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Section:ChooseTop of pageAbstract <<Normal Lung AgingCellular SenescenceSenescence-associated Sec...Phosphoinositide-3-Kinase...Reduced Antiaging Molecul...Key Role of MicroRNAExtracellular Vesicles as...Implications for TherapyConclusionsReferencesCITING ARTICLES
The QVDA highlights the superior performance of the Myval THV series compared to the Evolut THV series, with the lowest rate of moderate/severe RF among the three THV series, and could be used with echocardiography to help in detecting cases with none/trace AR.
<h3>Background</h3> COPD is associated with cellular senescence and fibrosis. Extracellular vesicles (EVs) are membrane-derived vesicles involved in intercellular communication. EVs contain miRNAs, mRNA and proteins and have been implicated in COPD to induce senescence and the transition of fibroblast to myofibroblasts. This study examined whether EVs derived from COPD fibroblasts drive senescence in healthy recipient fibroblasts. Changes in expression of p21<sup>CIP1</sup> and alpha-smooth muscle actin (αSMA) were chosen as markers of senescence and transition of fibroblasts to myofibroblasts respectively. <h3>Methods</h3> Large EVs, and small EVs were isolated from media from non-smoker (NS) and COPD fibroblasts cultured with or without H<sub>2</sub>O<sub>2.</sub> EVs were labelled with phk67 and uptake measured by flow cytometry. Healthy recipient fibroblasts were cultured with EVs or EV-free media for 24h and 48h and protein expression of p21<sup>CIP1</sup> and αSMA measured using western blots and CXCL8 release by ELISA. <h3>Results</h3> There was a time-dependent uptake of EVs into recipient cells with no difference between EVs from control or COPD fibroblasts with 91.8 ± 3.8<b>%</b> of recipient cells phk67 positive by 48h (n=4). Incubation of recipient fibroblasts (n=2–5) with large EVs from either non-smokers or COPD subjects did not alter the expression of p21<sup>CIP1</sup> or αSMA at 24h. Similarly large EVs from fibroblasts exposed to H<sub>2</sub>O<sub>2</sub> had no effect on these markers in recipient cells. By contrast, at 48h (figure 1), small EVs from COPD cells showed a trend to increased expression of p21<sup>CIP1</sup> and EVs from both non-smokers and COPD subjects increased expression of αSMA. Incubation of recipient cells with large EVs from non-smoker fibroblasts that had been cultured with or without H<sub>2</sub>O<sub>2</sub> increased release of CXCL8 (0.36±0.15ng/ml to 5.43±3.92ng/ml and 5.44±5.23ng/ml respectively) and small EVs from COPD fibroblasts induced CXCL8 release at 48h (0.36±0.15ng/ml to 3.75±3.16ng/ml). <h3>Conclusions</h3> Large and small EVs tend to increase the expression of p21<sup>CIP1</sup> and αSMA in recipient fibroblasts. These results are confirmed by the uptake analysis showing that maximum uptake of EVs from both NS and COPD fibroblasts is reached after 48h. Altogether, these data suggest that EVs participate in COPD pathophysiology by spreading senescence in recipient fibroblasts.
No abstract is provided for this article.
Adenosine 5’-triphosphate (ATP) is found in every cell of the body where it plays a critical role in cellular metabolism and energetics. ATP is released from cells under physiologic and pathophysiologic conditions; extracellular ATP acts as an autocrine and paracrine agent. Its effects on targeted cells are mediated by subtypes of purinergic receptors (P2R). In the lungs, relatively large amounts of ATP are released under inflammatory conditions. Extracellular ATP triggers a central vagal reflex by activating purinergic receptor P2XR localized on pulmonary vagal sensory nerve terminals. This results in cough, bronchoconstriction and the release of pro-inflammatory neuropeptides via axon reflex. COPD patients manifest higher sensetivity to aerosolized ATP than healthy subjects, and the levels of ATP in COPD patients’ lungs are 3x that found in healthy subjects. This review succinctly details (i) the sources amd mechanisms of ATP’s release into the extracellular space, (ii) the ways extracellular ATP is eliminated, (iii) the deleterious effects of ATP in the lungs in general and in COPD in particular, and (iv) the rationale for the blockade of these actions of ATP in the lungs as a novel therapeutic approach in the management of COPD patients.