Key result
Extracellular vesicles from monocrotaline-injured mice induced pulmonary hypertension when injected into healthy mice, increasing right ventricular-to-body weight ratio.
Why the study?
Do extracellular vesicles from monocrotaline-injured mice induce pulmonary hypertensive changes in healthy mice?
Do extracellular vesicles from monocrotaline-injured mice induce pulmonary hypertensive changes in healthy mice?
Answers are grounded in this paper and cite their sources.
Extracellular vesicles from monocrotaline-injured mice can directly induce pulmonary hypertension and vascular remodeling in healthy mice, suggesting EVs actively participate in PAH pathogenesis.
AIMS: Circulating endothelium-derived extracellular vesicles (EV) levels are altered in pulmonary arterial hypertension (PAH) but whether they are biomarkers of cellular injury or participants in disease pathogenesis is unknown. Previously, we found that lung-derived EVs (LEVs) induce bone marrow-derived progenitor cells to express lung-specific mRNA and protein. In this study, we sought to determine whether LEV or plasma-derived EV (PEV) alter pulmonary vascular endothelial or marrow progenitor cell phenotype to induce pulmonary vascular remodelling. METHODS AND RESULTS: LEV, PEV isolated from monocrotaline (MCT-EV)- or vehicle-treated mice (vehicle-EV) were injected into healthy mice. Right ventricular (RV) hypertrophy and pulmonary vascular remodelling were assessed by RV-to-body weight (RV/BW) and blood vessel wall thickness-to-diameter (WT/D) ratios. RV/BW, WT/D ratios were elevated in MCT- vs. vehicle-injected mice (1.99 ± 0.09 vs. 1.04 ± 0.09 mg/g; 0.159 ± 0.002 vs. 0.062 ± 0.009%). RV/BW, WT/D ratios were higher in mice injected with MCT-EV vs. mice injected with vehicle-EV (1.63 ± 0.09 vs. 1.08 ± 0.09 mg/g; 0.113 ± 0.02 vs. 0.056 ± 0.01%). Lineage-depleted bone marrow cells incubated with MCT-EV and marrow cells isolated from mice infused with MCT-EV had greater expression of endothelial progenitor cell mRNAs and mRNAs abnormally expressed in PAH than cells incubated with vehicle-EV or isolated from vehicle-EV infused mice. MCT-EV induced an apoptosis-resistant phenotype in murine pulmonary endothelial cells and lineage-depleted bone marrow cells incubated with MCT-EV induced pulmonary hypertension when injected into healthy mice. CONCLUSIONS: EV from MCT-injured mice contribute to the development of MCT-induced pulmonary hypertension. This effect may be mediated directly by EV on the pulmonary vasculature or by differentiation of bone marrow cells to endothelial progenitor cells that induce pulmonary vascular remodelling.
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Aliotta et al. (2013) studied Pulmonary arterial hypertension. Extracellular vesicles from monocrotaline-treated mice (MCT-EV) vs. Extracellular vesicles from vehicle-treated mice (vehicle-EV) was evaluated on Right ventricular-to-body weight (RV/BW) ratio. Extracellular vesicles from monocrotaline-injured mice induced pulmonary hypertension when injected into healthy mice, increasing right ventricular-to-body weight ratio.
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