Increased ADORA2B Expression Correlates with Mean Pulmonary Arterial Pressure in Idiopathic Pulmonary Fibrosis

2013 
Purpose Idiopathic pulmonary fibrosis (IPF) is often accompanied by pulmonary hypertension (PH), a mortality predictor leading to increased vascular remodeling, right-heart failure and death. Studies have shown that adenosine A2B receptor (ADORA2B) is elevated after tissue injury and it participates in wound healing and tissue remodeling responses. We aimed to show whether mean pulmonary arterial pressure (mPAP) correlated with pulmonary function tests (PFTs) and increased expression of mediators involved in the disease progression. Methods and Materials A retrospective review on 30 patients on post-lung transplantation with IPF where native lung was collected from 02/2011 to 09/2012. Results of PFTs and mPAP were collected. RNA and protein were isolated for qRT-PCR and western blot from frozen lung explant samples. Controls were 18srRNA and β-actin. Linear regression and Pearson’s correlation between transcript levels and mPAP were analyzed. p Results 12/30 presented with PH (IPF+PH group); 63% male; 60% Caucasian. Linear regression analysis demonstrates no association between PFTs or Collagen I (Col1A1 transcript) levels and mPAP values. mPAP compared to FVC%, TLC%, DLCO% and FEV1% showed no statistical significance. When mPAP was compared to ADORA2B expression levels, we found a significant correlation (p=0.0373, r2 0.1685) suggesting a link between heightened ADORA2B expression levels and elevated mPAP. [ figure 1 ] Western blot corroborated by showing heightened ADORA2B protein levels in IPF+PH. Conclusions Results demonstrate a direct positive correlation between ADORA2B and mPAP in patients with IPF; pointing to a role for ADORA2B in the pathophysiology of PH in IPF that could lead to new therapies.
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