Antibiotics, Biocides, Residues and Resistance Unit, Fougères Laboratory, French Agency for Food, Environmental and Occupational Health & Safety (ANSES), Fougères, France.
Antibiotics, Biocides, Residues and Resistance Unit, Fougères Laboratory, French Agency for Food, Environmental and Occupational Health & Safety (ANSES), Fougères, France.
Antibiotics, Biocides, Residues and Resistance Unit, Fougères Laboratory, French Agency for Food, Environmental and Occupational Health & Safety (ANSES), Fougères, France.
Département de Biochimie et Médecine Moléculaire, and CRCHUM-Faculté de Médecine, Université de Montréal, Montreal, QC, Canada. g.ferbeyre@umontreal.ca.
Département de Chimie-Faculté des Arts et des Sciences, Université de Montréal, 2900 Edouard Montpetit, Succursale Centre-Ville, CP 6128, Montreal, QC, H3C3J7, Canada. ar.schmitzer@umontreal.ca.
Background High plasma prekallikrein was reported to be associated with increased risks of stroke, but the causality for these associations remains unclear. We aimed to investigate the associations of...
We examined how prekallikrein (PK) activation on human microvascular endothelial cells (HMVECs) is regulated by the ambient concentration of C1 inhibitor (C1INH) and prolylcarboxypeptidase (PRCP)....
We sought to examine the specificity of PK activation on HMVECs by PRCP and the role of C1INH to regulate it, high-molecular-weight kininogen (HK) cleavage, and bradykinin (BK) liberation....
Investigations were performed on cultured HMVECs. Immunofluorescence, enzymatic activity assays, immunoblots, small interfering RNA knockdowns, and cell transfections were used to perform these studie...
Cultured HMVECs constitutively coexpressed PK, HK, C1INH, and PRCP. PK activation on HMVECs was modulated by the ambient C1INH concentration. In the absence of C1INH, forming PKa on HMVECs cleaved 120...
These combined studies indicated that on HMVECs, PK activation and HK cleavage to liberate BK were modulated by the local concentrations of C1INH and PRCP....
Recent evidence has revealed that circulating coagulation factor prekallikrein (PK), an important part of the kallikrein-kinin system, regulates cholesterol metabolism, but the association between ser...
This cross-sectional study included 256 subjects (aged from 1 month to 90 years) who underwent physical examinations at the First People's Hospital of Huaihua, China. After overnight fasting, serum wa...
The median serum PK level was 280.9 µg/mL (IQR 168.0, 377.0), and this level changed with age but not sex. The serum PK level was positively correlated with the serum total cholesterol (TC), low-densi...
Elevated serum PK levels were significantly associated with the likelihood of hypercholesterolemia and hypertriglyceridemia, and the possible threshold values of PK levels were 344.9 µg/mL and 305.70 ...
High-molecular weight kininogen (HK) circulates in plasma as a complex with zymogen prekallikrein (PK). HK is both a substrate and a cofactor for activated plasma kallikrein, and the principal exosite...
To determine the structure of the complex formed between PK apple domains and an HKD6 fragment and compare this with the coagulation factor XI (FXI)-HK complex....
We produced recombinant FXI and PK heavy chains (HCs) spanning all 4 apple domains. We cocrystallized PKHC (and subsequently FXIHC) with a 31-amino acid synthetic peptide spanning HK residues Ser565-L...
The 2.3Å PKHC-HK peptide crystal structure revealed that the HKD6 sequence WIPDIQ (Trp569-Gln574) binds to the apple 1 domain and HK FNPISDFPDT (Phe582-Thr591) binds to the apple 2 domain with a flexi...
The alternate conformations and exosite binding of the HKD6 peptide likely reflects the diverging relationship of HK to the functions of PK and FXI....
Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent edema and predominantly caused by the dysregulation of the kinin-kallikrein system....
This manuscript presents the results of preclinical and early clinical trials of newer drugs targeting the dysregulated kinin-kallikrein system. ATN-249 is an oral drug that has shown promising result...
The targeted treatment of the dysregulated kinin-kallikrein system with specific inhibitors is promising for the prevention of angioedema attacks. Ongoing phase III studies will provide further insigh...
Severe high-molecular-weight kininogen (HK) deficiency is a poorly studied autosomal recessive contact system defect caused by pathogenic, biallelic KNG1 variants....
We performed the first comprehensive analysis of diagnostic, clinical, genetic, and epidemiological aspects of HK deficiency....
We collected clinical information and blood samples from a newly detected HK-deficient individual and from published cases identified by a systematic literature review. Activity and antigen levels of ...
We identified 48 cases of severe HK deficiency (41 families), of these 47 have been previously published (n = 19 from gray literature). We genotyped 3 cases and critically appraised 10 studies with ge...
HK deficiency is a rare condition with only few known pathogenic variants. It has an apparently good prognosis but is prone to misdiagnosis. Our understanding of its clinical implications is still lim...
Prolylcarboxypeptidase (PRCP, PCP, Lysosomal Pro-X-carboxypeptidase, Angiotensinase C) controls angiotensin- and kinin-induced cell signaling. Elevation of PRCP appears to be activated in chronic infl...
Human serum albumin (HSA) is the most abundant plasma protein and is sensitive to glycation in vivo. The chronic hyperglycemic conditions in patients with diabetes mellitus (DM) induce a nonenzymatic ...
This study aimed to determine the relevance of HSA-AGE toward diabetic pathophysiology....
The plasma obtained from patients with DM and euglycemic volunteers was probed for activation of FXII, prekallikrein (PK), and cleaved high-molecular-weight kininogen by immunoblotting. Constitutive p...
Plasma obtained from patients with DM contained increased plasma AGEs, activated FXIIa, and resultant cleaved cleaved high-molecular-weight kininogen. Elevated constitutive plasma kallikrein enzymatic...
These data indicate a proinflammatory role of HSA-AGEs in the pathophysiology of DM via FXII and kallikrein-kinin system activation. A procoagulant effect of FXII activation was lost through the inhib...
Titanium (Ti) and its alloys are widely used in manufacturing medical devices because of their strength and resistance to corrosion. Although Ti compounds are considered compatible with blood, they ap...
The objective of this study was to compare Ti and titanium nitride (TiN) with known activators of contact activation (kaolin and silica) in plasma-clotting assays and to assess binding and activation ...
Ti-based nanospheres and foils were compared with kaolin, silica, and aluminum in plasma-clotting assays. Binding and activation of FXII, prekallikrein, HK, and FXI to surfaces was assessed with weste...
Using equivalent surface amounts, Ti and TiN were comparable with kaolin and superior to silica, for inducing coagulation and FXII autoactivation. Similar to many inducers of contact activation, Ti an...
Titanium compounds induce contact activation with a potency comparable with that of kaolin. Binding of FXII with Ti shares some features with FXII binding to soluble polyanions but may have unique fea...
Factor XII (FXII), the precursor of the protease FXIIa, contributes to pathologic processes including angioedema and thrombosis. Here, we review recent work on structure-function relationships for FXI...
FXII is a homolog of pro-hepatocyte growth factor activator (Pro-HGFA). We prepared FXII in which domains are replaced by corresponding parts of Pro-HGA, and tested them in FXII activation and activit...
We propose a model in which FXII is normally maintained in a closed conformation resistant to activation by intramolecular interactions involving the fibronectin type-2 and kringle domains. These inte...
