Abstract

This study investigates the activity and expression of lactate dehydrogenase (LDH) in idiopathic pulmonary arterial hypertension (IPAH) patients. IPAH is a rare and highly fatal disease with a median life expectancy at diagnosis of only 2.8 years. Ideally a simple blood test for biomarkers could simplify the physician’s diagnostic work-up, resulting in earlier diagnosis and successful institution of therapy. Recent publications suggest IPAH may behave like cancer, with monoclonal proliferation and a shared pathway of mitochondrial dysfunction. LDH is often upregulated in cancers, and a similar elevation is suspected in IPAH. Discovering similar patterns of flux in the cellular bioenergetics of IPAH and cancer would support the emerging theory that IPAH has a ‘cancer phenotype’. Quantitative proteomic analysis of fourteen lung tissue homogenate samples (seven lobectomy, seven IPAH) was performed using liquid chromatography – tandem mass spectrometry (LC-MS/MS). The lung samples, as well as 30 plasma samples (ten normal, 20 IPAH) were analysed for LDH fractional isoenzyme activity and expression. A pyruvate-to-lactate spectrophotometric activity assay was performed on the 44 samples, followed by LDH isoenzyme separation on thin-layer agarose gel and densitometric analysis. A significant link exists between IPAH and increased plasma and lung levels of LDH-1 (P = 0.0114 and 0.0262 respectively on Mann-Whitney U test). Receiver Operating Characteristic analysis demonstrated plasma LDH-1 had biomarker sensitivity and specificity of 80%. Measuring plasma LDH-1 appears clinically useful in diagnosing IPAH. This work supports the re-evaluation of IPAH as a cancer-like disease and suggests a new biomarker.