Selective increase of cardiomyocyte derived extracellular vesicles after experimental myocardial infarction and functional effects on the endothelium.

INTRODUCTION: Wound healing after myocardial infarction (MI) is mediated by different cell types, secreted proteins, components of the extracellular matrix (ECM) and, as increasing evidences suggest, extracellular vesicles (EVs). We aim to determine the dynamics of release and origin of EVs after MI, as well as their biological activity on endothelial cells (ECs). METHODS: MI was induced in WT mice and blood and tissues collected at baseline, 3, 15 and 30 days post-ligation for cardiac function (echocardiography) and histological evaluation. Circulating EVs subpopulations were measured by flow cytometry in mouse, and in a small cohort of patients with ST-segment elevation MI (STEMI, n = 6). In vitro, EVs were isolated from a cardiomyocyte cell line (HL1) and their function assayed on ECs. RESULTS: Leukocyte and endothelial EVs increased concomitant to inflammatory and angiogenic processes triggered by ischemia. More strikingly, cardiomyocyte EVs (connexin43+) were detected in STEMI patients and in murine MI, where a significant increase in their levels was reported at day 15 post-ischemia (p < 0.05 vs baseline). In vitro, HL1EVs induced ECs migration (p = 0.05) and proliferation (p < 0.05), but impaired tube formation. These apparent contradictory results could be partially explained by the upregulation of MMP3, and the apoptosis and senescence genes, p53 and p16, induced by HL1EVs on ECs (p < 0.05). CONCLUSIONS: MI induces the release of different EVs subpopulations, including those of cardiac origin, in a preclinical model of MI and STEMI patients. In vitro, cardiomyocyte derived EVs are able to modulate endothelial function, suggesting their active role in heart repair after ischemia.

Fibrilación auricular y cardiopatía isquémica: más allá de la prevención del ictus / Atrial fibrillation and ischemic heart disease: beyond stroke prevention

El objetivo principal en el abordaje del paciente con fibrilación auricular es la reducción del riesgo de ictus mediante el tratamiento antitrombótico adecuado. Sin embargo, a pesar de una adecuada anticoagulación, sigue habiendo un importante riesgo residual de eventos isquémicos, particularmente infarto de miocardio y muerte de origen cardiovascular, que exige una protección más completa. Por lo tanto, en el paciente con fibrilación auricular, el tratamiento anticoagulante debería perseguir este doble objetivo, la reducción tanto del riesgo de ictus como de las complicaciones isquémicas. Diferentes estudios han demostrado que los antagonistas de la vitamina K solo disminuyen el riesgo de ictus y de eventos isquémicos cuando el control de la anticoagulación es óptimo, cosa que ocurre en un pequeño número de pacientes. Con respecto a los anticoagulantes orales de acción directa, aunque en general muestran un perfil de eficacia y seguridad mejor que los antagonistas de la vitamina K, parece que no todos ofrecerían la misma protección en cuanto a la reducción de los eventos isquémicos. Está demostrado que el rivaroxabán reduce de manera significativa (18%) el riesgo de infarto de miocardio. De hecho, los estudios muestran que el rivaroxabán proporciona una protección vascular más completa en diferentes contextos clínicos, no solo en el paciente con fibrilación auricular, sino también en el paciente con enfermedad vascular ateroesclerótica

The main aim of management in patients with atrial fibrillation is to reduce the risk of stroke using appropriate antithrombotic treatment. However, despite adequate anticoagulation, there remains a substantial residual risk of ischemic events, particularly myocardial infarction and cardiovascular death. A more general approach is needed. Consequently, in patients with atrial fibrillation, anticoagulation treatment should seek to achieve the twin targets of reducing the risk of both stroke and ischemic events. Studies have demonstrated that vitamin K antagonists reduce the risk of stroke and ischemic events only when anticoagulation control is optimal, a situation that occurs in only a small number of patients. Direct oral anticoagulants are generally more effective and safer than vitamin K antagonists. However, not all direct oral anticoagulants appear to offer the same protection against ischemic events. It has been shown that rivaroxaban significantly reduces the risk of myocardial infarction (by 18%). In fact, studies demonstrate that rivaroxaban provides comprehensive vascular protection across a range of clinical scenarios, not only in patients with atrial fibrillation, but also in those with atherosclerotic vascular disease