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. 2022 Oct 2;11(19):3108. doi: 10.3390/cells11193108

Figure 2.

Figure 2

Postulated mechanisms through which PC-EVs are involved in angiogenesis. In response to PDGF-BB, PC-EVs containing several growth factors (CTGF, PLGF, FGF, VEGF) are released. These are transferred to the recipient endothelial cells (ECs) to induce pro-angiogenic signaling in the ECs and promote angiogenesis. CTGF activates the ERK1/2-STAT3 axis in vascular endothelial cells and facilitates the onset of the initial stage of angiogenesis. VEGF and FGF released by platelet-derived EVs act on the VEGF and FGF receptors to exert a pro-angiogenic effect by activating PI3 kinase, src kinase, and ERK1/2. The cargo of EVs also has various miRNAs. Among these, miR26a targets PTEN, activating PI3K/AKT to promote survival and proliferation in the ECs and, thus, angiogenesis. Under hypoxic conditions, PC-released EVs contain circular RNA. Among the circRNAs, circEhmt1 enhances the expression of the transcription factor NFIA while inhibiting the NRLP3 inflammasome, thereby promoting survival and proliferation of the ECs and promoting angiogenesis. The black arrow indicates identified components and mechanism of action of PC-EVs, and the magenta arrow indicates hypothesized Mechanism in PC-EVs based on identified mechanisms from other EVs. (miRNA: an acronym for micro RNA; circRNA: circular RNA; EVs: extracellular vesicles; VEGF: Vascular endothelial growth factor; PLGF: placental growth factor; CTGF: connective tissue growth factor; ERK1/2: extracellular signal-regulated kinase 1 and 2; PI3K: phosphoinositide 3-kinase; PTEN: phosphatase and TENsin homolog deleted on chromosome 10; STAT-3: Signal transducer and activator of transcription).