Circulating Sphingosine-1-Phosphate as A Non-Invasive Biomarker of Heart Transplant Rejection.

Autores de IIS La Fe

• Estefanía Tarazón Melguizo

  Autor

• Carolina Gil Cayuela

  Autor

• Marta Isabel Roca Marugán

  Autor

• José Francisco Dolz Lago

  Autor

• Carlos Gonzalez Juanatey

  Autor

• María Elena Sánchez Lacuesta

  Autor

• 

  Luis Vicente Martínez Dolz

  Autor

• Manuel Portoles Sanz

  Autor

• 

  Esther Roselló Lletí

  Autor

Participantes ajenos a IIS La Fe

• Manzanares MG

Grupos

• Cirugía digestiva y Cuidados perioperatorios

• Grupo de Investigación Clínica y Traslacional en Cardiología

• Regeneración y Trasplante Cardíaco

Abstract

Accumulating evidence has confirmed that the expression of sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is downregulated in heart failure and cardiac allograft rejection. Although many SERCA2a-related genes and proteins involved in the regulation of myocardial Ca 2+ fluxes have been explored, its related metabolites remain poorly studied. Our main objective was to identify circulating SERCA2a-related metabolites altered in cardiac allograft rejection and to determine whether these could serve as non-invasive biomarkers. Sixty plasma samples from adult heart transplant were included in a metabolomic analysis. Sphingosine-1 phosphate (S1P), metabolite closely related with SERCA, were increased in patients with cardiac rejection (p 0.0001). S1P discriminated between patients with and without rejection: normal grafts vs. all rejecting grafts (AUC = 0.911, p 0.0001), normal grafts vs. Grade 1 R (AUC = 0.819, p 0.01), Grade 2 R (AUC = 0.911, p 0.0001), Grade 3 R (AUC = 0.996, p 0.0001). In addition, we found changes in key enzymes and receptors of S1P pathway analysed on explanted hearts from heart failure patients. This preliminary study reveals that circulating S1P determination could be a novel approach to detect cardiac rejection, showing a robust capability for detection that improves gradually with the severity of rejection. These alterations could be relevant to better understand the involvement of calcium regulation on the pathophysiology of rejection.