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Revista Española de Cardiología (English Edition) Revista Española de Cardiología (English Edition)
Rev Esp Cardiol. 2018;71:440-9 - Vol. 71 Num.06 DOI: 10.1016/j.rec.2017.06.019

Coronary Serum Obtained After Myocardial Infarction Induces Angiogenesis and Microvascular Obstruction Repair. Role of Hypoxia-inducible Factor-1A

César Ríos-Navarro a, Luisa Hueso a, Gema Miñana a,b,c, Julio Núñez a,b,c, Amparo Ruiz-Saurí a,d, María Jesús Sanz a,e, Joaquin Cànoves a,b,c,f, Francisco J. Chorro a,b,c,f, Laura Piqueras a,, Vicente Bodí a,b,c,f,

a Instituto de Investigación Sanitaria-INCLIVA, Valencia, Spain
b Servicio de Cardiología, Hospital Clínico Universitario, Valencia, Spain
c Departamento de Medicina, Universidad de Valencia, Valencia, Spain
d Departamento de Patología, Universidad de Valencia, Valencia, Spain
e Departamento de Farmacología, Universidad de Valencia, Valencia, Spain
f Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain

Refers to

Keywords

Myocardial infarction. Microvascular obstruction. Angiogenesis. Serum. Hypoxia-inducible factor-1A.

Abstract

Introduction and objectives

Microvascular obstruction (MVO) exerts deleterious effects following acute myocardial infarction (AMI). We investigated coronary angiogenesis induced by coronary serum and the role of hypoxia-inducible factor-1A (HIF-1A) in MVO repair.

Methods

Myocardial infarction was induced in swine by transitory 90-minute coronary occlusion. The pigs were divided into a control group and 4 AMI groups: no reperfusion, 1 minute, 1 week and 1 month after reperfusion. Microvascular obstruction and microvessel density were quantified. The proangiogenic effect of coronary serum drawn from coronary sinus on endothelial cells was evaluated using an in vitro tubulogenesis assay. Circulating and myocardial HIF-1A levels and the effect of in vitro blockade of HIF-1A was assessed.

Results

Compared with control myocardium, microvessel density decreased at 90-minute ischemia, and MVO first occurred at 1 minute after reperfusion. Both peaked at 1 week and almost completely resolved at 1 month. Coronary serum exerted a neoangiogenic effect on coronary endothelial cells in vitro, peaking at ischemia and 1 minute postreperfusion (32 ± 4 and 41 ± 9 tubes vs control: 3 ± 3 tubes; P < .01). Hypoxia-inducible factor-1A increased in serum during ischemia (5-minute ischemia: 273 ± 52 pg/mL vs control: 148 ± 48 pg/mL; P < .01) being present on microvessels of all AMI groups (no reperfusion: 67% ± 5% vs control: 15% ± 17%; P < .01). In vitro blockade of HIF-1A reduced the angiogenic response induced by serum.

Conclusions

Coronary serum represents a potent neoangiogenic stimulus even before reperfusion; HIF-1A might be crucial. Coronary neoangiogenesis induced by coronary serum can contribute to understanding the pathophysiology of AMI.

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1885-5857/© 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved