Search results for "Plasminogen"
showing 10 items of 142 documents
Enzymatic modification of low-density lipoprotein in the arterial wall: a new role for plasmin and matrix metalloproteinases in atherogenesis.
2004
Objective— Functionally interactive proteases of the plasminogen/plasmin and the matrix metalloproteinase (MMP) system degrade and reorganize the extracellular matrix of the vessel wall in atherosclerosis. Here we investigated whether such proteases are able to confer atherogenic properties onto low density lipoprotein by nonoxidative modification. Methods and Results— Similar to the recently described enzymatically-modified low-density lipoprotein (E-LDL), native LDL exposed to plasmin or matrix MMP-2 or MMP-9 and cholesterylester-hydrolase (CEH) showed extensive deesterification, with ratios of free cholesterol to total cholesterol rising to 0.8 compared with 0.2 in native LDL. When the …
Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells
2016
Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated the crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify coagulation factor XII (FXII), the initiator of the intrinsic coagulation cascade and the kallikrein–kinin system, as a specific immune cell modulator. High levels of FXII activity are present in the plasma of MS patients during relapse. Deficiency or pharmacologic blockade of FXII renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by reduced numbers of interleukin-17A-producing T cells.…
Hereditary angioedema with a mutation in the plasminogen gene
2017
Background Hereditary angioedema (HAE) with normal C1-INH (HAEnCI) may be linked to specific mutations in the coagulation factor 12 (FXII) gene (HAE-FXII) or functional mutations in other genes that are still unknown. We sought to identify and characterize a hitherto unknown type of HAE with normal C1-INH and without mutation in the F12 gene. Methods The study comprised analysis of whole-exome sequencing, Sanger sequencing, and clinical data of patients. Results We detected a mutation in the plasminogen (PLG) gene in patients with HAEnCI. The mutation c.9886A>G was located in exon 9 leading to the missense mutation p.Lys330Glu (K330E) in the kringle 3 domain of the PLG protein. The mutation…
Prognostic value of soluble urokinase plasminogen activator receptor in patients presenting to the emergency department with chest pain suggestive of…
2021
International audience; INTRODUCTION: Soluble urokinase plasminogen activator receptor (suPAR) is a prognostic biomarker of cardiovascular disease. OBJECTIVES: We aimed to evaluate the early prognostic value of suPAR in patients presenting to the emergency department (ED) with chest pain suggestive of acute coronary syndrome (ACS). PATIENTS AND METHODS: In a post-hoc analysis from a multicenter study including patients with a chest pain < 6 h, suPAR concentrations at ED admission were studied according to the outcome at 30-days. RESULTS: 198 patients (median age 56 years) in whom 16% had an ACS, were included. Fifteen (7.3%) patients presented a 30-day event. At ED admission, median (IQR…
Hereditary angioedema in a single family with specific mutations in both plasminogen and SERPING1 genes
2019
BACKGROUND Hereditary angioedema (HAE) is a group of genetic diseases characterized by recurrent, painful and potentially lethal tissue swelling. The most common form results from mutations in the SERPING1 gene, leading to reduced function of complement 1 inhibitor (C1-INH). Rarer forms with normal C1-INH may arise from mutations in the coagulation factor F12 gene, but mostly the genetic background is unknown. Recently, a novel HAE mutation in the plasminogen (PLG) gene was shown. PATIENTS AND METHODS We analyzed the various clinical manifestations of HAE in 14 related patients using clinical data, biochemical analysis for C1-INH and C4 as well as gene sequencing. RESULTS Patients' symptoms…
PAI-1 plasma levels in a general population without clinical evidence of atherosclerosis: relation to environmental and genetic determinants.
1998
Abstract —Plasminogen activator inhibitor-1 (PAI-1) plasma levels have been consistently related to a polymorphism (4G/5G) of the PAI-1 gene. The renin-angiotensin pathway plays a role in the regulation of PAI-1 plasma levels. An insertion ( I )/deletion ( D ) polymorphism of the angiotensin-converting enzyme (ACE) gene has been related to plasma and cellular ACE levels. In 1032 employees (446 men and 586 women; 22 to 66 years old) of a hospital in southern Italy, we investigated the association between PAI-1 4G/5G and the ACE I/D gene variants and plasma PAI-1 antigen levels. None of the individuals enrolled had clinical evidence of atherosclerosis. In univariate analysis, PAI-1 levels we…
Kallikrein–kinin system and fibrinolysis in hereditary angioedema due to factor XII gene mutation Thr309Lys
2009
In a subgroup of hereditary angioedema (HAE) patients with normal C1-esterase inhibitor levels, HAE is caused by a Thr309Lys mutation in the coagulation factor XII (F12) gene. The aim of this study was to examine elements of the kallikrein-kinin system ('contact system') and the downstream-linked coagulation, complement and fibrinolytic systems in the plasma of six patients with HAE caused by the Thr309Lys mutation and healthy probands. Blood samples were taken from participants during the symptom-free interval between attacks. Samples were analyzed for activity and concentrations of components of the kallikrein-kinin system and linked enzyme systems. The mean FXII clotting activity was 90%…
Increased plasminogen activator inhibitor antigen levels in diabetic patients with stable angina
1991
PAI-1 antigen, tPA antigen and thrombin - antithrombin III complexes (TAT) levels were measured in 10 males with stable angina and type-II diabetes mellitus and in 16 males with stable angina without diabetes or other risk factors (hyperfibrinogenaemia, hyperlipidaemia, diabetes, hypertension, smoking and obesity) known to increase PAI levels. Ten healthy men of equivalent age served as controls. Because only diabetics with coronary artery disease (CAD) showed a decreased fibrinolytic capacity, a second study was performed on the 16 non-diabetic CAD patients to determine whether submaximal workload induces significant changes of tPA and PAI levels. TAT levels were increased in CAD, and sign…
The PAI-1 gene locus 4G/5G polymorphism is associated with a family history of coronary artery disease.
1998
Abstract —A family history of ischemic events is a major determinant of coronary artery disease (CAD). Plasma levels of plasminogen activator inhibitor 1 (PAI-1) modulate this risk. A deletion/insertion polymorphism within the PAI-1 locus (4G/5G) affects the expression of this gene. We investigated the relationship between the PAI-1 4G/5G polymorphism in 1179 healthy employees of our institution and the occurrence of CAD in their first-degree relatives. A family history of documented ischemic coronary disease was assessed by a modified WHO questionnaire. The PAI-1 4G/5G polymorphism was evaluated by polymerase chain reaction and endonuclease digestion. The group with a first-degree relativ…
Hereditary angioedema with normal C1-INH withversuswithout specificF12gene mutations
2015
Background Hereditary angioedema with normal C1-INH may be linked to specific mutations in the coagulation factor 12 (FXII) gene (HAE-FXII) or mutations in genes that are still unknown (HAE-unknown). To assess the differences in transmission and inheritance, clinical features, and laboratory parameters between patients with HAE-FXII and HAE-unknown. Methods Sixty-nine patients with HAE-FXII from 23 unrelated families and 196 patients with HAE-unknown from 65 unrelated families were studied. Results Both HAE-FXII and HAE-unknown are inherited as autosomal-dominant traits with incomplete penetrance. The male to female ratio was 1 : 68 in HAE-FXII and 1 : 6.3 in HAE-unknown. The maternal to pa…