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Research Article

Exosomal MiR-29a in Cardiomyocytes Induced by Angiotensin II Regulates Cardiac Microvascular Endothelial Cell Proliferation, Migration and Angiogenesis by Targeting VEGFA

Author(s): Guangzhao Li, Zhimei Qiu, Chaofu Li, Ranzun Zhao, Yu Zhang, Changyin Shen, Weiwei Liu, Xianping Long, Shaowei Zhuang, Yan Wang* and Bei Shi*

Volume 22, Issue 4, 2022

Published on: 01 April, 2022

Page: [331 - 341] Pages: 11

DOI: 10.2174/1566523222666220303102951

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Abstract

Background: Exosomes released from cardiomyocytes (CMs) potentially play an important role in angiogenesis through microRNA (miR) delivery. Studies have reported an important role for miR-29a in regulating angiogenesis and pathological myocardial hypertrophy. However, whether CMderived exosomal miR-29a is involved in regulating cardiac microvascular endothelial cell (CMEC) homeostasis during myocardial hypertrophy has not been determined.

Methods: Angiotensin II (Ang II) was used to induce CM hypertrophy, and ultracentrifugation was then used to extract exosomes from a CM-conditioned medium. CMECs were cocultured with a conditioned medium in the presence or absence of exosomes derived from CMs (Nor-exos) or exosomes derived from angiotensin II-induced CMs (Ang II-exos). Moreover, a rescue experiment was performed using CMs or CMECs infected with miR-29a mimics or inhibitors. Tube formation assays, Transwell assays, and 5-ethynyl-20-deoxyuridine (EdU) assays were then performed to determine the changes in CMECs treated with exosomes. The miR-29a expression was measured by qRT-PCR, and Western blotting and flow cytometry assays were performed to evaluate the proliferation of CMECs.

Results: The results showed that Ang II-induced exosomal miR-29a inhibited the angiogenic ability, migratory function, and proliferation of CMECs. Subsequently, the downstream target gene of miR- 29a, namely, vascular endothelial growth factor (VEGFA), was detected by qRT-PCR and Western blotting, and the results verified that miR-29a targeted the inhibition of the VEGFA expression to subsequently inhibit the angiogenic ability of CMECs.

Conclusion: Our results suggest that exosomes derived from Ang II-induced CMs are involved in regulating CMCE proliferation, migration, and angiogenesis by targeting VEGFA through the transfer of miR-29a to CMECs.

Keywords: Cardiomyocyte hypertrophy, cardiomyocyte, cardiac microvascular endothelial cell, exosome, miR-29a, VEGFA.

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