Peptide Hormone Regulation of Angiogenesis

2009 ◽  
Vol 89 (4) ◽  
pp. 1177-1215 ◽  
Author(s):  
Carmen Clapp ◽  
Stéphanie Thebault ◽  
Michael C. Jeziorski ◽  
Gonzalo Martínez De La Escalera
Keyword(s):  
Endothelial Cells ◽  
Peptide Hormone ◽  
Specific Protein ◽  
Placental Lactogen ◽  
Hormone Regulation ◽  
Protein Cleavage ◽  
Vessel Growth ◽  
Health And Disease ◽  
Opposing Effects ◽  
Endothelial Growth Factor

It is now apparent that regulation of blood vessel growth contributes to the classical actions of hormones on development, growth, and reproduction. Endothelial cells are ideally positioned to respond to hormones, which act in concert with locally produced chemical mediators to regulate their growth, motility, function, and survival. Hormones affect angiogenesis either directly through actions on endothelial cells or indirectly by regulating proangiogenic factors like vascular endothelial growth factor. Importantly, the local microenvironment of endothelial cells can determine the outcome of hormone action on angiogenesis. Members of the growth hormone/prolactin/placental lactogen, the renin-angiotensin, and the kallikrein-kinin systems that exert stimulatory effects on angiogenesis can acquire antiangiogenic properties after undergoing proteolytic cleavage. In view of the opposing effects of hormonal fragments and precursor molecules, the regulation of the proteases responsible for specific protein cleavage represents an efficient mechanism for balancing angiogenesis. This review presents an overview of the actions on angiogenesis of the above-mentioned peptide hormonal families and addresses how specific proteolysis alters the final outcome of these actions in the context of health and disease.

scholarly journals Small interfering RNA-induced TLR3 activation inhibits blood and lymphatic vessel growth

2009 ◽  
Vol 106 (17) ◽  
pp. 7137-7142 ◽  
Author(s):  
Won Gil Cho ◽  
Romulo J. C. Albuquerque ◽  
Mark E. Kleinman ◽  
Valeria Tarallo ◽  
Adelaide Greco ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Mouse Models ◽  
Tissue Injury ◽  
Vascular Endothelial ◽  
Small Interfering Rnas ◽  
Vessel Growth ◽  
Interfering Rna ◽  
Endothelial Growth Factor ◽  
Tlr3 Activation

Neovascularization in response to tissue injury consists of the dual invasion of blood (hemangiogenesis) and lymphatic (lymphangiogenesis) vessels. We reported recently that 21-nt or longer small interfering RNAs (siRNAs) can suppress hemangiogenesis in mouse models of choroidal neovascularization and dermal wound healing independently of RNA interference by directly activating Toll-like receptor 3 (TLR3), a double-stranded RNA immune receptor, on the cell surface of blood endothelial cells. Here, we show that a 21-nt nontargeted siRNA suppresses both hemangiogenesis and lymphangiogenesis in mouse models of neovascularization induced by corneal sutures or hindlimb ischemia as efficiently as a 21-nt siRNA targeting vascular endothelial growth factor-A. In contrast, a 7-nt nontargeted siRNA, which is too short to activate TLR3, does not block hemangiogenesis or lymphangiogenesis in these models. Exposure to 21-nt siRNA, which we demonstrate is not internalized unless cell-permeating moieties are used, triggers phosphorylation of cell surface TLR3 on lymphatic endothelial cells and induces apoptosis. These findings introduce TLR3 activation as a method of jointly suppressing blood and lymphatic neovascularization and simultaneously raise new concerns about the undesirable effects of siRNAs on both circulatory systems.

scholarly journals Roles of prolactin and related members of the prolactin/growth hormone/placental lactogen family in angiogenesis

2002 ◽  
Vol 173 (2) ◽  
pp. 219-238 ◽  
Author(s):  
AM Corbacho ◽  
G Martinez De La Escalera ◽  
C Clapp
Keyword(s):  
Growth Hormone ◽  
Blood Vessels ◽  
Biological Activities ◽  
Specific Protein ◽  
Proteolytic Processing ◽  
Placental Lactogen ◽  
Protease Production ◽  
Endothelial Cell Proliferation ◽  
Related Protein ◽  
Protein Cleavage

Prolactin, growth hormone and placental lactogen are members of a family of polypeptide hormones which share structural similarities and biological activities. Numerous functions have been attributed to these hormones, among which stand out their recently discovered effects on angiogenesis, the process by which new blood vessels are formed from the pre-existing microvasculature. Prolactin, growth hormone and placental lactogen, along with two non-classical members of the family, proliferin and proliferin-related protein, can act both as circulating hormones and as paracrine/autocrine factors to either stimulate or inhibit various stages of the formation and remodeling of new blood vessels, including endothelial cell proliferation, migration, protease production and apoptosis. Such opposing actions can reside in similar but independent molecules, as is the case of proliferin and proliferin-related protein, which stimulate and inhibit angiogenesis respectively. The potential to exert opposing effects on angiogenesis can also reside within the same molecule as the parent protein can promote angiogenesis (i.e. prolactin, growth hormone and placental lactogen), but after proteolytic processing the resulting peptide fragment acquires anti-angiogenic properties (i.e. 16 kDa prolactin, 16 kDa growth hormone and 16 kDa placental lactogen). The unique properties of the peptide fragments versus the full-length molecules, the regulation of the protease responsible for specific protein cleavage, the selective expression of specific receptors and their associated signal transduction pathways are issues that are being investigated to further establish the precise contribution of these hormones to angiogenesis under both physiological and pathological situations. In this review article, we summarize the known and speculative issues underlying the effects of the prolactin, growth hormone and placental lactogen family of proteins on angiogenesis, and address important remaining enigmas in this field of research.

