Sacubitril/Valsartan Improves Cardiac Function and Decreases Myocardial Fibrosis Via Downregulation of Exosomal miR-181a in a Rodent Chronic Myocardial Infarction Model.

Journal of the American Heart Association
Evgeniya VaskovaPhillip C Yang

Abstract

Background Exosomes are small extracellular vesicles that function as intercellular messengers and effectors. Exosomal cargo contains regulatory small molecules, including miRNAs, mRNAs, lncRNAs, and small peptides that can be modulated by different pathological stimuli to the cells. One of the main mechanisms of action of drug therapy may be the altered production and/or content of the exosomes. Methods and Results We studied the effects on exosome production and content by neprilysin inhibitor/angiotensin receptor blockers, sacubitril/valsartan and valsartan alone, using human-induced pluripotent stem cell-derived cardiomyocytes under normoxic and hypoxic injury model in vitro, and assessed for physiologic correlation using an ischemic myocardial injury rodent model in vivo. We demonstrated that the treatment with sacubitril/valsartan and valsartan alone resulted in the increased production of exosomes by induced pluripotent stem cell-derived cardiomyocytes in vitro in both conditions as well as in the rat plasma in vivo. Next-generation sequencing of these exosomes exhibited downregulation of the expression of rno-miR-181a in the sacubitril/valsartan treatment group. In vivo studies employing chronic rodent myocardial injury...Continue Reading

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Citations

Feb 2, 2021·Frontiers in Pharmacology·Wenchao ZhangYi-Fei Dong
Mar 23, 2021·Frontiers in Cardiovascular Medicine·Wei Wang, Hao Zheng
Jun 3, 2021·International Journal of Molecular Sciences·Mihir Parikh, Grant N Pierce
Aug 28, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Pema RajShelley Zieroth

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Methods Mentioned

BETA
flow cytometry
Reverse Transcription Polymerase
RNA Assay
chips

Software Mentioned

Nanosight
PRINSEQ
FastQC
FlowJo
Bowtie
DESeq
FastqMcf
Image J

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