Vascular endothelial growth factor-A regulation of blood vessel sprouting in health and disease

Abstract

Introduction Vascular endothelial growth factors (VEGFs) comprise of a multigene-encoded family of cytokines that display remarkable effects in different tissues including the vascular, epithelial and neuronal tissues. Such factors bind to both membrane-bound and soluble receptor isoforms that regulate the ability of these cytokines to trigger profound biochemical changes within cells, resulting in changes to metabolism, gene expression, cell proliferation, apoptosis and homeostasis. The cornerstone of this biochemical control is based on the interaction between soluble factors such as VEGFs and membrane-bound receptors such as VEGF receptor tyrosine kinases (VEGFRs). The endothelial monolayer that lines all blood vessels responds to VEGFs to regulate many aspects of vascular physiology. Dysfunction in the VEGF-A signalling pathways is implicated in a wide variety of diseases ranging from solid tumour metastasis to atherosclerosis. VEGF binding to membrane VEGFRs triggers intracellular signalling, post-translational protein modifications , trafficking and proteolysis. Temporal and spatial coordination of such events is critical for programming downstream responses by the endothelium. In this review, we have discussed the biochemical mechanisms that underlie new blood vessel sprouting mediated by VEGF-like cytokines. Conclusion The development of primary cell systems, multicellular models, organ culture and animal models, will dramatically increase our ability to understand the biochemical basis for how this important class of cytokines regulate animal physiology. Targeting such pathways directly or indirectly using humanised antibodies or small molecule inhibitors, is important for treating a wide variety of pathological states including solid tumour growth and metastasis, age-related macular degeneration and conditions involving blood vessel repair and regeneration.

Extra Virgin Olive Oil Modulates Vasodilator Enzyme Level by Repairing Angiogenesis Function in Rat Model of Preeclampsia

“…CCP will produce eNOS. Shb molecule adapter binds to Tyr1175,which activates PI3K,and then AKT produces eNOS and gives rise to vascular permeability, cell migration, and cell survival (8). In preeclampsia condition, the process above is hampered due to high Sflt-1 and low VEGF, so the process of forming eNOS is interrupted.…”

“…CCP will produce eNOS. The adapter Shb molecule binds to Tyr1175 that activates PI3K, then AKT produces eNOS and gives rise to vascular permeability, cell migration, and cell survival (8). In the condition of preeclampsia, the above process is hampered due to the high sFlt-1 so that the process of eNOS formation is disrupted, Nitric Oxide (NO) decreases, and blood pressure increases.…”

“…The vascular endothelial repair will reduce sFlt-1 level; thus, the bond between Flt1 and VEGF increases. In turn, the bond between Flt1 and VEGF will increase eNOS production through PLC-gamma and PI3K lines (8). Besides, the polyphenols contained in EVOO modulate the activation of the transcription factor of Nuclear Factor (Erythroid-Derived 2)-Like 2 (Nrf2) that plays a role in the regulation of angiogenic, resulting in an increase in VEGF level (9).…”

Ethanolic Extract of Nerium indicum Mill. Decreases Transforming Growth Factor Beta-1 and Vascular Endothelial Growth Factor Expressions in Keloid Fibroblasts

“…In keloid tumors, there is an increased VEGF expression that binds to the VEGFR receptor, activating signaling pathways for angiogenesis and neovascularization of tyrosine kinase. Activation of VEGFR by VEGF-A causes autophosphorylation of tyrosine residues at the VEGFR receptors, thereby activating mitogen-activated protein-kinase (MAP-K) which causes cell proliferation and migration as well as activation of AKT/ERK proteins producing eNOS so that vascular permeability increases [22]. Fibrosis in keloid tissue is caused by increased VEGF-A phosphorylation with its receptors.…”

Cell-Based Treatment of Ischemic Heart Disease: Rationale for the Use of VEGF-Eluting Adult Progenitor Cells

“…The maintenance and production of vessels rely on several growth factors and cytokines; VEGF is one of the most critical and well-studied angiogenic growth factors [11]. VEGF is involved in several angiogenic functions, to include endothelial cell migration, mitogenesis, vascular sprouting, and vascular tube formation [12,13]. Several isoforms of VEGF are endogenously active; VEGF factor A (VEGF-A) is the most active isoform and is essential for mammalian development and function [14,15].…”