Circulating Extracellular Vesicles in Normotension Restrain Vasodilation in Resistance Arteries
Circulating Extracellular Vesicles in Normotension Restrain Vasodilation in Resistance Arteries
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DOI：
10.1161/hypertensionaha.119.13363
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发表时间：
2020-01-01
期刊：
影响因子：
8.3
通讯作者：
Erdbruegger, Uta
中科院分区：
文献类型：
--
作者：
Good, Miranda E.;Musante, Luca;Erdbruegger, Uta
细胞外囊泡（EVs）已被描述为高血压血管功能障碍的新型生物标志物和生物激活剂。然而，EV影响血管功能的机制尚不清楚。为了检测EV对内皮依赖性血管舒张（乙酰胆碱）的影响，我们使用低离心速度（17 000 g）从血小板贫乏的血浆中分离循环EV，并从12周龄血压正常的WKY（Wistar-Kyoto大鼠）和SHR（自发性高血压大鼠）中分离肠系膜阻力动脉。在压力肌描记器上对动脉进行插管，并将EV添加到血管腔和循环浴中。我们发现，来自血压正常的WKY的循环EV减少了血压正常的WKY动脉的血管舒张，但对高血压的SHR动脉没有影响。相比之下，高血压SHR的EV未能减少WKY和SHR动脉的血管舒张。来自血压正常的WKY的EV对血管舒张的抑制作用可能是通过抑制eNOS（内皮NO合酶）介导的，因为添加L-硝基精氨酸甲酯没有提供任何累加效应。此外，来自血压正常的6周龄SHR（SHR尚未发展为高血压的年龄）的循环EV对血管舒张具有类似的抑制作用。除此之外，去脂处理并没有改变WKY的EV的抑制作用，但却恢复了SHR的EV的抑制作用。最后，来自血压正常的人的EV也抑制了血压正常的小鼠动脉的血管舒张，这在来自高血压的人的EV中没有观察到。总之，我们的数据支持EV的血管活性作用在高血压中改变。
Extracellular vesicles (EVs) have been described as novel biomarkers and bioactivators in vascular dysfunction in hypertension. However, the mechanism(s) by which EVs affect vascular function is unknown. To examine the effects of EVs on endothelial-dependent vasodilation (acetylcholine), we isolated circulating EVs from platelet-poor plasma using a low centrifugation speed (17 000g) and mesenteric resistance arteries from 12-week-old normotensive WKYs (Wistar-Kyoto rats) and SHRs (spontaneously hypertensive rats). Arteries were cannulated on a pressure myograph, and EVs were added to the vessel lumen and circulating bath. We found that circulating EVs from normotensive WKY reduced vasodilation of normotensive WKY arteries but had no effect on hypertensive SHR arteries. In contrast, EVs from hypertensive SHR failed to reduce vasodilation of arteries from both WKY and SHR. The restraining effect on vasodilation by EVs from normotensive WKY may be mediated by inhibition of eNOS (endothelial NO synthase), as addition of L-nitro-arginine methyl ester did not provide any additive effect. Moreover, circulating EVs from normotensive 6-week-old SHR-an age where SHRs have not yet developed hypertension-had similar restraining effect on vasodilation. In addition, delipidation of EVs did not alter the restraining effect of EVs from WKY but did restore the restraining effect of EVs from SHR. Finally, EVs from normotensive humans also restrained vasodilation of normotensive mouse arteries-an effect not observed in EVs from hypertensive humans. Taken together, our data support a vasoactive role of EVs that is altered in hypertension.