A Peripheral Blood Signature of Vasodilator-Responsive Pulmonary Arterial Hypertension | Journal Scan

Study Questions:

While uncommon, vasodilator responsive pulmonary artery hypertension (V-PAH) has a pronounced response to calcium channel blockers and better survival than nonresponsive PAH (VN-PAH). Does VR-PAH have a different molecular etiology from VN-PAH that can be detected in the peripheral blood?

Methods:

Microarrays of cultured lymphocytes from VR-PAH and VN-PAH patients cared for at Vanderbilt University were performed with quantitative polymerase chain reaction (PCR) on peripheral blood to find the genes that displayed the greatest intergroup differences in expression. A decision tree to identify VR-PAH patients was based on the results with validation in a second VR-PAH cohort at the University of Chicago.

Results:

Broad differences in gene expression patterns were found on microarray analysis including cell-cell adhesion factors, cytoskeletal and rho/GTPase genes. 13/25 genes tested in whole blood were significantly different: EPDR1, DSG2, SCD5, P2RY5, MGAT5, RHOQ, UCHL1, NF652, RALGPS2, TPD52, MKNL1, RAPGEF2, and PIAS1. Seven decision trees were built using expression levels of two genes as the primary genes: DSG2, a desmosomal cadherin involved in Wnt/ß-catenin signaling, and RHOQ, which encodes a cytoskeletal protein involved in insulin-mediated signaling.

Conclusions:

The authors concluded that VR-PAH and VN-PAH can be differentiated using RNA expression patterns in peripheral blood. These differences may reflect different molecular etiologies of the two PAH phenotypes. This biomarker methodology may identify PAH patients that have a favorable treatment response.

Perspective:

While presently a proof of concept, the findings suggest that serum biomarkers may provide information on the pathogenesis of PAH and other forms of pulmonary hypertension, and potentially help in the development of new and specific targets for treatment and prevention.

Clinical Topics: Heart Failure and Cardiomyopathies, Pulmonary Hypertension and Venous Thromboembolism, Heart Failure and Cardiac Biomarkers, Pulmonary Hypertension

Keywords: Biological Markers, Calcium Channel Blockers, Decision Trees, Desmosomal Cadherins, GTP Phosphohydrolases, Hypertension, Pulmonary, Lymphocytes, Microarray Analysis, Polymerase Chain Reaction, Signal Transduction, Vasodilator Agents


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