Down Regulation of Angiotensin II Receptor Type 1 (AGTR1) Contrast with Up Regulation of Type 2 (AGTR2) in Idiopathic Pulmonary Fibrosis
Edwin R Parra, Aline DP Ruppert, Maristela P Rangel, Vera L Capelozzi. University of São Paulo Medical School, São Paulo, Brazil
Background: Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia. IPF represents a progressive and lethal disorder and is of major concern due to its unresolved pathogenesis and limited responsiveness to currently available therapies. IPF is characterized by alveolar injury, fibroblast proliferation and extracellular matrix (ECM) accumulation with severe loss of respiratory function. Angiotensin II (ANGII) signaling, mediated via angiotensin II receptor type 1 (AGTR1) or type 2 (AGTR2), controls tissue remodeling in fibrosis, but the relevance of AGTR2 and AGTR1 remains elusive.
Design: Twenty-seven patients with biopsy-proven IPF disease with pulmonary evaluation by high-resolution computed tomography (HRCT) and pulmonary function tests were studied. Ten normal lung tissues (NLT) were included with controls. AGTR1 and AGTR2 in lung parenchyma were detected by immunohistochemistry and quantified by histomorphometry.
Results: Quantitative analysis revealed a significant increase of AGTR2 expression in epithelial, endothelial and fibroblastic cells from patients with IPF when compared to NLT group. In contrast, AGTR1 expression levels are decreased in these cells from patients with IPF when compared with NTL. Pulmonary function tests no showed correlation with expression of AGTR1 or AGTR2. The median follow-up was 42.70 months. Ten patients were still alive, 17 died from causes related to IPF. Kaplan Meier curve, showed that the 5-year survival rate in patients with <0.05% of AGTR1 levels was 58.20% versus 24.66% in the group with ≥ 0.05% of AGTR1 levels (p < 0.05).
Conclusions: In summary, we demonstrated increased expression of AGTR2 and decreased expression of AGTR1 in lung tissues from patients with IPF suggesting that they may be promising markers of prognosis in these patients.
Financial Support: FAPESP, CNPq.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 288, Tuesday Afternoon