Fanny Loisel1, Bastien Provost2, Julien Guihaire3, David Boulate4, Nassim Arouche5, Myriam Amsallem2, Jennifer Arthur-Ataam2, Benoît Decante2, Peter Dorfmüller6, Elie Fadel7, Georges Uzan5, Olaf Mercier8. 1. Research and Innovation Unit, Inserm UMR-S 999, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France; Inserm 1197 Research Unit, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France. 2. Research and Innovation Unit, Inserm UMR-S 999, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France. 3. Research and Innovation Unit, Inserm UMR-S 999, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France; Department of Cardiac Surgery, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France. 4. Research and Innovation Unit, Inserm UMR-S 999, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France; Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France. 5. Inserm 1197 Research Unit, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France. 6. Research and Innovation Unit, Inserm UMR-S 999, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France; Department of Pathology, Marie Lannelongue Hospital, Le Plessis Robinson, France. 7. Research and Innovation Unit, Inserm UMR-S 999, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France; Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France; Paris-Sud University and Paris-Saclay University, School of Medicine, Kremlin-Bicêtre, France. 8. Research and Innovation Unit, Inserm UMR-S 999, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France; Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Marie Lannelongue Hospital, Univ Paris Sud, Paris-Saclay University, Le Plessis Robinson, France; Paris-Sud University and Paris-Saclay University, School of Medicine, Kremlin-Bicêtre, France. Electronic address: o.mercier@ccml.fr.
Abstract
BACKGROUND: Right ventricular (RV) failure is the main prognostic factor in pulmonary hypertension, and ventricular capillary density (CD) has been reported to be a marker of RV maladaptive remodeling and failure. Our aim was to determine whether right intracoronary endothelial progenitor cell (EPC) infusion can improve RV function and CD in a piglet model of chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: We compared 3 groups: sham (n = 5), CTEPH (n = 6), and CTEPH with EPC infusion (CTEPH+EPC; n = 5). After EPC isolation from CTEPH+EPC piglet peripheral blood samples at 3 weeks, the CTEPH and sham groups underwent right intracoronary infusion of saline, and the CTEPH+EPC group received EPCs at 6 weeks. RV function, pulmonary hemodynamics, and myocardial morphometry were investigated in the animals at 10 weeks. RESULTS: After EPC administration, the RV fractional area change increased from 32.75% (interquartile range [IQR], 29.5%-36.5%) to 39% (IQR, 37.25%-46.50%; P = .030). The CTEPH+EPC piglets had reduced cardiomyocyte surface areas (from 298.3 μm2 [IQR, 277.4-335.3 μm2] to 234.6 μm2 (IQR, 211.1-264.7 μm2; P = .017), and increased CD31 expression (from 3.12 [IQR, 1.27-5.09] to 7.14 [IQR, 5.56-8.41; P = .017). EPCs were found in the RV free wall at 4 and 24 hours after injection but not 4 weeks later. CONCLUSIONS: Intracoronary infusion of EPC improved RV function and CD in a piglet model of CTEPH. This novel cell-based therapy might represent a promising RV-targeted treatment in patients with pulmonary hypertension.
BACKGROUND: Right ventricular (RV) failure is the main prognostic factor in pulmonary hypertension, and ventricular capillary density (CD) has been reported to be a marker of RV maladaptive remodeling and failure. Our aim was to determine whether right intracoronary endothelial progenitor cell (EPC) infusion can improve RV function and CD in a piglet model of chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: We compared 3 groups: sham (n = 5), CTEPH (n = 6), and CTEPH with EPC infusion (CTEPH+EPC; n = 5). After EPC isolation from CTEPH+EPC piglet peripheral blood samples at 3 weeks, the CTEPH and sham groups underwent right intracoronary infusion of saline, and the CTEPH+EPC group received EPCs at 6 weeks. RV function, pulmonary hemodynamics, and myocardial morphometry were investigated in the animals at 10 weeks. RESULTS: After EPC administration, the RV fractional area change increased from 32.75% (interquartile range [IQR], 29.5%-36.5%) to 39% (IQR, 37.25%-46.50%; P = .030). The CTEPH+EPC piglets had reduced cardiomyocyte surface areas (from 298.3 μm2 [IQR, 277.4-335.3 μm2] to 234.6 μm2 (IQR, 211.1-264.7 μm2; P = .017), and increased CD31 expression (from 3.12 [IQR, 1.27-5.09] to 7.14 [IQR, 5.56-8.41; P = .017). EPCs were found in the RV free wall at 4 and 24 hours after injection but not 4 weeks later. CONCLUSIONS: Intracoronary infusion of EPC improved RV function and CD in a piglet model of CTEPH. This novel cell-based therapy might represent a promising RV-targeted treatment in patients with pulmonary hypertension.
Authors: Kelly Stam; Zongye Cai; Nikki van der Velde; Richard van Duin; Esther Lam; Jolanda van der Velden; Alexander Hirsch; Dirk J Duncker; Daphne Merkus Journal: J Physiol Date: 2019-07-25 Impact factor: 5.182