Peripheral Blood Signature of Vasodilator-Responsive Pulmonary Arterial Hypertension. Issue 4 (27th January 2015)

• Record Type: Journal Article
• Authors: Hemnes, Anna R.; Trammell, Aaron W.; Archer, Stephen L.; Rich, Stuart; Yu, Chang; Nian, Hui; Penner, Niki; Funke, Mitchell; Wheeler, Lisa; Robbins, Ivan M.; Austin, Eric D.; Newman, John H.; West, James
• Is Part Of: Circulation. Volume 131:Issue 4(2015)
• Publication Date: 2015-01-27
• Subjects: Blood -- Circulation -- Periodicals; Cardiovascular system -- Periodicals; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; 616.1
• DOI: 10.1161/CIRCULATIONAHA.114.013317
• Languages: English
• ISSNs: 0009-7322

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background—</title> <p>Heterogeneity in response to treatment of pulmonary arterial hypertension (PAH) is a major challenge to improving outcome in this disease. Although vasodilator-responsive PAH (VR-PAH) accounts for a minority of cases, VR-PAH has a pronounced response to calcium channel blockers and better survival than vasodilator-nonresponsive PAH (VN-PAH). We hypothesized that VR-PAH has a different molecular cause from VN-PAH that can be detected in the peripheral blood.</p> </sec> <sec> <title>Methods and Results—</title> <p>Microarrays of cultured lymphocytes from VR-PAH and VN-PAH patients followed at Vanderbilt University were performed with quantitative polymerase chain reaction performed on peripheral blood for the 25 most different genes. We developed a decision tree to identify VR-PAH patients on the basis of the results with validation in a second VR-PAH cohort from the University of Chicago. We found broad differences in gene expression patterns on microarray analysis including cell-cell adhesion factors and cytoskeletal and rho-GTPase genes. Thirteen of 25 genes tested in whole blood were significantly different: <italic>EPDR1</italic>, <italic>DSG2</italic>, <italic>SCD5</italic>, <italic>P2RY5</italic>, <italic>MGAT5</italic>, <italic>RHOQ</italic>, <italic>UCHL1</italic>, <italic>ZNF652</italic>, <italic>RALGPS2</italic>, <italic>TPD52</italic>, <italic>MKNL1</italic>, <italic>RAPGEF2</italic>, and <italic>PIAS1.</italic> Seven decision trees were built with the use of expression levels of 2 genes as the primary genes: <italic>DSG2</italic>, a desmosomal cadherin involved in Wnt/β-catenin signaling, and <italic>RHOQ</italic>, which encodes a cytoskeletal protein involved in insulin-mediated signaling. These trees correctly identified 5 of 5 VR-PAH patients in the validation cohort.</p> </sec> <sec> <title>Conclusions—</title> <p>VR-PAH and VN-PAH can be differentiated with the use of RNA expression patterns in peripheral blood. These differences may reflect different molecular causes of the 2 PAH phenotypes. This biomarker methodology may identify PAH patients who have a favorable treatment response.</p> </sec> </abstract>