Abstract 13449: Oncostatin M is Elevated in the Plasma of Patients With Pulmonary Arterial Hypertension, but Not in Patients With Ischemic Heart Disease or Dilated Cardiomyopathy: Insight Into Mechanisms in vitro
Recently the macrophage and T-lymphocyte specific inflammatory cytokine Oncostatin M (OSM) has been identified to be a factor in mediating proliferation, migration and extracellular matrix protein synthesis. The purpose of this study was to investigate if elevated levels of plasma OSM were associated with clinical conditions resulting from vascular disease. We compared plasma OSM concentrations from patients with ischemic heart disease (IHD), dilated cardiomyopathy (DCM), and pulmonary arterial hypertension (PAH). In addition, we conducted in vitro studies to further investigate potential mechanisms of effect. We collected the plasma from 93 patients that came into the University Hospital of Heidelberg during the winter and spring of 2010 (16 controls, 28 IHD, 27 DCM, and 22 PAH). We measured OSM levels by ELISA and identified that OSM was elevated in patients with PAH compared to healthy controls, IHD, and DCM patients (linear regression, coefficient=149.5, 95% CI 53.1-245.9; P=0.003). The mean OSM plasma concentration in patients with PAH was 161 pg/ml (SE±87pg/ml) while IHD and DCM means were near zero. In two patients with PAH, OSM plasma concentrations were above 1200pg/ml. To further investigate potential mechanisms, we identified that OSM drives cell migration of mouse vascular smooth muscle cells (MOVAS) as well as human umbilical vein endothelial cells (HUVEC) measured by scratch assay, but does not itself increase cell proliferation. We also identified that OSM rapidly increases the expression of the transcription factor Egr-1 in MOVAS and increases endothelin-1 production in HUVEC. These findings provide an insight into the potential role of OSM to accelerate the development of PAH. Findings from our group and others further suggest that OSM may be an important therapeutic target in treating vascular diseases.
- © 2011 by American Heart Association, Inc.