Outgrowth, proliferative speed and angiogenic capacity of Endothelial Colony Forming Cells (ECFC) correlate with disease severity and right ventricular (RV) adaptation in Pulmonary Arterial Hypertension (PAH) patients
J. Smits (Amsterdam, Netherlands), D. Tasev (Amsterdam, Netherlands), R. Szulcek (Amsterdam, Netherlands), S. Andersen (Aarhus, Denmark), S. Ringaard (Aarhus, Denmark), J. Hyldebradt (Aarhus, Denmark), A. Andersen (Aarhus, Denmark), A. Vonk-Noordegraaf (Amsterdam, Netherlands), P. Koolwijk (Amsterdam, Netherlands), H. Bogaard (Amsterdam, Netherlands)
Source: International Congress 2018 – Pathobiology of pulmonary hypertension
Session: Pathobiology of pulmonary hypertension
Session type: Poster Discussion
Number: 3934
Disease area: Pulmonary vascular diseases
Abstract Pulmonary arterial hypertension (PAH) is associated with angioproliferation in the lung and, paradoxically, vascular rarefaction in the right ventricle (RV). Endothelial colony forming cells (ECFC) are angioproliferative endothelial cells implicated in tissue repair. Here we investigated wether ECFC characteristics correlate with disease severity, pulmonary vascular resistance (PVR) and RV-function.
Methods ECFC were collected from 36 PAH and 21 healthy donors. Proliferation and angiogenic capacity upon GF stimulation were analyzed. Subsequently, in vitro findings correlated to clinical parameters including PVR, time to clinical worsening (TTCW), mixed venous oxygen saturation (SvO2), RV volumes and ejection fraction (RVEF). In addition, we investigated the effect of PAH ECFC infusion in pulmonary trunk banded rats.
Results ECFCs could be obtained from two thirds of PAH donors. Presence of ECFC outgrowth was associated with a worse clinical profile (RVEF p=0.05, SvO2 p=0.05, TTCW p=0.05). In addition, the number of colonies correlated negatively with SvO2 (R2=0.35, p=0.01). On the contrary, a low proliferative speed of PAH ECFCs was associated with RV dilatation. Transplantation of proliferative, angiogenic PAH ECFC in rats subjected to pulmonary trunk banding, improved vascular density of RV-cardiac tissue, but was not associated with improved RV function.
Conclusion These data suggest circulating ECFC are upregulated in end-stage disease and play a compensatory role in the pressure overloaded RV by improving cardiac muscle vascularity.
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J. Smits (Amsterdam, Netherlands), D. Tasev (Amsterdam, Netherlands), R. Szulcek (Amsterdam, Netherlands), S. Andersen (Aarhus, Denmark), S. Ringaard (Aarhus, Denmark), J. Hyldebradt (Aarhus, Denmark), A. Andersen (Aarhus, Denmark), A. Vonk-Noordegraaf (Amsterdam, Netherlands), P. Koolwijk (Amsterdam, Netherlands), H. Bogaard (Amsterdam, Netherlands). Outgrowth, proliferative speed and angiogenic capacity of Endothelial Colony Forming Cells (ECFC) correlate with disease severity and right ventricular (RV) adaptation in Pulmonary Arterial Hypertension (PAH) patients. 3934
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