Therapeutic Benefit of the Association of Lodenafil with Mesenchymal Stem Cells on Hypoxia-induced Pulmonary Hypertension in Rats
Open Access
- 17 September 2020
- Vol. 9 (9), 2120
- https://doi.org/10.3390/cells9092120
Abstract
Pulmonary arterial hypertension (PAH) is characterized by the remodeling of pulmonary arteries, with an increased pulmonary arterial pressure and right ventricle (RV) overload. This work investigated the benefit of the association of human umbilical cord mesenchymal stem cells (hMSCs) with lodenafil, a phosphodiesterase-5 inhibitor, in an animal model of PAH. Male Wistar rats were exposed to hypoxia (10% O2) for three weeks plus a weekly i.p. injection of a vascular endothelial growth factor receptor inhibitor (SU5416, 20 mg/kg, SuHx). After confirmation of PAH, animals received intravenous injection of 5.105 hMSCs or vehicle, followed by oral treatment with lodenafil carbonate (10 mg/kg/day) for 14 days. The ratio between pulmonary artery acceleration time and RV ejection time reduced from 0.42 ± 0.01 (control) to 0.24 ± 0.01 in the SuHx group, which was not altered by lodenafil alone but was recovered to 0.31 ± 0.01 when administered in association with hMSCs. RV afterload was confirmed in the SuHx group with an increased RV systolic pressure (mmHg) of 52.1 ± 8.8 normalized to 29.6 ± 2.2 after treatment with the association. Treatment with hMSCs + lodenafil reversed RV hypertrophy, fibrosis and interstitial cell infiltration in the SuHx group. Combined therapy of lodenafil and hMSCs may be a strategy for PAH treatment.This publication has 53 references indexed in Scilit:
- Pathology and Pathobiology of Pulmonary HypertensionSeminars in Respiratory and Critical Care Medicine, 2013
- Long-term research of stem cells in monocrotaline-induced pulmonary arterial hypertensionClinical and Experimental Medicine, 2013
- Exosomes Mediate the Cytoprotective Action of Mesenchymal Stromal Cells on Hypoxia-Induced Pulmonary HypertensionCirculation, 2012
- A TRPC6-Dependent Pathway for Myofibroblast Transdifferentiation and Wound Healing In VivoDevelopmental Cell, 2012
- Validation of high-resolution echocardiography and magnetic resonance imaging vs. high-fidelity catheterization in experimental pulmonary hypertensionAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2010
- Is the intravascular administration of mesenchymal stem cells safe?: Mesenchymal stem cells and intravital microscopyMicrovascular Research, 2009
- Increased plasma monocyte chemoattractant protein‐1 level in idiopathic pulmonary arterial hypertensionRespirology, 2006
- Nitric Oxide Inhibits Endothelin-1-Induced Cardiomyocyte Hypertrophy through cGMP-mediated Suppression of Extracellular-Signal Regulated Kinase PhosphorylationMolecular Pharmacology, 2005
- MAPK signal pathways in the regulation of cell proliferation in mammalian cellsCell Research, 2002
- NF-κB Inhibition Ameliorates Angiotensin II–Induced Inflammatory Damage in RatsHypertension, 2000