title: PGC-1α induction in pulmonary arterial hypertension.
abstract: Idiopathic Pulmonary arterial hypertension (IPAH) is characterized by the obstructive remodelling of pulmonary arteries, and a progressive elevation in pulmonary arterial pressure (PAP) with subsequent right-sided heart failure and dead. Hypoxia induces the expression of peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α) which regulates oxidative metabolism and mitochondrial biogenesis. We have analysed the expression of PGC-1α, cytochrome C (CYTC), superoxide dismutase (SOD), the total antioxidant status (TAS) and the activity of glutathione peroxidase (GPX) in blood samples of IPAH patients. Expression of PGC-1α was detected in IPAH patients but not in healthy volunteers. The mRNA levels of SOD were lower in IPAH patients compared to controls (3.93 ± 0.89 fold change). TAS and GPX activity were lower too in patients compared to healthy donors, (0.13 ± 0.027 versus 0.484 ± 0.048 mM and 56.034 ± 10.37 versus 165.46 ± 11.38 nmol/min/mL, resp.). We found a negative correlation between expression levels of PGC-1α and age, PAP and PVR, as well as a positive correlation with CI, PaO(2), mRNA levels of CYTC and SOD, TAS and GPX activity. These results taken together are indicative of the possible role of PGC-1α as a potential biomarker of the progression of IPAH.
authors.affiliation: Department of Molecular Medicine, Research Foundation of the University General Hospital of Valencia, 46014 Valencia, Spain. mata_manroi@gva.es
authors.forename: Manuel
authors.initials: M
authors.lastname: Mata
authors.forename: Irene
authors.initials: I
authors.lastname: Sarrion
authors.forename: Lara
authors.initials: L
authors.lastname: Milian
authors.forename: Gustavo
authors.initials: G
authors.lastname: Juan
authors.forename: Mercedes
authors.initials: M
authors.lastname: Ramon
authors.forename: Dolores
authors.initials: D
authors.lastname: Naufal
authors.forename: Juan
authors.initials: J
authors.lastname: Gil
authors.forename: F
authors.initials: F
authors.lastname: Ridocci
authors.forename: O
authors.initials: O
authors.lastname: Fabregat-Andrés
authors.forename: Julio
authors.initials: J
authors.lastname: Cortijo
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D002712:Chlorides / Q000737:chemistry; D045304:Cytochromes c / Q000097:blood / Q000235:genetics; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood / Q000235:genetics; D006360:Heat-Shock Proteins / Q000097:blood* / Q000235:genetics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D013482:Superoxide Dismutase / Q000097:blood / Q000235:genetics; D014157:Transcription Factors / Q000097:blood* / Q000235:genetics; D014655:Vascular Resistance
chemical_list: D002712:Chlorides; D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D045304:Cytochromes c; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase