Key result
CDC-exo and EV-YF1 attenuated cardiac hypertrophy and renal injury induced by Ang II infusion in mice, without affecting blood pressure.
Why the study?
Do CDC-exo or EV-YF1 attenuate cardiac hypertrophy and renal injury in mice with Angiotensin II-induced end-organ damage?
Do CDC-exo or EV-YF1 attenuate cardiac hypertrophy and renal injury in mice with Angiotensin II-induced end-organ damage?
CDC-exo and EV-YF1 attenuate Angiotensin II-induced cardiac hypertrophy and renal injury in mice, suggesting a potential noncoding RNA-based therapeutic approach for hypertension-associated end-organ damage.
Hypothesis-generating for exosome therapies targeting hypertensive organ damage; clinical translation requires prospective validation.
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.
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Cambier et al. (2018) studied Angiotensin II-induced cardiac hypertrophy and kidney injury. CDC-exo or EV-YF1 was evaluated on Cardiac hypertrophy and kidney injury. CDC-exo and EV-YF1 attenuated cardiac hypertrophy and renal injury induced by Ang II infusion in mice, without affecting blood pressure.
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