Implications of Iron Deficiency in STEMI Patients and in a Murine Model of Myocardial Infarction

Javier Inserte; José A Barrabés; David Aluja; Imanol Otaegui; Jordi Bañeras; Laura Castellote; Ana Sánchez; José F Rodríguez-Palomares; Víctor Pineda; Elisabet Miró-Casas; Laia Milà; Rosa-Maria Lidón; Antonia Sambola; Filipa Valente; Agnès Rafecas; Marisol Ruiz-Meana; Antonio Rodríguez-Sinovas; Begoña Benito; Irene Buera; Sara Delgado-Tomás; David Beneítez; Ignacio Ferreira-González

doi:10.1016/j.jacbts.2021.05.004

Implications of Iron Deficiency in STEMI Patients and in a Murine Model of Myocardial Infarction

JACC Basic Transl Sci. 2021 Jul 26;6(7):567-580. doi: 10.1016/j.jacbts.2021.05.004. eCollection 2021 Jul.

Authors

Javier Inserte^{1

2

3}, José A Barrabés^{1

2

3}, David Aluja^{1

2

3}, Imanol Otaegui^{1

2

3}, Jordi Bañeras^{1

2

3}, Laura Castellote⁴, Ana Sánchez^{1

2

3}, José F Rodríguez-Palomares^{1

2

3}, Víctor Pineda⁵, Elisabet Miró-Casas^{1

2

3}, Laia Milà^{1

2

3}, Rosa-Maria Lidón^{1

2

3}, Antonia Sambola^{1

2

3}, Filipa Valente^{1

2

3}, Agnès Rafecas^{1

2

3}, Marisol Ruiz-Meana^{1

2

3}, Antonio Rodríguez-Sinovas^{1

2

3}, Begoña Benito^{1

2

3}, Irene Buera^{1

2

3}, Sara Delgado-Tomás^{1

2

3}, David Beneítez⁶, Ignacio Ferreira-González^{1

2

3}

Affiliations

¹ Department of Cardiology, Vall d'Hebron Hospital Universitari and Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
² Universitat Autònoma de Barcelona, Bellaterra, Spain.
³ Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
⁴ Department of Biochemistry, Vall d'Hebron Hospital Universitari, Barcelona, Spain.
⁵ Institut de Diagnòstic per la Imatge, Barcelona, Spain.
⁶ Department of Hematology, Vall d'Hebron Hospital Universitari and Vall d'Hebron Institut d'Oncologia (VHIO), Barcelona, Spain.

Abstract

In patients with a first anterior ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention, iron deficiency (ID) was associated with larger infarcts, more extensive microvascular obstruction, and higher frequency of adverse left ventricular remodeling as assessed by cardiac magnetic resonance imaging. In mice, an ID diet reduced the activity of the endothelial nitric oxide synthase/soluble guanylate cyclase/protein kinase G pathway in association with oxidative/nitrosative stress and increased infarct size after transient coronary occlusion. Iron supplementation or administration of an sGC activator before ischemia prevented the effects of the ID diet in mice. Not only iron excess, but also ID, may have deleterious effects in the setting of ischemia and reperfusion.

Keywords: CK-MB, creatine kinase-myocardial band; CMR, cardiac magnetic resonance; HSP90, heat-shock protein 90; ID, iron deficiency; LV, left ventricular; MVO, microvascular obstruction; PKG, protein kinase G; STEMI, ST-segment elevation acute myocardial infarction; STIR, short tau inversion recovery; VASP, vasodilator-stimulated phosphoprotein; acute myocardial infarction; eNOS, endothelial nitric oxide synthase; endothelial nitric oxide synthase; iNOS, inducible nitric oxide synthase; iron deficiency; myocardial reperfusion; sGC, soluble guanylyl cyclase; soluble guanylate cyclase.