Department of Molecular Medicine, Research Foundation of the University General Hospital of Valencia, 46014 Valencia, Spain.
Oxid Med Cell Longev. 2012;2012:236572. doi: 10.1155/2012/236572. Epub 2012 Aug 29.
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.
特发性肺动脉高压(IPAH)的特征是肺血管的阻塞性重塑,以及肺动脉压(PAP)的进行性升高,随后出现右心衰竭和死亡。缺氧诱导过氧化物酶体增殖物激活受体γ共激活因子-1α(PGC-1α)的表达,后者调节氧化代谢和线粒体生物发生。我们分析了 IPAH 患者血液样本中 PGC-1α、细胞色素 C(CYTC)、超氧化物歧化酶(SOD)、总抗氧化状态(TAS)和谷胱甘肽过氧化物酶(GPX)的活性。在 IPAH 患者中检测到 PGC-1α的表达,但在健康志愿者中未检测到。与对照组相比,IPAH 患者的 SOD mRNA 水平较低(3.93±0.89 倍变化)。与健康供体相比,患者的 TAS 和 GPX 活性也较低,分别为(0.13±0.027 与 0.484±0.048 mM 和 56.034±10.37 与 165.46±11.38 nmol/min/mL)。我们发现 PGC-1α 的表达水平与年龄、PAP 和 PVR 呈负相关,与 CI、PaO2、CYTC 和 SOD mRNA 水平、TAS 和 GPX 活性呈正相关。这些结果表明 PGC-1α 可能作为 IPAH 进展的潜在生物标志物。