plasmin strongly correlated with the degree of renal function impairment. We made similar observations in rats after subtotal nephrectomy and tested whether pharmacologic inhibition of thrombin-activated fibrinolysis inhibitor with UK-396082 could reduce renal fibrosis and improve renal function...
August 2015: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/25380887/ykl-40-a-marker-of-cardiovascular-disease-and-endothelial-dysfunction-in-kidney-transplant-recipients
#18
Jolanta Malyszko, E Koc-Zorawska, Jacek Malyszko
BACKGROUND: YKL-40 is an inflammatory glycoprotein involved in endothelial dysfunction and expressed in macrophages in the earliest lesion of atherosclerosis. Because cardiovascular mortality is the main cause of death, there are no data on kidney transplant recipients, so the aim of the study was to assess YKL-40 in that population, with particular attention being paid to the relationship with endothelial damage. METHODS: We studied 68 patients after kidney transplantation...
October 2014: Transplantation Proceedings
https://www.readbyqxmd.com/read/24818165/evaluation-of-serum-fibrinogen-plasminogen-%C3%AE-2-anti-plasmin-and-plasminogen-activator-inhibitor-levels-pai-and-their-correlation-with-presence-of-retinopathy-in-patients-with-type-1-dm
#19
COMPARATIVE STUDY
Sefika Burcak Polat, Nagihan Ugurlu, Fatma Yulek, Huseyin Simavli, Reyhan Ersoy, Bekir Cakir, Ozcan Erel
BACKGROUND. Diabetic retinopathy (DR) is the leading cause of blindness in the world. Retinopathy can still progress despite optimal metabolic control. The aim of the study was to determine whether different degrees of DR (proliferative or nonproliferative) were associated with abnormally modulated hemostatic parameters in patients with T1DM. METHOD. 52 T1DM patients and 40 healthy controls were enrolled in the study. Patients were subdivided into three categories. Group I was defined as those without retinopathy, group II with NPRP, and group III with PRP...
2014: Journal of Diabetes Research
https://www.readbyqxmd.com/read/24805959/plasmin-in-urine-from-patients-with-type-2-diabetes-and-treatment-resistant-hypertension-activates-enac-in-vitro
#20
Kristian B Buhl, Christina S Oxlund, Ulla G Friis, Per Svenningsen, Claus Bistrup, Ib A Jacobsen, Boye L Jensen
BACKGROUND: Aberrant filtration of plasminogen from plasma and subsequent activation to plasmin in the urinary space may activate proteolytically the epithelial sodium channel, ENaC. In conditions with chronic albuminuria, this may cause hypertension. It was hypothesized that patients with type 2 diabetes mellitus (T2DM) and treatment-resistant hypertension excrete plasmin(ogen) in urine in proportion to albumin and that plasmin confers to urine the ability to activate ENaC. METHOD: Patients (n = 113) with T2DM and resistant hypertension, defined as systolic blood pressure (SBP) more than 130 mmHg and/or diastolic blood pressure (DBP) more than 80 mmHg despite use of at least three drugs with one diuretic and one renin-angiotensin system inhibitor, were included...
August 2014: Journal of Hypertension
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