César Ríos-Navarro1, Luisa Hueso1, Gema Miñana2, Julio Núñez2, Amparo Ruiz-Saurí3, María Jesús Sanz4, Joaquin Cànoves5, Francisco J Chorro5, Laura Piqueras6, Vicente Bodí7. 1. Instituto de Investigación Sanitaria-INCLIVA, Valencia, Spain. 2. Instituto de Investigación Sanitaria-INCLIVA, Valencia, Spain; Servicio de Cardiología, Hospital Clínico Universitario, Valencia, Spain; Departamento de Medicina, Universidad de Valencia, Valencia, Spain. 3. Instituto de Investigación Sanitaria-INCLIVA, Valencia, Spain; Departamento de Patología, Universidad de Valencia, Valencia, Spain. 4. Instituto de Investigación Sanitaria-INCLIVA, Valencia, Spain; Departamento de Farmacología, Universidad de Valencia, Valencia, Spain. 5. Instituto de Investigación Sanitaria-INCLIVA, Valencia, Spain; Servicio de Cardiología, Hospital Clínico Universitario, Valencia, Spain; Departamento de Medicina, Universidad de Valencia, Valencia, Spain; Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. 6. Instituto de Investigación Sanitaria-INCLIVA, Valencia, Spain. Electronic address: piqueras_lau@gva.es. 7. Instituto de Investigación Sanitaria-INCLIVA, Valencia, Spain; Servicio de Cardiología, Hospital Clínico Universitario, Valencia, Spain; Departamento de Medicina, Universidad de Valencia, Valencia, Spain; Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. Electronic address: vicente.bodi@uv.es.
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, 1minute, 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 1minute 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 1minute 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.
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, 1minute, 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 1minute 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 1minute 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.
Authors: Cesar Rios-Navarro; Maria Ortega; Victor Marcos-Garces; Jose Gavara; Elena de Dios; Nerea Perez-Sole; Francisco J Chorro; Vicente Bodi; Amparo Ruiz-Sauri Journal: BMC Vet Res Date: 2020-07-29 Impact factor: 2.741
Authors: Cesar Rios-Navarro; Jose Gavara; Veronica Vidal; Clara Bonanad; Paolo Racugno; Antoni Bayes-Genis; Gema Miñana; Oliver Husser; Ricardo Oltra; Julio Nuñez; Francisco J Chorro; Vicente Bodi; Amparo Ruiz-Sauri Journal: PLoS One Date: 2018-10-26 Impact factor: 3.240