AngiomiRs: Potential Biomarkers of Pregnancy’s Vascular Pathologies

Figure 1

Some of the main roles of angiomiRs in placentation. Panel (a) shows key moments after blastocyst adherence to endometrial epithelium. On day 9, the trophoblast starts endometrium invasion which lasts until day 14 when primary villi start to form. Panel (b) represents cytotrophoblast invasion (migration and proliferation), which is responsible for increasing vascular capacity, showing how poor migration can decrease vessel transformation and induce increased blood pressure and decreased blood flow. Panel (c) shows some placental angiomiRs reported in PE, IUGR, and/or GD: Number 1 shows that before implantation 17β HSD 1 enzyme transforms estrone to estradiol in the corpus luteum, inducing apical endometrial epithelial differentiation for blastocyst accession. 17β HSD 1 is a validated target of miR-210 and miR-518c. Number 2 shows miR-210 regulation on EFNA3, the latter being expressed on trophoectodermal cells close to the inner cell mass of the blastocyst, guiding its location. In 1 and 2, it is possible to elucidate the potential problems that overexpression of miR-210 could cause, with evidence in PE. Number 3 shows miR-328 regulation on hyaluronate receptor CD44, which is involved in the cytotrophoblast and endothelial cells migration, in maternal vessels, in response to the OPN protein gradient’s attraction, released from endometrial gland. Number 4 shows miR-126 and miR-21 regulation on VEGF species, the vascular endothelial growth factor implicated in angiogenesis promotion, as well as miR-16 and miR-29b on VEGFA. Number 5 shows miR-222 and miR-221 regulating c-Kit; overexpression of these miRNAs produces an imbalance with its ligand SCF, with consequences on proliferative signal. Number 6 shows miR-155 downregulating eNOS, with possible damage on vasodilation and permeability; cyclin D1 (number 7) is a target of the same miR-155, generating problems on proliferation. Number 8 shows cluster miR-17-92 regulation on TGFβ, a key growth factor involved in cytotrophoblast proliferation and differentiation.