Abstract 11334: Metabolic Labeling and Systemic Tracking of Cardiomyocyte-Derived Exosomal MiRNAs

HomeCirculationAbstract 11334: Metabolic Labeling and Systemic Tracking of Cardiomyocyte-Derived Exosomal MiRNAs Free AccessAbstractAboutSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessAbstractCardiac Development, Structure and FunctionSession Title: Cardiac Regeneration and Repair AbstractsAbstract 11334: Metabolic Labeling and Systemic Tracking of Cardiomyocyte-Derived Exosomal MiRNAs Chaoshan Han, Junjie Yang, qinkun zhang, Hind Lal, Jianyi Zhang and Gangjian Qin Chaoshan HanChaoshan Han Biomedical Engineering, Univ of Alabama at Birmingham, Birmingham, AL Search for more papers by this author , Junjie YangJunjie Yang Birmingham, AL Search for more papers by this author , qinkun zhangqinkun zhang Univ of Alabama at Birmingham, Birmingham, AL Search for more papers by this author , Hind LalHind Lal UAB, Birmingham, AL Search for more papers by this author , Jianyi ZhangJianyi Zhang UNIVERSITY OF ALABAMA AT BIRMINGHAM, Birmingham, AL Search for more papers by this author and Gangjian QinGangjian Qin Univ of Alabama at Birmingham, Birmingham, AL Search for more papers by this author Originally published8 Nov 2021https://doi.org/10.1161/circ.144.suppl_1.11334Circulation. 2021;144:A11334AbstractBackground & Hypothesis: Following acute myocardial infarction (AMI), cardiac exosomes are released into circulation (PBExo), thereby transferring cargo miRNAs (miRs) to remote organs to trigger systemic responses. However, the scope and impact of cardiac miR transfer is largely unknown. Since T. gondii uracil phosphoribosyltransferase (UPRT) can convert 4-thiouracil into 4-thiouridine (4TU), then incorporating into nascent RNAs, and the 4TU-labeled RNAs can be identified by thio-linked-biotinylation and streptavidin-affinity isolation, we hypothesize that cardiomyocyte (CM)-specific expression of UPRT (CMUPRT) allows labeling and tracking of CM-derived miRs in PBExo and peripheral organs.Methods & Results: We generated CMUPRT mice by crossing αMHC-Cre and CA-GFPstopflox-UPRT mice. Six hours after 4-thiouracil injection, RNAs were isolated from the heart and PBExo and found to be labeled with high specificity and sensitivity. Then we attempted to isolate representative miRs of different tissue specificities from PBExo and multiple organs; only CM specific miR-208a, but not other-tissue specific miRs, was 4TU labeled, thus isolated, abundantly in PBExo and lung. Among FACS-sorted lung cells, endothelial cells (ECs) have the highest CMmiR-208a level. Next, we monitored CMmiR-208a levels after AMI, which peaked in PBExo at 12 h and in the lung at 24 h. Since miR-208a is from the intron 29 of the cardiac α-MHC, we measured α-MHC transcript in the lung, which was barely detectable. To determine the biological effect of PBExo-mediated CMmiR-208a transfer, we i.v. injected PBExo obtained from Sham and AMI mice to intact mice; Sham-Exo and to a greater extent, AMI-Exo, but not Exo from LNA-anti-miR-208a pre-treated mice, downregulated the protein expression of miR-208a target genes (Glyr1, Tmbim6, and NLK) in the lung. Since all the three proteins suppress key effectors in the NF-kB pathway, we examined NF-kB’s classic targets (ICAM-1, VCAM-1 and E-selectin); PBExo-mediated Glyr1, Tmbim6, and NLK downregulation was associated with ICAM-1, VCAM-1 and E-selectin upregulation.Conclusion:CMUPRT expression permits labeling and tracking of CMmiRs in PBExo and organs; cardiac Exo and CMmiR-208a may contribute to AMI-associated lung inflammation.FootnotesAuthor Disclosures: For author disclosure information, please visit the AHA Scientific Sessions 2021 Online Program Planner and search for the abstract title. eLetters(0) eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate. Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page. Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetails November 16, 2021Vol 144, Issue Suppl_1 Advertisement Article Information Metrics © 2021 by American Heart Association, Inc.https://doi.org/10.1161/circ.144.suppl_1.11334 Originally publishedNovember 8, 2021 KeywordsMyocardial infarctionMicroRNAGene transferPulmonaryEndothelial Advertisement