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

15 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Hematology

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    Martinez-Pinna, R., Lindholt, J. S., Madrigal-Matute, J., Blanco-Colio, L. M., Esteban-Salan, M., Torres-Fonseca, M. M., Lefebvre, T., Delbosc, S., Laustsen, J., Driss, F., de Ceniga, M. V., Gouya, L., Weiss, G., Egido, J., Meilhac, O., Michel, J. B., & 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