Abstract 3469: OPG:TRAIL Ratio as a Potential Biomarker for Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) is a life threatening condition with high morbidity and poor life expectancy. The pathology of PAH is characterised by the loss of small arteries in the lung secondary to medial thickening. Current treatments fail to reverse the disease, and clinical assessment does not always reflect local pathogenesis within the pulmonary circulation. We have previously reported that key pathways associated with PAH converge upon and up-regulate osteoprotegerin (OPG). We have also shown that OPG induces proliferation and migration of PA-SMC in vitro, suggesting an important role in PAH pathogenesis. OPG is a secreted molecule that also interacts with Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL). There is emerging evidence to suggest that TRAIL may also play an important role in disease pathogenesis. We hypothesised that circulating levels of OPG and TRAIL would provide a much-needed biomarker for PAH. The levels of OPG and TRAIL were measured in serum obtained from patients with IPAH, chronic thromboembolic pulmonary hypertension (CTEPH) (pre- & post- endarterectomy), acute coronary syndrome, stable angina and appropriate controls under ethical approval from both Sheffield Teaching Hospitals and Papworth Hospital Foundation Trusts, UK. Levels of OPG, TRAIL and the OPG/TRAIL ratio were then compared with clinical assessments. OPG expression was significantly increased, and TRAIL was significantly decreased in serum from patients with IPAH compared to all other groups (P<0.0001, n=37–76). IPAH patients had significantly higher OPG/TRAIL than either control, or other disease groups, which correlated with Cardiac Index (p<0.0001, R=0.62) and Right Atrial Pressure (p<0.05, R=0.43) but not mean pulmonary artery pressure or 6 minute walk test. OPG was significantly lower in CTEPH patients at 3 months following endarterectomy but there was no significant difference in the levels of TRAIL. Based upon these data, the OPG/TRAIL ratio may be a useful new biomarker for tracking PAH pathogenesis. Combining the two molecules may provide greater power to distinguish PAH pathogenesis. Further work is clearly required to consider other associated PAH groups, and effect of treatments in a larger cohort of patients.