[1875] Biomarker Profile of Pulmonary Vasculature in Subjects with Portopulmonary Hypertension

Nahal Boroumand, Alexander Duarte, Ragai T Meena, Paul J Boor, Abida K Haque. University of Texas Medical Branch, Galveston, TX; Methodist Hospital, Houston, TX

Background: Pulmonary arterial hypertension (PAH) consists of a heterogenous group of conditions characterized by vasoconstriction, vascular remodeling of the small pulmonary arteries and progressive right ventricular failure. PAH associated with portal hypertension or portopulmonary hypertension (PPH) occurs in 4 to 10 % of subjects with liver disease and portal hypertension. The histopathology of the pulmonary vasculature reveals medial hypertrophy, intimal hyperplasia and plexogenic arteriopathy that is similar to idiopathic and congenital heart disease associated PAH. However, the mechanisms leading to PPH are unclear. Several proposed mechanisms include an excess of endothelin and altered estrogen metabolism. The aim of this study was to determine the quantity and location of endothelin (ET), estrogen (ER), and vascular endothelial growth factor (VEGF) receptors in pulmonary vasculature of subjects with PPH.
Design: We reviewed our hospital autopsy data base from 1994 to 2009 and selected subjects with cirrhosis, right ventricular hypertrophy and histopathology associated with PAH. Paraffin embedded lung tissue was sectioned, treated with antigen retrieval, and immunostained for estrogen (ER- α and ER- β), endothelin (ET-A, ET-B) and VEGF. Two pulmonary pathologists independently reviewed the slides and assessed immunostain intensity.
Results: Fifteen subjects with portopulmonary hypertension were identified. Mean age was 48.7 ± 8.8 yrs; 5/15 (33 %) were female. All subjects demonstrated right ventricular enlargement and histology with medial hypertrophy, intimal hyperplasia and plexogenic arteriopathy. Immunohistochemistry revealed ER- α positivity in 0% of the subjects (0/15) in both endothelial and smooth muscle components, whereas ET-B was positive in 100% of the subjects (15/15) in both endothelial and smooth muscle components. ER- β and ET-A were positive approximately in third of the subjects in endothelial cells. VEGF was positive in all subjects in endothelial cells.
Conclusions: In portopulmonary hypertension, endothelin B receptor was present in endothelial and smooth muscle cells of the pulmonary vasculature in all the subjects. While Endothelin A and Estrogen receptors were either absent or very limited. Endothelin1 is a potent vasoconstrictor, and mediator of cells involved in vascular remodelling, while the effects of estrogens on pulmonary vasculature are beneficial, but complex and not fully understood.
Category: Pulmonary

Tuesday, March 5, 2013 1:00 PM

Poster Session IV # 299, Tuesday Afternoon


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