scholarly journals Sub-Toxic Human Amylin Fragment Concentrations Promote the Survival and Proliferation of SH-SY5Y Cells via the Release of VEGF and HspB5 from Endothelial RBE4 Cells

2018 ◽  
Vol 19 (11) ◽  
pp. 3659 ◽  
Author(s):  
Giuseppe Caruso ◽  
Claudia Fresta ◽  
Giacomo Lazzarino ◽  
Donatella Distefano ◽  
Paolo Parlascino ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Peptide Hormone ◽  
Vegf Receptor ◽  
Protective Effects ◽  
Amyloid Deposits ◽  
Toxic Concentration ◽  
A Cell ◽  
Human Amylin ◽  
Toxic Concentrations ◽  
Endothelial Growth Factor

Human amylin is a 37-residue peptide hormone (hA1-37) secreted by β-cells of the pancreas and, along with insulin, is directly associated with type 2 diabetes mellitus (T2DM). Amyloid deposits within the islets of the pancreas represent a hallmark of T2DM. Additionally, amylin aggregates have been found in blood vessels and/or brain of patients with Alzheimer’s disease, alone or co-deposited with β-amyloid. The purpose of this study was to investigate the neuroprotective potential of human amylin in the context of endothelial-neuronal “cross-talk”. We initially performed dose-response experiments to examine cellular toxicity (quantified by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] MTT assay) of different hA17–29 concentrations in endothelial cells (RBE4). In the culture medium of these cells, we also measured heat shock protein B5 (HspB5) levels by ELISA, finding that even a sub-toxic concentration of hA17–29 (3 µM) produced an increase of HspB5. Using a cell medium of untreated and RBE4 challenged for 48 h with a sub-toxic concentration of hA17–29, we determined the potential beneficial effect of their addition to the medium of neuroblastoma SH-SY5Y cells. These cells were subsequently incubated for 48 h with a toxic concentration of hA17–29 (20 µM). We found a complete inhibition of hA17–29 toxicity, potentially related to the presence in the conditioned medium not only of HspB5, but also of vascular endothelial growth factor (VEGF). Pre-treating SH-SY5Y cells with the anti-Flk1 antibody, blocking the VEGF receptor 2 (VEGFR2), significantly decreased the protective effects of the conditioned RBE4 medium. These data, obtained by indirectly measuring VEGF activity, were strongly corroborated by the direct measurement of VEGF levels in conditioned RBE4 media as detected by ELISA. Altogether, these findings highlighted a novel role of sub-toxic concentrations of human amylin in promoting the secretion of proteic factors by endothelial cells (HspB5 and VEGF) that support the survival and proliferation of neuron-like cells.

scholarly journals Divergent effects of quercetin conjugates on angiogenesis

2006 ◽  
Vol 95 (5) ◽  
pp. 1016-1023 ◽  
Author(s):  
Sandra Donnini ◽  
Federica Finetti ◽  
Lorenzo Lusini ◽  
Lucia Morbidelli ◽  
Veronique Cheynier ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Inhibitory Effect ◽  
Endothelial Cell Proliferation ◽  
Vegf Receptor ◽  
Cell Functions ◽  
Extracellular Signal ◽  
Opposing Effects ◽  
Endothelial Growth Factor

The present study reports the activities of quercetin and its main circulating conjugates in man (quercetin-3′-sulphate (Q3′S) and quercetin-3-glucuronide (Q3G)) on in vivo angiogenesis induced by vascular endothelial growth factor (VEGF) and examines the effects of these molecules on cultured endothelial cells. We found opposing effects of quercetin and its metabolites on angiogenesis. While quercetin and Q3G inhibited VEGF-induced endothelial cell functions and angiogenesis, Q3′S per se promoted endothelial cell proliferation and angiogenesis. The inhibitory effect elicited by Q3G was linked to inhibition of extracellular signal-regulated kinases 1/2 (ERK1/2) phosphorylation elicited by VEGF. The activation of endothelial cells by Q3′S was associated to stimulation of VEGF receptor-2 and to downstream signalling activation (phosphatidylinositol-3 kinase/Akt and nitric oxide synthase pathways), ultimately responsible for ERK1/2 phosphorylation. These data indicate that the effects of circulating quercetin conjugates on angiogenesis are different depending on the nature of the conjugate. Q3G andQ3′S are the two major conjugates in plasma, but their ratio is dependenton several factors, so thatinhibition or activation of angiogenesis could be subtly shifted as a result of metabolismin vivo.

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