From tissue iron retention to low systemic haemoglobin levels, new pathophysiological biomarkers of human abdominal aortic aneurysm

Roxana Martinez-Pinna, Jes S. Lindholt, Julio Madrigal-Matute, Luis M. Blanco-Colio, Margarita Esteban-Salan, Monica Maria Torres-Fonseca, Thibault Lefebvre, Sandrine Delbosc, Jesper Laustsen, Fathi Driss, Melina Vega de Ceniga, Laurent Gouya, Günter Weiss, Jesus Egido, Olivier Meilhac, Jean Baptiste Michel, Jose L. Martin-Ventura

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Iron deposits are observed in tissue of abdominal aortic aneurysm (AAA) patients, although the underlying mechanisms are not completely elucidated. Therefore we explored circulating markers of iron metabolism in AAA patients, and tested if they could serve as biomarkers of AAA. Increased red blood cell (RBC)-borne iron retention and transferrin, transferrin receptor and ferritin expression was observed in AAA tissue compared to control aorta (immunohistochemistry and western blot). In contrast, decreased circulating iron, transferrin, mean corpuscular haemoglobin concentration (MCHC) and haemoglobin concentration, along with circulating RBC count, were observed in AAA patients (aortic diameter >3 cm, n=114) compared to controls (aortic diameter <3 cm, n=88) (ELISA), whereas hepcidin concentrations were increased in AAA subjects (MS/MS assay). Moreover, iron, transferrin and haemoglobin levels were negatively, and hepcidin positively, correlated with aortic diameter in AAA patients. The association of low haemoglobin with AAA presence or aortic diameter was independent of specific risk factors. Moreover, MCHC negatively correlated with thrombus area in another cohort of AAA patients (aortic diameter 3-5 cm, n=357). We found that anaemia was significantly more prevalent in AAA patients (aortic diameter >5 cm, n=8,912) compared to those in patients with atherosclerotic aorto-iliac occlusive disease (n=17,737) [adjusted odds ratio=1.77 (95% confidence interval: 1.61;1.93)]. Finally, the mortality risk among AAA patients with anaemia was increased by almost 30% [adjusted hazard ratio: 1.29 (95% confidence interval: 1.16;1.44)] as compared to AAA subjects without anaemia. In conclusion, local iron retention and altered iron recycling associated to high hepcidin and low transferrin systemic concentrations could lead to reduced circulating haemoglobin levels in AAA patients. Low haemoglobin levels are independently associated to AAA presence and clinical outcome.

Original languageEnglish (US)
Pages (from-to)87-95
Number of pages9
JournalThrombosis and Haemostasis
Volume112
Issue number1
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Abdominal Aortic Aneurysm
Hemoglobins
Iron
Biomarkers
Transferrin
Anemia
Confidence Intervals
Hepcidins
Erythrocyte Count
Transferrin Receptors
Erythrocyte Indices
Recycling
Ferritins
Aorta
Erythrocytes
Western Blotting
Immunohistochemistry
Odds Ratio
Mortality

Keywords

  • Anaemia
  • Haemoglobin
  • Hepcidin
  • Iron
  • RBC
  • Transferrin

ASJC Scopus subject areas

  • Hematology

Cite this

Martinez-Pinna, R., Lindholt, J. S., Madrigal-Matute, J., Blanco-Colio, L. M., Esteban-Salan, M., Torres-Fonseca, M. M., ... Martin-Ventura, J. L. (2014). From tissue iron retention to low systemic haemoglobin levels, new pathophysiological biomarkers of human abdominal aortic aneurysm. Thrombosis and Haemostasis, 112(1), 87-95. https://doi.org/10.1160/TH13-08-0721

From tissue iron retention to low systemic haemoglobin levels, new pathophysiological biomarkers of human abdominal aortic aneurysm. / Martinez-Pinna, Roxana; Lindholt, Jes S.; Madrigal-Matute, Julio; Blanco-Colio, Luis M.; Esteban-Salan, Margarita; Torres-Fonseca, Monica Maria; Lefebvre, Thibault; Delbosc, Sandrine; Laustsen, Jesper; Driss, Fathi; de Ceniga, Melina Vega; Gouya, Laurent; Weiss, Günter; Egido, Jesus; Meilhac, Olivier; Michel, Jean Baptiste; Martin-Ventura, Jose L.

In: Thrombosis and Haemostasis, Vol. 112, No. 1, 2014, p. 87-95.

