Title:Exosomal MiR-29a in Cardiomyocytes Induced by Angiotensin II Regulates
Cardiac Microvascular Endothelial Cell Proliferation, Migration and
Angiogenesis by Targeting VEGFA
Volume: 22
Issue: 4
关键词:
心肌细胞肥大，心肌细胞，心脏微血管内皮细胞，外泌体，miR-29a, VEGFA。
摘要:
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.
