Thickness and an Altered miRNA Expression in the Epicardial Adipose Tissue Is Associated With Coronary Heart Disease in Sudden Death Victims.

Autores de IIS La Fe

• Josep Mari Alexandre

  Autor

• Moises Barcelo Molina

  Autor

• Jorge Sanz Sánchez

  Autor

• Pilar Molina Aguilar

  Autor

• Jenifer Sancho Jiménez

  Autor

• Yolanda Abellán Pinar

  Autor

• Juan Giner Blasco

  Autor

• 

  Luis Vicente Martínez Dolz

  Autor

• Amparo Estelles Cortes

  Autor

• 

  Aitana Braza Boils

  Autor

• 

  Esther Zorio Grima

  Autor

Participantes ajenos a IIS La Fe

• Santaolaria-Ayora ML

Grupos

• Cardiopatías familiares, muerte súbita y mecanismos de enfermedad (CAFAMUSME)

• Grupo de Investigación Clínica y Traslacional en Cardiología

Abstract

INTRODUCTION AND OBJECTIVES: An increased epicardial adipose tissue (EAT) thickness has become a new risk factor for coronary heart disease (CHD). We aimed to study the role of EAT dysfunction as a CHD marker by focusing on its thickness and microRNA (miRNA) expression profile, and the potential factors possibly influencing them. METHODS: One hundred and fifty-five CHD sudden cardiac death victims and 84 non-CHD-sudden death controls were prospectively enrolled at autopsy. A representative subset underwent EAT thickness measurements and EAT miRNA expression profiling. RESULTS: Epicardial adipose tissue thickness was increased and allowed an accurate diagnosis of patient status (among other measurements, EAT score area under the curve 0.718, P < .001). Epicardial adipose tissue from patients showed 14 up- and 14 down-regulated miRNAs and miR-34a-3p, -34a-5p, -124-3p, -125a-5p, 628-5p, -1303 and -4286 were validated by quantitative real-time polymerase chain reaction. Patients exhibited higher EAT levels of miR-34a-3p and -34a-5p than controls (with a positive trend considering EAT from coronaries without stenosis, with stable stenosis and complicated plaques) and correlated with age only in controls. The mild positive correlation between liver and EAT miR-34a-5p levels in patients (r = 0.295, P = .020) dramatically increased in EAT from complicated plaques (r = 0.799, P = .017). Similar correlations were observed for high-sensitivity-C-reactive protein levels and miR-34a-5p levels both in EAT and liver extracts. CONCLUSIONS: Increased age-independent levels of miR-34a-3p and -34a-5p characterize the EAT miRNA expression profile of CHD regardless of EAT thickness, anthropometric parameters, and the presence of underlying atherosclerotic plaques.

Keywords

• Coronary heart disease; Enfermedad coronaria; Epicardial fat; Grasa epicardica; MicroARN; MicroRNA; Muerte subita; Sudden death