Angiotensin II–Induced End-Organ Damage in Mice Is Attenuated by Human Exosomes and by an Exosomal Y RNA Fragment. Issue 2 (August 2018)

• Record Type: Journal Article
• Authors: Cambier, Linda; Giani, Jorge F.; Liu, Weixin; Ijichi, Takeshi; Echavez, Antonio K.; Valle, Jackelyn; Marbán, Eduardo
• Is Part Of: Hypertension. Volume 72:Issue 2(2018:Aug.)
• Publication Date: 2018-08
• Subjects: angiotensin II -- exosomes -- kidney -- macrophages -- risk factors; Hypertension -- Periodicals; Hypertension -- Treatment -- Periodicals; 616.132005
• DOI: 10.1161/HYPERTENSIONAHA.118.11239
• Languages: English
• ISSNs: 0194-911X

Abstract

Abstract : Hypertension often leads to cardiovascular disease 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 Ang (angiotensin) 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 (interleukin)-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. Abstract : Supplemental Digital Content is available in the text.