Exosomes participate in many mechanisms that promote hepatic tumour angiogenesis. Existing literature has indicated that the lncRNA H19, released via exosomes from CD90 + liver cancer cells, increases the expression of VEGF and the production of VEGF-R1, hence enhancing angiogenesis [
123]. A large body of evidence has documented that exosomal microRNA-32-5p increases angiogenesis by activating the PTEN/PI3K/Akt pathway [
124]. Moreover, miR-210 transferred by exosomes enhanced angiogenesis by directly repressing the expression of SNAD4 and STAT6 [
125]. A series of experiments have been performed to show that miR-155 mediates angiogenic activity via exosomes under hypoxia and that it may be associated with proangiogenic factors [
126]. Hepatocellular carcinoma (HCC) cell-derived exosomal miRNA-21 directly targeted PTEN (gene of phosphate and tension homology deleted on chromosome ten), leading to the activation of PDK1/AKT signalling in Hepatic stellate cells (HSCs), which are then transformed into CAFs [
127]. Activated CAFs further promote cancer angiogenesis by secreting angiogenic cytokines, including VEGF, MMP2, MMP9, bFGF and TGF-β [
128]. Furthmore, miR-21 can also shape a vascular microenvironment for HCC via the STAT3/VEGF signalling pathway, and miR-221 can activate the SAND/NF-κB pathway to upregulate the expression of CXCL16, which is an angiogenic factor [
129]. Lysyl oxidase-like 1–4 (LOXL1–4), which was secreted by HCC-derived exosomes in a paracrine mechanism, was also reported to promote angiogenesis [
130]. Exosomal circRNA-100,338 was found to be upregulated and could increase angiogenesis of HCC cells [
131]. Moreover, circRNA-100,338 might decrease the expression of VE-cadherin and ZO-1 in HUEVCs to promote vascular endothelial cell permeability [
131]. A pro‑angiogenic role has also been demonstrated for angiopoietin-2 (ANGPT2), which has been found to be contained in exosomes secreted by HCC cells and activates the Tie2-independent, AKT/eNOS and AKT/β-catenin pathways. [
132] Research has shown that HCC cell-derived exosomes carrying LINC00161 activate the ROCK2 signalling pathway by inhibiting miR-590-3p and strengthen the tube-forming ability of HUVECs [
133]. Hiroshi Yukawa et al. verified that HepG2-exosomes activated lumen formation by HUVECs [
134]. Exosomes contain both upregulated and downregulated miRNAs, but their detailed influence is unknown [
134]. Shihua Wang et al. found that HCC cell HepG2-derived exosomes could activate various kinases, such as AKT, STAT5α, GSK3 alpha/beta, p38 alpha, and ERK1/2, as well as the NF-κB signalling pathway in adipocytes to promote tube formation [
135]. Recent experimental evidence has highlighted the role of exosomal microRNA-378b in HCC. HepG2 cell-derived exosomal miR-378b enhanced HCC cell angiogenesis by increasing MMP9, FGF2 and VEGFA expression, which may be linked with TGFBR3 [
136]. Exosomal miR-1290 enhanced tube formation by directly targeting SMEK1 to alleviate the suppression of VEGFR2 phosphorylation [
137]. In addition, HCC-cell-derived exosomes can be used as carriers to deliver CircCMTM3 to HUVECs. CircCMTM3 regulates SOX9 expression in HUVECs by sponging miR‐3619‐5p, which promotes angiogenesis and HCC cell tumorigenesis [
138]. Moreover, exosome-delivered small nucleolar RNA host gene 16 (SNHG16) regulates GALNT1 expression by sponging miR-4500 via the PI3K/Akt/mTOR pathway to activate the formation of new HCC blood vessels, thus promoting the progression of HCC [
139]. Exosomal RAB13, a potential regulator of HCC metastasis, was also associated with VEGF levels, microvessel density, and tube formation by vascular endothelial cells in both in vitro and in vivo models, suggesting that it promotes angiogenesis [
140]. Moreover, HCC cell-derived exosomes containing C-Type Lectin Domain Family 3 Member B (CLEC3B) were able to inhibit the angiogenic ability of HMVECs via the repression of VEGF by activating AMPK signalling [
141]. By targeting the transcription factor ERG (erythroblast transformation‑specific (ETS)‑related gene), exosomal miR-200b-3p plays a negative role in angiogenesis [
142]. Similarly, exosomal miR-3682-3p targeted angiopoietin-1 (ANGPT1) via RAS-MEK1/2-ERK1/2 signalling, and attenuated angiogenesis [
143]. All of these findings may indicate potential therapeutic targets for antiangiogenic therapy.