Endothelial cell activation during edematous attacks of hereditary angioedema types i and II

Erika Kajdácsi, Péter K. Jani, Dorottya Csuka, L. Varga, Z. Prohászka, H. Farkas, L. Cervenák

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background Hereditary angioedema (HAE) caused by C1-inhibitor (C1-INH) deficiency (HAE-C1-INH) is a potentially life-threatening rare disease caused by the decreased activity of C1-INH. Lack of C1-INH leads to overproduction of bradykinin, a potent vasoactive peptide. Although angioedema is induced by bradykinin, the function and activation of endothelial cells (ECs), the targets of bradykinin, have not yet been studied during HAE attacks. Objective We studied whether EC function is altered during HAE attacks in comparison with attack-free intervals. Methods Forty-six consecutive samples obtained during attacks from 18 patients with HAE-C1-INH were compared with inter-attack samples of the same patients. The patients' sera were tested for von Willebrand factor (VWF) antigen, VWF collagen-binding activity, soluble E-selectin, and endothelin-1 levels by using ELISA and BRAHMS Kryptor technologies. Results Levels of all 4 EC markers (VWF antigen, VWF collagen-binding activity, soluble E-selectin, and endothelin-1) were significantly increased during HAE attacks. Their increases were even more obvious in the subgroup of patients without any pre-existing risk factors for endothelial dysfunction. Conclusion In this study we demonstrated that ECs are activated during HAE attacks. Our results might suggest the need for revising the knowledge on the pathogenesis of HAE-C1-INH and for reconsidering the role of ECs as a possible novel therapeutic target in patients with this disease.

Original languageEnglish
Pages (from-to)1686-1691
Number of pages6
JournalJournal of Allergy and Clinical Immunology
Volume133
Issue number6
DOIs
Publication statusPublished - 2014

Fingerprint

Hereditary Angioedema Types I and II
Hereditary Angioedemas
Endothelial Cells
von Willebrand Factor
Bradykinin
E-Selectin
Endothelin-1
Collagen
Angioedema
Rare Diseases

Keywords

  • activation
  • attack
  • C1-inhibitor deficiency
  • clinical study
  • endothelial cells
  • endothelin-1
  • Hereditary angioedema
  • soluble E-selectin
  • von Willebrand factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Endothelial cell activation during edematous attacks of hereditary angioedema types i and II. / Kajdácsi, Erika; Jani, Péter K.; Csuka, Dorottya; Varga, L.; Prohászka, Z.; Farkas, H.; Cervenák, L.

In: Journal of Allergy and Clinical Immunology, Vol. 133, No. 6, 2014, p. 1686-1691.

Research output: Contribution to journalArticle

@article{317ca8da0cad4faaaab5a97d5991e835,
title = "Endothelial cell activation during edematous attacks of hereditary angioedema types i and II",
abstract = "Background Hereditary angioedema (HAE) caused by C1-inhibitor (C1-INH) deficiency (HAE-C1-INH) is a potentially life-threatening rare disease caused by the decreased activity of C1-INH. Lack of C1-INH leads to overproduction of bradykinin, a potent vasoactive peptide. Although angioedema is induced by bradykinin, the function and activation of endothelial cells (ECs), the targets of bradykinin, have not yet been studied during HAE attacks. Objective We studied whether EC function is altered during HAE attacks in comparison with attack-free intervals. Methods Forty-six consecutive samples obtained during attacks from 18 patients with HAE-C1-INH were compared with inter-attack samples of the same patients. The patients' sera were tested for von Willebrand factor (VWF) antigen, VWF collagen-binding activity, soluble E-selectin, and endothelin-1 levels by using ELISA and BRAHMS Kryptor technologies. Results Levels of all 4 EC markers (VWF antigen, VWF collagen-binding activity, soluble E-selectin, and endothelin-1) were significantly increased during HAE attacks. Their increases were even more obvious in the subgroup of patients without any pre-existing risk factors for endothelial dysfunction. Conclusion In this study we demonstrated that ECs are activated during HAE attacks. Our results might suggest the need for revising the knowledge on the pathogenesis of HAE-C1-INH and for reconsidering the role of ECs as a possible novel therapeutic target in patients with this disease.",
keywords = "activation, attack, C1-inhibitor deficiency, clinical study, endothelial cells, endothelin-1, Hereditary angioedema, soluble E-selectin, von Willebrand factor",
author = "Erika Kajd{\'a}csi and Jani, {P{\'e}ter K.} and Dorottya Csuka and L. Varga and Z. Proh{\'a}szka and H. Farkas and L. Cerven{\'a}k",
year = "2014",
doi = "10.1016/j.jaci.2013.12.1072",
language = "English",
volume = "133",
pages = "1686--1691",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "6",

