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

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 CM-derived exosomal miR-29a is involved in regulating cardiac microvascular endothelial cell (CMEC) homeostasis during the development of myocardial hypertrophy has not clearly determined. Methods: Angiotensin II (Ang II) was used to induce CM hypertrophy, and ultracentrifugation was then used to extract exosomes from CM-conditioned medium. CMECs were cocultured with 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 expression of miR-29a 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 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.

The potential roles of exosomes in pathological cardiomyocyte hypertrophy mechanisms and therapy: A review

“…[90] This alteration impacts critical endothelial cell processes, including proliferation, migration, and tube formation. [90] As a result, exosomes play a pivotal role as mediators in the angiogenic response within the cardiac microenvironment, exerting a substantial influence on the processes of cardiac hypertrophy and remodeling. [90] 4.…”

“…[90] As a result, exosomes play a pivotal role as mediators in the angiogenic response within the cardiac microenvironment, exerting a substantial influence on the processes of cardiac hypertrophy and remodeling. [90] 4. Exosomes and signaling pathways in pathological cardiac hypertrophy Pathological cardiac hypertrophy involves complex signaling pathways influenced by exosomes, which are integral to the communication between cardiomyocytes and other cardiac cells.…”

“…[88,89] Recent studies reveal that exosomal MiR-29a, released from cardiomyocytes, engages in direct interaction with cardiac microvascular endothelial cells. [90] This interaction involves MiR-29a molecules targeting and subsequently downregulating VEGFA expression in endothelial cells, thereby significantly altering their functional properties. [90] This alteration impacts critical endothelial cell processes, including proliferation, migration, and tube formation.…”

“…[90] This interaction involves MiR-29a molecules targeting and subsequently downregulating VEGFA expression in endothelial cells, thereby significantly altering their functional properties. [90] This alteration impacts critical endothelial cell processes, including proliferation, migration, and tube formation. [90] As a result, exosomes play a pivotal role as mediators in the angiogenic response within the cardiac microenvironment, exerting a substantial influence on the processes of cardiac hypertrophy and remodeling.…”

“…[90] As a result, exosomes play a pivotal role as mediators in the angiogenic response within the cardiac microenvironment, exerting a substantial influence on the processes of cardiac hypertrophy and remodeling. [90]…”