Thromb Haemost 2014; 112(01): 87-95
DOI: 10.1160/TH13-08-0721
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

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

Roxana Martinez-Pinna*
1   Vascular Research Lab and Vascular Surgery, IIS-Fundación Jiménez Díaz-Autonoma University, Madrid, Spain
,
Jes S. Lindholt*
2   Departments of Heart, Thoracic and Vascular Surgery, University Hospitals of Odense and Aarhus, Denmark
,
Julio Madrigal-Matute
1   Vascular Research Lab and Vascular Surgery, IIS-Fundación Jiménez Díaz-Autonoma University, Madrid, Spain
,
Luis M. Blanco-Colio
1   Vascular Research Lab and Vascular Surgery, IIS-Fundación Jiménez Díaz-Autonoma University, Madrid, Spain
,
Margarita Esteban-Salan
3   Hospital de Cruces, Bilbao, Spain
,
Monica Maria Torres-Fonseca
1   Vascular Research Lab and Vascular Surgery, IIS-Fundación Jiménez Díaz-Autonoma University, Madrid, Spain
,
Thibault Lefebvre
4   INSERM U773, Univ Paris Diderot, Sorbonne Paris Cité, AP-HP, Hôpital Louis Mourier, Colombes, France
,
Sandrine Delbosc
5   U698 and UMR 1148, Univ Paris Diderot, Sorbonne Paris Cité, AP-HP, Hôpital Bichat, Paris, France
,
Jesper Laustsen
2   Departments of Heart, Thoracic and Vascular Surgery, University Hospitals of Odense and Aarhus, Denmark
,
Fathi Driss
6   Inserm, U773, Univ Paris Diderot, Sorbonne Paris Cité, AP-HP, Biochemistry Department, Hôpital Bichat, Paris, France
,
Melina Vega de Ceniga
7   Vascular Surgery, Hospital Galdakao, Bilbao, Spain
,
Laurent Gouya
8   INSERM U773, Univ Versailles Saint Quentin-en-Yvelines, AP-HP, Hôpital Ambroise Paré, France
,
Günter Weiss
9   Department of Internal Medicine VI, Medical University of Innsbruck, Austria
,
Jesus Egido
1   Vascular Research Lab and Vascular Surgery, IIS-Fundación Jiménez Díaz-Autonoma University, Madrid, Spain
10   Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain
,
Olivier Meilhac
5   U698 and UMR 1148, Univ Paris Diderot, Sorbonne Paris Cité, AP-HP, Hôpital Bichat, Paris, France
,
Jean-Baptiste Michel
5   U698 and UMR 1148, Univ Paris Diderot, Sorbonne Paris Cité, AP-HP, Hôpital Bichat, Paris, France
,
Jose L. Martin-Ventura
1   Vascular Research Lab and Vascular Surgery, IIS-Fundación Jiménez Díaz-Autonoma University, Madrid, Spain
› Author Affiliations
Financial support: This work was supported by the EC, FAD project (FP-7, HEALTH F2–2008–200647), the Spanish MICIN (SAF2010/21852), Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, Redes RIC (RD12/0042/00038) and biobancos (RD09/0076/00101), PI10/00072, Fundación Lilly and FRIAT.
Further Information

Publication History

Received: 02 September 2013

Accepted after major revision: 06 February 2014

Publication Date:
01 December 2017 (online)

Summary

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.

* Equal contribution of these authors.


 
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