Research output: Contribution to journalArticle

Martinez-Pinna, R, Lindholt, JS, Madrigal-Matute, J, Blanco-Colio, LM, Esteban-Salan, M, Torres-Fonseca, MM, Lefebvre, T, Delbosc, S, Laustsen, J, Driss, F, de Ceniga, MV, Gouya, L, Weiss, G, Egido, J, Meilhac, O, Michel, JB & Martin-Ventura, JL 2014, 'From tissue iron retention to low systemic haemoglobin levels, new pathophysiological biomarkers of human abdominal aortic aneurysm', Thrombosis and Haemostasis, vol. 112, no. 1, pp. 87-95. https://doi.org/10.1160/TH13-08-0721
Martinez-Pinna, Roxana ; Lindholt, Jes S. ; Madrigal-Matute, Julio ; Blanco-Colio, Luis M. ; Esteban-Salan, Margarita ; Torres-Fonseca, Monica Maria ; Lefebvre, Thibault ; Delbosc, Sandrine ; Laustsen, Jesper ; Driss, Fathi ; de Ceniga, Melina Vega ; Gouya, Laurent ; Weiss, Günter ; Egido, Jesus ; Meilhac, Olivier ; Michel, Jean Baptiste ; Martin-Ventura, Jose L. / From tissue iron retention to low systemic haemoglobin levels, new pathophysiological biomarkers of human abdominal aortic aneurysm. In: Thrombosis and Haemostasis. 2014 ; Vol. 112, No. 1. pp. 87-95.
@article{cbe61735f54543ad9ffc0728263a695e,
title = "From tissue iron retention to low systemic haemoglobin levels, new pathophysiological biomarkers of human abdominal aortic aneurysm",
abstract = "Iron deposits are observed in tissue of abdominal aortic aneurysm (AAA) patients, although the underlying mechanisms are not completely elucidated. Therefore we explored circulating markers of iron metabolism in AAA patients, and tested if they could serve as biomarkers of AAA. Increased red blood cell (RBC)-borne iron retention and transferrin, transferrin receptor and ferritin expression was observed in AAA tissue compared to control aorta (immunohistochemistry and western blot). In contrast, decreased circulating iron, transferrin, mean corpuscular haemoglobin concentration (MCHC) and haemoglobin concentration, along with circulating RBC count, were observed in AAA patients (aortic diameter >3 cm, n=114) compared to controls (aortic diameter <3 cm, n=88) (ELISA), whereas hepcidin concentrations were increased in AAA subjects (MS/MS assay). Moreover, iron, transferrin and haemoglobin levels were negatively, and hepcidin positively, correlated with aortic diameter in AAA patients. The association of low haemoglobin with AAA presence or aortic diameter was independent of specific risk factors. Moreover, MCHC negatively correlated with thrombus area in another cohort of AAA patients (aortic diameter 3-5 cm, n=357). We found that anaemia was significantly more prevalent in AAA patients (aortic diameter >5 cm, n=8,912) compared to those in patients with atherosclerotic aorto-iliac occlusive disease (n=17,737) [adjusted odds ratio=1.77 (95{\%} confidence interval: 1.61;1.93)]. Finally, the mortality risk among AAA patients with anaemia was increased by almost 30{\%} [adjusted hazard ratio: 1.29 (95{\%} confidence interval: 1.16;1.44)] as compared to AAA subjects without anaemia. In conclusion, local iron retention and altered iron recycling associated to high hepcidin and low transferrin systemic concentrations could lead to reduced circulating haemoglobin levels in AAA patients. Low haemoglobin levels are independently associated to AAA presence and clinical outcome.",
keywords = "Anaemia, Haemoglobin, Hepcidin, Iron, RBC, Transferrin",
author = "Roxana Martinez-Pinna and Lindholt, {Jes S.} and Julio Madrigal-Matute and Blanco-Colio, {Luis M.} and Margarita Esteban-Salan and Torres-Fonseca, {Monica Maria} and Thibault Lefebvre and Sandrine Delbosc and Jesper Laustsen and Fathi Driss and {de Ceniga}, {Melina Vega} and Laurent Gouya and G{\"u}nter Weiss and Jesus Egido and Olivier Meilhac and Michel, {Jean Baptiste} and Martin-Ventura, {Jose L.}",
year = "2014",
doi = "10.1160/TH13-08-0721",
language = "English (US)",
volume = "112",
pages = "87--95",
journal = "Thrombosis and Haemostasis",
issn = "0340-6245",
publisher = "Schattauer GmbH",
number = "1",

}

TY - JOUR

T1 - From tissue iron retention to low systemic haemoglobin levels, new pathophysiological biomarkers of human abdominal aortic aneurysm

AU - Martinez-Pinna, Roxana

AU - Lindholt, Jes S.

AU - Madrigal-Matute, Julio

AU - Blanco-Colio, Luis M.

