Heart Mitochondrial Proteome Study Elucidates Changes in Cardiac Energy Metabolism and Antioxidant PRDX3 in Human Dilated Cardiomyopathy

Fecha de publicación: 14/11/2014

Autores de IIS La Fe

• 

  Esther Roselló Lletí

  Autor

• Estefanía Tarazón Melguizo

  Autor

• Ana Ortega Gutierrez

  Autor

• María Micaela Molina Navarro

  Autor

• Carlos Gonzalez Juanatey

  Autor

• Antonio Salvador Sanz

  Autor

• Manuel Portoles Sanz

  Autor

• Jose Miguel Rivera Otero

  Autor

Participantes ajenos a IIS La Fe

• Barderas MG
• Otero M
• Lago F

Grupos

• Grupo de Investigación Clínica y Traslacional en Cardiología

  

  Investigador Principal

  Esther Roselló Lletí

Abstract

Background: Dilated cardiomyopathy (DCM) is a public health problem with no available curative treatment, and mitochondrial dysfunction plays a critical role in its development. The present study is the first to analyze the mitochondrial proteome in cardiac tissue of patients with DCM to identify potential molecular targets for its therapeutic intervention. Methods and Results: 16 left ventricular (LV) samples obtained from explanted human hearts with DCM (n = 8) and control donors (n = 8) were extracted to perform a proteomic approach to investigate the variations in mitochondrial protein expression. The proteome of the samples was analyzed by quantitative differential electrophoresis and Mass Spectrometry. These changes were validated by classical techniques and by novel and precise selected reaction monitoring analysis and RNA sequencing approach increasing the total heart samples up to 25. We found significant alterations in energy metabolism, especially in molecules involved in substrate utilization (ODPA, ETFD, DLDH), energy production (ATPA), other metabolic pathways (AL4A1) and protein synthesis (EFTU), obtaining considerable and specific relationships between the alterations detected in these processes. Importantly, we observed that the antioxidant PRDX3 overexpression is associated with impaired ventricular function. PRDX3 is significantly related to LV end systolic and diastolic diameter (r = 0.73, p value<0.01; r = 0.71, p value<0.01), fractional shortening, and ejection fraction (r = -0.61, p value < 0.05; and r = -20.62, p value< 0.05, respectively). Conclusion: This work could be a pivotal study to gain more knowledge on the cellular mechanisms related to the pathophysiology of this disease and may lead to the development of etiology-specific heart failure therapies. We suggest new molecular targets for therapeutic interventions, something that up to now has been lacking.