Vasoinhibins are not the only members of the PRL GHPL family that inhibit angiogenesis.SD PRL, a molecular mimic of naturally occurring phosphorylated PRL, was recently shown to inhibit Ticagrelor angiogenesis by interfering with endothelial cell migration, proliferation, survival, and growth factor signaling. Systemic ANG II is primarily produced within the pulmonary circulation, and its formation is limited by the availability of circulating renin released by the juxtaglomerular cells of the kidney.ANG I can be further processed to angiogenic angiotensin II, each of which can be cleaved to yield peptides with no described effects on angiogenesis.The singleletter amino acid composition of each smaller peptide is indicated.Increasing evidence indicates that members of RAS exert both positive and negative effects on angiogenesis.Because the main role of RAS is to maintain body uid homeostasis in response to a drop in perfusion pressure, RAS hormones likely participate in controlling neovascularization during vasoconstrictionassociated ischemia.Intricate mechanisms govern their contrasting actions on angiogenesis and involve the activation of different receptor subtypes with opposite outcomes depending on specic tissue and disease conditions as well as the proteolytic conversion of larger precursor molecules, which may or may not have angiogenic actions, into smaller angiogenic or antiangiogenic peptides.ANG II stimulates vessel proliferation in the chick embryo chorioallantoic membrane. The two G proteincoupled receptors for ANG II, AT and AT, have been identied in endothelial cells, and AT is the main mediator of the proangiogenic actions of ANG II.Likewise, inhibitors of AT, but not of AT, prevent the stimulatory effects of ANG II on the proliferation and tube formation of cultured endothelial cells. However, in kidney, both AT and AT inhibitors are effective, PDGF, and TGF. On the other hand, ANG II is antiangiogenic under certain conditions, as inhibition of Balsalazide endogenous ANG II production or action by treatment with ACE inhibitors or AT and AT blockers, respectively, stimulates angiogenesis in vivo. ANG II may inhibit angiogenesis by activating the AT receptor.However, the contribution of each receptor subtype to the antiangiogenic effect of ANG II appears to depend on the chosen angiogenesis model.Although much needs to be learned about the mechanisms controlling the dual effects on angiogenesis of AT and AT, it is generally accepted that the two receptors essentially mediate contrasting effects of ANG II. AT receptors are ubiquitously expressed and responsible for most of the wellknown actions of ANG II, including vasoconstriction, aldosterone and vasopressin release, renal sodium and water reabsorption, sympathetic activation, augmented cardiac contractility, smooth muscle cell proliferation, vascular and cardiac hypertrophy, inammation, and oxidative stress.In contrast, AT receptors are restricted to organs like the brain, kidney, adrenals, uterus, ovary, and the cardiovascular system, where their activation leads to vasodilation, lower blood pressure, reduced cardiac and vascular hypertrophy, antiinammation, and suppressed growth, tissue repair, and apoptosis.Each receptor subtype activates multiple signaling pathways, and the opposing inuence of the two receptor subtypes is supported by signaling experiments in vitro.For example, AT receptors upregulate the expression of VEGF and angiopoietin in microvascular endothelial cells by stimulating the release of heparinbinding EGF followed by the transactivation of the EGF receptor, whereas AT attenuates these actions by blocking EGF receptor phosphorylation.