Heart-targeting exosomes from human cardiosphere-derived cells improve the therapeutic effect on cardiac hypertrophy

Autor:	Liang Mao, Yun-Da Li, Ruo-Lan Chen, Gang Li, Xiao-Xia Zhou, Fei Song, Chan Wu, Yu Hu, Yi-Xiang Hong, Xitong Dang, Gui-Rong Li, Yan Wang
Rok vydání:	2022
Předmět:	Angiotensin II Biomedical Engineering Pharmaceutical Science Medicine (miscellaneous) Lysosome-Associated Membrane Glycoproteins Bioengineering Cardiomegaly Exosomes Applied Microbiology and Biotechnology Rats Mice MicroRNAs Cytokine Receptor gp130 Molecular Medicine Animals Humans Myocytes Cardiac Peptides Proto-Oncogene Proteins c-akt
Zdroj:	Journal of nanobiotechnology. 20(1)
ISSN:	1477-3155
Popis:	Exosomes of human cardiosphere-derived cells (CDCs) are very promising for treating cardiovascular disorders. However, the current challenge is inconvenient delivery methods of exosomes for clinical application. The present study aims to explore the potential to enhance the therapeutic effect of exosome (EXO) from human CDCs to myocardial hypertrophy. A heart homing peptide (HHP) was displayed on the surface of exosomes derived from CDCs that were forced to express the HHP fused on the N-terminus of the lysosomal-associated membrane protein 2b (LAMP2b). The cardiomyocyte-targeting capability of exosomes were analyzed and their therapeutic effects were evaluated in a mouse model of myocardial hypertrophy induced by transverse aorta constriction (TAC). The molecular mechanisms of the therapeutic effects were dissected in angiotensin II-induced neonatal rat cardiomyocyte (NRCMs) hypertrophy model using a combination of biochemistry, immunohistochemistry and molecular biology techniques. We found that HHP-exosomes (HHP-EXO) accumulated more in mouse hearts after intravenous delivery and in cultured NRCMs than control exosomes (CON-EXO). Cardiac function of TAC mice was significantly improved with intravenous HHP-EXO administration. Left ventricular hypertrophy was reduced more by HHP-EXO than CON-EXO via inhibition of β-MHC, BNP, GP130, p-STAT3, p-ERK1/2, and p-AKT. Similar results were obtained in angiotensin II-induced hypertrophy of NRCMs, in which the beneficial effects of HHP-EXO were abolished by miRNA-148a inhibition. Our results indicate that HHP-EXO preferentially target the heart and improve the therapeutic effect of CDCs-exosomes on cardiac hypertrophy. The beneficial therapeutic effect is most likely attributed to miRNA-148a-mediated suppression of GP130, which in turn inhibits STAT3/ERK1/2/AKT signaling pathway, leading to improved cardiac function and remodeling.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::56bba9c14f24def8415ebb686a54880f https://pubmed.ncbi.nlm.nih.gov/36195937 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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