Exosomally derived Y RNA fragment alleviates hypertrophic cardiomyopathy in transgenic mice.

Molecular Therapy. Nucleic Acids
Feng HuangGeoffrey de Couto

Abstract

Cardiosphere-derived cell exosomes (CDCexo) and YF1, a CDCexo-derived non-coding RNA, elicit therapeutic bioactivity in models of myocardial infarction and hypertensive hypertrophy. Here we tested the hypothesis that YF1, a 56-nucleotide Y RNA fragment, could alleviate cardiomyocyte hypertrophy, inflammation, and fibrosis associated with hypertrophic cardiomyopathy (HCM) in transgenic mice harboring a clinically relevant mutation in cardiac troponin I (cTnIGly146). By quantitative PCR, YF1 was detectable in bone marrow, spleen, liver, and heart 30 min after intravenous (i.v.) infusion. For efficacy studies, mice were randomly allocated to receive i.v. YF1 or vehicle, monitored for ambulatory and cardiac function, and sacrificed at 4 weeks. YF1 (but not vehicle) improved ambulation and reduced cardiac hypertrophy and fibrosis. In parallel, peripheral mobilization of neutrophils and proinflammatory monocytes was decreased, and fewer macrophages infiltrated the heart. RNA-sequencing of macrophages revealed that YF1 confers substantive and broad changes in gene expression, modulating pathways associated with immunological disease and inflammatory responses. Together, these data demonstrate that YF1 can reverse hypertrophic and fibr...Continue Reading

References

Oct 12, 2013·Pflügers Archiv : European journal of physiology·Ana M Pajor
Jun 18, 2014·Stem Cell Reports·Ahmed Gamal-Eldin IbrahimEduardo Marbán
Jul 28, 2015·The Journal of Clinical Investigation·Geoffrey de CoutoEduardo Marbán
Apr 16, 2017·Circulation·Geoffrey de CoutoEduardo Marbán
Sep 12, 2017·The Journal of Clinical Investigation·Hadi KhalilJeffery D Molkentin
Jan 4, 2018·Blood Advances·Cesar Nombela-Arrieta, Markus G Manz
Feb 12, 2019·Nature Biomedical Engineering·Eduardo Marbán
Apr 13, 2019·Annual Review of Genomics and Human Genetics·Raquel YottiJonathan G Seidman
Apr 21, 2019·Progress in Cardiovascular Diseases·Zackary D Goff, Hugh Calkins
Aug 23, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Geoffrey de CoutoEduardo Marbán
Nov 28, 2019·Nature·Ronald J VagnozziJeffery D Molkentin
Dec 21, 2019·Experimental & Molecular Medicine·Geoffrey de Couto

❮ Previous
Next ❯

Software Mentioned

Torrent Suite
GraphPad Prism
ImageJ

Related Concepts

Related Feeds

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.