}

TY - JOUR

T1 - Endothelial cell activation during edematous attacks of hereditary angioedema types i and II

AU - Kajdácsi, Erika

AU - Jani, Péter K.

AU - Csuka, Dorottya

AU - Varga, L.

AU - Prohászka, Z.

AU - Farkas, H.

AU - Cervenák, L.

PY - 2014

Y1 - 2014

N2 - Background Hereditary angioedema (HAE) caused by C1-inhibitor (C1-INH) deficiency (HAE-C1-INH) is a potentially life-threatening rare disease caused by the decreased activity of C1-INH. Lack of C1-INH leads to overproduction of bradykinin, a potent vasoactive peptide. Although angioedema is induced by bradykinin, the function and activation of endothelial cells (ECs), the targets of bradykinin, have not yet been studied during HAE attacks. Objective We studied whether EC function is altered during HAE attacks in comparison with attack-free intervals. Methods Forty-six consecutive samples obtained during attacks from 18 patients with HAE-C1-INH were compared with inter-attack samples of the same patients. The patients' sera were tested for von Willebrand factor (VWF) antigen, VWF collagen-binding activity, soluble E-selectin, and endothelin-1 levels by using ELISA and BRAHMS Kryptor technologies. Results Levels of all 4 EC markers (VWF antigen, VWF collagen-binding activity, soluble E-selectin, and endothelin-1) were significantly increased during HAE attacks. Their increases were even more obvious in the subgroup of patients without any pre-existing risk factors for endothelial dysfunction. Conclusion In this study we demonstrated that ECs are activated during HAE attacks. Our results might suggest the need for revising the knowledge on the pathogenesis of HAE-C1-INH and for reconsidering the role of ECs as a possible novel therapeutic target in patients with this disease.

AB - Background Hereditary angioedema (HAE) caused by C1-inhibitor (C1-INH) deficiency (HAE-C1-INH) is a potentially life-threatening rare disease caused by the decreased activity of C1-INH. Lack of C1-INH leads to overproduction of bradykinin, a potent vasoactive peptide. Although angioedema is induced by bradykinin, the function and activation of endothelial cells (ECs), the targets of bradykinin, have not yet been studied during HAE attacks. Objective We studied whether EC function is altered during HAE attacks in comparison with attack-free intervals. Methods Forty-six consecutive samples obtained during attacks from 18 patients with HAE-C1-INH were compared with inter-attack samples of the same patients. The patients' sera were tested for von Willebrand factor (VWF) antigen, VWF collagen-binding activity, soluble E-selectin, and endothelin-1 levels by using ELISA and BRAHMS Kryptor technologies. Results Levels of all 4 EC markers (VWF antigen, VWF collagen-binding activity, soluble E-selectin, and endothelin-1) were significantly increased during HAE attacks. Their increases were even more obvious in the subgroup of patients without any pre-existing risk factors for endothelial dysfunction. Conclusion In this study we demonstrated that ECs are activated during HAE attacks. Our results might suggest the need for revising the knowledge on the pathogenesis of HAE-C1-INH and for reconsidering the role of ECs as a possible novel therapeutic target in patients with this disease.

KW - activation

KW - attack

KW - C1-inhibitor deficiency

KW - clinical study

KW - endothelial cells

KW - endothelin-1

KW - Hereditary angioedema

KW - soluble E-selectin

KW - von Willebrand factor

UR - http://www.scopus.com/inward/record.url?scp=84901765027&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901765027&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2013.12.1072

DO - 10.1016/j.jaci.2013.12.1072

M3 - Article

VL - 133

SP - 1686

EP - 1691

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 6

ER -