AU - Esteban-Salan, Margarita

AU - Torres-Fonseca, Monica Maria

AU - Lefebvre, Thibault

AU - Delbosc, Sandrine

AU - Laustsen, Jesper

AU - Driss, Fathi

AU - de Ceniga, Melina Vega

AU - Gouya, Laurent

AU - Weiss, Günter

AU - Egido, Jesus

AU - Meilhac, Olivier

AU - Michel, Jean Baptiste

AU - Martin-Ventura, Jose L.

PY - 2014

Y1 - 2014

N2 - Iron deposits are observed in tissue of abdominal aortic aneurysm (AAA) patients, although the underlying mechanisms are not completely elucidated. Therefore we explored circulating markers of iron metabolism in AAA patients, and tested if they could serve as biomarkers of AAA. Increased red blood cell (RBC)-borne iron retention and transferrin, transferrin receptor and ferritin expression was observed in AAA tissue compared to control aorta (immunohistochemistry and western blot). In contrast, decreased circulating iron, transferrin, mean corpuscular haemoglobin concentration (MCHC) and haemoglobin concentration, along with circulating RBC count, were observed in AAA patients (aortic diameter >3 cm, n=114) compared to controls (aortic diameter <3 cm, n=88) (ELISA), whereas hepcidin concentrations were increased in AAA subjects (MS/MS assay). Moreover, iron, transferrin and haemoglobin levels were negatively, and hepcidin positively, correlated with aortic diameter in AAA patients. The association of low haemoglobin with AAA presence or aortic diameter was independent of specific risk factors. Moreover, MCHC negatively correlated with thrombus area in another cohort of AAA patients (aortic diameter 3-5 cm, n=357). We found that anaemia was significantly more prevalent in AAA patients (aortic diameter >5 cm, n=8,912) compared to those in patients with atherosclerotic aorto-iliac occlusive disease (n=17,737) [adjusted odds ratio=1.77 (95% confidence interval: 1.61;1.93)]. Finally, the mortality risk among AAA patients with anaemia was increased by almost 30% [adjusted hazard ratio: 1.29 (95% confidence interval: 1.16;1.44)] as compared to AAA subjects without anaemia. In conclusion, local iron retention and altered iron recycling associated to high hepcidin and low transferrin systemic concentrations could lead to reduced circulating haemoglobin levels in AAA patients. Low haemoglobin levels are independently associated to AAA presence and clinical outcome.

AB - Iron deposits are observed in tissue of abdominal aortic aneurysm (AAA) patients, although the underlying mechanisms are not completely elucidated. Therefore we explored circulating markers of iron metabolism in AAA patients, and tested if they could serve as biomarkers of AAA. Increased red blood cell (RBC)-borne iron retention and transferrin, transferrin receptor and ferritin expression was observed in AAA tissue compared to control aorta (immunohistochemistry and western blot). In contrast, decreased circulating iron, transferrin, mean corpuscular haemoglobin concentration (MCHC) and haemoglobin concentration, along with circulating RBC count, were observed in AAA patients (aortic diameter >3 cm, n=114) compared to controls (aortic diameter <3 cm, n=88) (ELISA), whereas hepcidin concentrations were increased in AAA subjects (MS/MS assay). Moreover, iron, transferrin and haemoglobin levels were negatively, and hepcidin positively, correlated with aortic diameter in AAA patients. The association of low haemoglobin with AAA presence or aortic diameter was independent of specific risk factors. Moreover, MCHC negatively correlated with thrombus area in another cohort of AAA patients (aortic diameter 3-5 cm, n=357). We found that anaemia was significantly more prevalent in AAA patients (aortic diameter >5 cm, n=8,912) compared to those in patients with atherosclerotic aorto-iliac occlusive disease (n=17,737) [adjusted odds ratio=1.77 (95% confidence interval: 1.61;1.93)]. Finally, the mortality risk among AAA patients with anaemia was increased by almost 30% [adjusted hazard ratio: 1.29 (95% confidence interval: 1.16;1.44)] as compared to AAA subjects without anaemia. In conclusion, local iron retention and altered iron recycling associated to high hepcidin and low transferrin systemic concentrations could lead to reduced circulating haemoglobin levels in AAA patients. Low haemoglobin levels are independently associated to AAA presence and clinical outcome.

KW - Anaemia

KW - Haemoglobin

KW - Hepcidin

KW - Iron

KW - RBC

KW - Transferrin

UR - http://www.scopus.com/inward/record.url?scp=84902132532&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902132532&partnerID=8YFLogxK

U2 - 10.1160/TH13-08-0721

DO - 10.1160/TH13-08-0721

M3 - Article

C2 - 24599423

AN - SCOPUS:84902132532

VL - 112

SP - 87

EP - 95

JO - Thrombosis and Haemostasis

JF - Thrombosis and Haemostasis

SN - 0340-6245

IS - 1

ER -