Angiotensin II-Induced End-Organ Damage in Mice Is Attenuated by Human Exosomes and by an Exosomal Y RNA Fragment.
Angiotensin II-Induced End-Organ Damage in Mice Is Attenuated by Human Exosomes and by an Exosomal Y RNA Fragment.
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DOI：
10.1161/hypertensionaha.118.11239
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发表时间：
2018-08
期刊：
影响因子：
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通讯作者：
Marbán E
中科院分区：
文献类型：
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作者：
Cambier L;Giani JF;Liu W;Ijichi T;Echavez AK;Valle J;Marbán E
高血压常导致心血管疾病（CVD）和肾功能障碍。心球源性细胞（CDC-exo）分泌的外泌体及其最丰富的小RNA成分，Y RNA片段EV-YF1，在心肌梗死后发挥治疗作用。在这里，我们研究了单独给药的CDC-exo和EV-YF1在慢性血管紧张素（Ang） II诱导的心脏肥大和肾损伤模型中的作用。Ang II治疗2周后，眼眶后给药多剂CDC-exo或EV-YF1。Ang II输注诱导收缩压升高，不受CDC-exo或EV-YF1的影响。超声心动图证实Ang II输注导致心脏肥厚。CDC-exo和EV-YF1均能减轻心脏肥厚，减轻心脏炎症和纤维化。此外，CDC-exo和EV-YF1均能改善肾功能，减轻肾脏炎症和纤维化。CDC-exo和EV-YF1的有益作用与血浆、心脏、脾脏和肾脏中抗炎细胞因子IL-10的表达变化有关。综上所述，输注CDC-exo或EV-YF1减轻了Ang II输注引起的心脏肥大和肾脏损伤，而不影响血压，并改变了IL-10的表达。外泌体及其定义的非编码RNA含量可能代表高血压相关心血管和肾脏损害的潜在新治疗方法。
Hypertension often leads to cardiovascular disease (CVD) and kidney dysfunction. Exosomes secreted from cardiosphere-derived cells (CDC-exo) and their most abundant small RNA constituent, the Y RNA fragment EV-YF1, exert therapeutic benefits after myocardial infarction. Here, we investigated the effects of CDC-exo and EV-YF1, each administered individually, in a model of cardiac hypertrophy and kidney injury induced by chronic infusion of angiotensin (Ang) II. After 2 weeks of Ang II, multiple doses of CDC-exo or EV-YF1 were administered retro-orbitally. Ang II infusion induced an elevation in systolic blood pressure that was not affected by CDC-exo or EV-YF1. Echocardiography confirmed that Ang II infusion led to cardiac hypertrophy. CDC-exo and EV-YF1 both attenuated cardiac hypertrophy and reduced cardiac inflammation and fibrosis. In addition, both CDC-exo and EV-YF1 improved kidney function, and diminished renal inflammation and fibrosis. The beneficial effects of CDC-exo and EV-YF1 were associated with changes in the expression of the anti-inflammatory cytokine IL-10 in plasma, heart, spleen and kidney. In summary, infusions of CDC-exo or EV-YF1 attenuated cardiac hypertrophy and renal injury induced by Ang II infusion, without affecting blood pressure, in association with altered IL-10 expression. Exosomes and their defined noncoding RNA contents may represent potential new therapeutic approaches for hypertension-associated cardiovascular and renal damage.