title: mRNA PGC-1α levels in blood samples reliably correlates with its myocardial expression: study in patients undergoing cardiac surgery.
abstract: OBJECTIVE
  Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a transcriptional coactivator that has been proposed to play a protective role in mouse models of cardiac ischemia and heart failure, suggesting that PGC-1α could be relevant as a prognostic marker. Our previous studies showed that the estimation of peripheral mRNA PGC-1α expression was feasible and that its induction correlated with the extent of myocardial necrosis and left ventricular remodeling in patients with myocardial infarction. In this study, we sought to determine if the myocardial and peripheral expressions of PGC-1α are well correlated and to analyze the variability of PGC-1α expression depending on the prevalence of some metabolic disorders.
  
  
  METHODS
  This was a cohort of 35 consecutive stable heart failure patients with severe aortic stenosis who underwent an elective aortic valve replacement surgery. mRNA PGC-1α expression was simultaneously determined from myocardial biopsy specimens and blood samples obtained during surgery by quantitative PCR, and a correlation between samples was made using the Kappa index. Patients were divided into two groups according to the detection of baseline expression levels of PGC-1α in blood samples, and comparisons between both groups were made by chi-square test or unpaired Student's t-test as appropriate.
  
  
  RESULTS
  Based on myocardial biopsies, we found that mRNA PGC-1α expression in blood samples showed a statistically significant correlation with myocardial expression (Kappa index 0.66, p<0.001). The presence of higher systemic PGC-1α expression was associated with a greater expression of some target genes such as silent information regulator 2 homolog-1 (x-fold expression in blood samples: 4.43±5.22 vs. 1.09±0.14, p=0.044) and better antioxidant status in these patients (concentration of Trolox: 0.40±0.05 vs. 0.34±0.65, p=0.006).
  
  
  CONCLUSIONS
  Most patients with higher peripheral expression also had increased myocardial expression, so we conclude that the non-invasive estimation of mRNA PGC-1α expression from blood samples provides a good approach of the constitutive status of the mitochondrial protection system regulated by PGC-1α and that this could be used as prognostic indicator in cardiovascular disease.
authors.affiliation: Cardiovascular Institute, General University Hospital, Valencia-Spain. osfabregat@gmail.com.
authors.forename: Oscar
authors.initials: O
authors.lastname: Fabregat-Andres
authors.affiliation: Cardiovascular Institute, General University Hospital, Valencia-Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Paredes
authors.affiliation: Cardiovascular Institute, General University Hospital, Valencia-Spain.
authors.forename: María
authors.initials: M
authors.lastname: Monsalve
authors.affiliation: Cardiovascular Institute, General University Hospital, Valencia-Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Milara
authors.affiliation: Cardiovascular Institute, General University Hospital, Valencia-Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Ridocci-Soriano
authors.affiliation: Cardiovascular Institute, General University Hospital, Valencia-Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Gonzalez-Hervas
authors.affiliation: Cardiovascular Institute, General University Hospital, Valencia-Spain.
authors.forename: Armando
authors.initials: A
authors.lastname: Mena
authors.affiliation: Cardiovascular Institute, General University Hospital, Valencia-Spain.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Facila
authors.affiliation: Cardiovascular Institute, General University Hospital, Valencia-Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Hornero
authors.affiliation: Cardiovascular Institute, General University Hospital, Valencia-Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Morell
authors.affiliation: Cardiovascular Institute, General University Hospital, Valencia-Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Martinez-Leon
authors.affiliation: Research Foundation, General University Hospital, Valencia-Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Cortijo