The role of miR-126 in embryonic angiogenesis, adult vascular homeostasis, and vascular repair and its alterations in atherosclerotic disease

A comparison of microRNA expression profiles from splenic hemangiosarcoma, splenic nodular hyperplasia, and normal spleens of dogs

“…Additional work has shown that mir-126 levels are increased in endothelial precursor cells, which are the cells of origin of hemangiosarcoma, explaining their upregulation in this particular tumor type [12, 40–43]. Mir-126 can behave in both pro- and anti-angiogenic ways, but is pro-angiogenic in endothelial precursor cells and actively proliferating and migrating endothelial cells [41]. Mir-126 enhances angiogenesis by increasing VEGF expression through its targeting of the PI3K regulatory subunit 2 (p85β) [39, 40, 43, 49].…”

“…Mir-126 may be acting in concert with other mediators to influence this pathway, leading to increased VEGF production and a pro-survival state. Mir-126 also targets regulator of G-protein signaling (RGS16) which inhibits CXCR4, an important protein in angiogenesis [41, 51]. When CXCR4 is activated, both circulating hematopoietic stem cells and prostate cancer cells have increased endothelial cell adhesion and transendothelial migration, indicating this pathway may direct metastasis [52, 53].…”

Obesity Downregulates MicroRNA‐126 Inducing Capillary Rarefaction in Skeletal Muscle: Effects of Aerobic Exercise Training

“…Expression of miR126 is enriched in endothelial cells and endothelial progenitor cells. This miRNA is involved in the induction of signaling of the embryonic vasculogenesis, being related to a differentiation of embryonic stem cells in endothelial cells and endothelial progenitor cells, promoting their maturation [22]. Knockdown of miR-126 expression in animals results in an impairment in the formation and maintenance of blood vessels and partial embryonic lethality [7].…”

Epigenetic Programming of Cardiovascular Disease by Perinatal Hypoxia and Fetal Growth Restriction

“…Considering that the effect of endothelial-specific transcription factors such as KLF2 and HoxA9 does not explain the protein expression levels present in this cell type [65], an "endothelial epigenetic code" regulating the expression of crucial genes has been suggested [52,66]. Growing evidence shows that DNA methylation, histone PTM, and miRNAs [67] play an important role in the embryonic origins of endothelial cells (EC), as well as their homeostasis during life. The epigenetic regulation of NOS3 gene has been extensively studied in EC and non-EC, showing that ECs have a distinctive pattern of DNA methylation and histone PTMs [65].…”

“…It has been proposed that miR-126 is an endothelial-specific miRNA which promotes angiogenic activation in progenitor cells during early development, as well as vascular repair in adult subjects, while in mature endothelial cells, it has an anti-atherogenic effect maintaining endothelial quiescence and preventing inflammation [67]. In ob/ob mice, antioxidant treatment induces a miR-126-dependent anti-inflammatory and antioxidant vascular response [98], an effect also observed in HUVEC [99].…”