Key result
Intravenous administration of iPS-MSC-derived extracellular vesicles significantly attenuated ageing-related arterial stiffness and hypertension in old mice.
Why the study?
The prevalence of arterial stiffness and hypertension increases with age, prompting investigation into the effect of induced pluripotent mesenchymal stem cell-derived extracellular vesicles on ageing-associated arterial stiffness and hypertension.
Do induced pluripotent mesenchymal stem cell-derived extracellular vesicles reduce arterial stiffness and hypertension in old male C57BL/6 mice?
Do induced pluripotent mesenchymal stem cell-derived extracellular vesicles reduce arterial stiffness and hypertension in old male C57BL/6 mice?
p-value: p=<0.05
iPS-MSC-derived extracellular vesicles mitigate ageing-associated vascular endothelial dysfunction, arterial stiffness, and hypertension in a mouse model, suggesting therapeutic potential for ageing-related vascular diseases.
Supports EV therapy investigation for vascular ageing in mice; leaves open human translation and requires prospective trials.
The prevalence of arterial stiffness and hypertension increases with age. This study investigates the effect of induced pluripotent mesenchymal stem cell‐derived extracellular vesicles (EVs) on ageing‐associated arterial stiffness and hypertension. EVs were collected and purified from induced pluripotent stem cell‐derived mesenchymal stem cells (iPS‐MSCs). Young and old male C57BL/6 mice were used. Mice in the EVs group were injected via tail vein once a week for four weeks (18 x 10 6 EVs/mouse/injection). Blood pressure (BP) was measured using the tail‐cuff method and validated by direct cannulation. Pulse wave velocity (PWV) was measured using a Doppler workstation. PWV and BP were increased significantly in the old mice, indicating arterial stiffness and hypertension. Intravenous administration of EVs significantly attenuated ageing‐related arterial stiffness and hypertension, while enhancing endothelium‐dependent vascular relaxation and arterial compliance in the old EVs mice. Elastin degradation and collagen I deposition (fibrosis) were increased in aortas of the old mice, but EVs substantially improved ageing‐associated structural remodelling. Mechanistically, EVs abolished downregulation of sirtuin type 1 (SIRT1), and endothelial nitric oxide synthase (eNOS) protein expression in aortas of the older mice. In cultured human aortic endothelial cells, EVs promoted the expression of SIRT1, AMP‐activated protein kinase alpha (AMPKα), and eNOS. In conclusion, iPS‐MSC‐derived EVs attenuated ageing‐associated vascular endothelial dysfunction, arterial stiffness, and hypertension, likely via activation of the SIRT1‐AMPKα‐eNOS pathway and inhibition of MMPs and elastase. Thus, EVs mitigate arterial ageing. This finding also sheds light into the therapeutic potential of EVs for ageing‐related vascular diseases. Abbreviations EV: Extracellular vesicles; iPS: induced pluripotent stem cell; MSC: mesenchymal stem cell; AMPKα: AMP activated protein kinase α; eNOS: endothelial nitric oxide synthase; Sirt1: sirtuin 1; JNC7: Seventh Report of the Joint National Committee; CVD: cardiovascular disease; PWV: pulse wave velocity; BP: blood pressure; SNP: sodium nitroprusside
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Feng et al. (2020) studied Ageing-associated arterial stiffness and hypertension (n=20). iPS-MSC-derived extracellular vesicles (EVs) vs. Phosphate buffered solution (PBS) was evaluated on Blood pressure and Pulse wave velocity (PWV) (p=<0.05). Intravenous administration of iPS-MSC-derived extracellular vesicles significantly attenuated ageing-related arterial stiffness and hypertension in old mice.
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