Identification of peptides lead capable to potently change the proliferation and migration of endothelial cells

• 80 Peptides
• 5 nmol peptide per well
• Catalog No.: L-008A,
• Version No.: 002A
• Price: $4400.00/Library

	Peptide Name M.W   Peptide Name M.W 1 Tetrastatin-1 2352.79 41 Hexastatin-3 2447.89 2 Tetrastatin-3 2097.39 42 Vasostatin I (17-76) (Human) 6811.83 3 Pentastatin-3 2090.31 43 Vasostatin I (17-43) (Human) 3009.52 4 Thrombostatin con-3 2080.31 44 Vasostatin I / Prepro-Chromogranin A (19-94) (Human) 8553.9 5 Chemokinostatin-7 2535.09 45 Vasostatin II, C-terminal / Prepro-Chromogranin A (97-131)  3908.13 6 Chemokinostatin-8 2802.25 46 Fractalkine(CX3CL1) Chemokine Domain (1-80) (Human) 9053.82 7 Semastatin-5A.1 2102.39 47 Secretoneurin 3652.01 8 Semastatin-5B 2041.21 48 Thymosin Beta4 4963.55 9 Properdistatin 2177.50 49 Amphiregulin C-terminal 4794.38 10 Scospondistatin 2023.19 50 Relaxin II 5963.02 11 Chemokinostatin-1 2625.20 51 Endostatin (52-114)-Amide / JKC362 (Human) 6985 12 Chemokinostatin-3 2395.96 52 Ela-32 3967.87 13 Chemokinostatin-5 2612.13 53 T3 peptide /Tumstatin(69-88) 2407.85 14 Chemokinostatin-6 2684.20 54 T7 peptide /Tumstatin(74-98) 3018.83 15 Semastatin-5A.2 2099.40 55 Apelin-13 1550.85 16 Nephroblastostatin 1951.24 56 SCNH2/Selective Cutting Apelin-36 (1-16)-amide (Human) 1704.9 17 Wispostatin-1 1838.10 57 ANGPTL 3 (140-220) (Human) 9519.95 18 Thrombostatin con-1 2192.43 58 ANGPTL 4 (97-160) (Human) 7555.66 19 Netrinstatin-5C 2287.57 59 UN-1/ Thrombin Preproprotein (354-363) (Human) 1193.29 20 Thrombostatin con-6, Cyclic Cys4 and Cys8 1884.13 60 UN-2/ Thrombin Preproprotein (315-327) (Human) 1560.27 21 Wispostatin-2 1812.13 61 UN-3 2834.08 22 Wispostatin-3 1997.35 62 SDF-1 (human) 7606.01 23 Papilostatin-1 1694.83 63 PEDF-34 / Prepro-PEDF (44-77) (Human) 3763.26 24 Papilostatin-2 2100.33 64 PEDF-43 / Prepro-PEDF (79-121) (Human) 4582.58 25 Hexastatin-2 2547.86 65 PEDF-44 / prepro PEDF (78-121) (Human) 4680.25 26 Spondinstatin-1 2187.47 66 Neurotensin (8-13) [Lys8, Asn9] / LANT-6 746.44 27 Connectostain 1917.22 67 Neurotensin, Acetyl (8-13) 858.55 28 Cyrostatin 1902.14 68 PR-39 4725 29 Netrinstatin-5D 2280.58 69 Apelin-13 (Human) 1550.05 30 Fibulostatin-6.1 2094.45 70 Cyclo(1-6)CRPRLCKHcyclo(9-14)CRPRLC 1737.41 31 Fibulostatin-6.2 1940.16 71 MM07 / Cyclo(1-6)CRPRLCHKGPMPF 1539.91 32 Fibulostatin-6.3 2053.27 72 Endostatin (133-180)-Amide / Endostain derived E4 (Human) 2053.27 33 Cartilostatin-1 2124.39 73 Octanoylated ghrelin (Human) 3372 34 Cartilostatin-2 2055.38 74 LL-37 (Human) 4493.36 35 Adamtsostatin-4 1957.14 75 Defensin 2, beta (Human) 4328.27 36 Adamtsostatin-16 1724.90 76 Elabela (Human) 3950.87 37 Adamtsostatin-18 2145.41 77 ELA-21 (Mouse) 2668.18 38 Adamtsostatin-like 4 2333.65 78 WKYMVm 856.11 39 Complestatin-C6 2168.36 79 Vasotide Control peptide 416.57 40 Tetrastatin-2 2569.87 80 Vasotide 588.76

PEDF and 34-mer inhibit angiogenesis in the heart by inducing tip cells apoptosis via up-regulating PPAR-γ to increase surface FasL.

Pigment epithelial-derived factor (PEDF) is a potent anti-angiogenic factor whose effects are partially mediated through the induction of endothelial cell apoptosis. However, the underlying mechanism for PEDF and the functional PEDF peptides 34-mer and 44-mer to inhibit angiogenesis in the heart has not been fully established. In the present study, by constructing adult Sprague-Dawley rat models of acute myocardial infarction (AMI) and in vitro myocardial angiogenesis, we showed that PEDF and 34-mer markedly inhibits angiogenesis by selectively inducing tip cells apoptosis rather than quiescent cells. Peptide 44-mer on the other hand exhibits no such effects. Next, we identified Fas death pathway as essential downstream regulators of PEDF and 34-mer activities in inhibiting angiogenesis. By using peroxisome proliferator-activated receptor γ (PPAR-γ) siRNA and PPAR-γ inhibitor, GW9662, we found the effects of PEDF and 34-mer were extensively blocked. These data suggest that PEDF and 34-mer inhibitangiogenesis via inducing tip cells apoptosis at least by means of up-regulating PPAR-γ to increase surface FasL in the ischemic heart, which might be a novel mechanism to understanding cardiac angiogenesis after AMI.

Zhang H, Wei T, Jiang X et al., Apoptosis. 2015 Oct 30. [Epub ahead of print]

Serelaxin: A Novel Therapy for Acute Heart Failure with a Range of Hemodynamic and Non-Hemodynamic Actions.

Acute heart failure (AHF) is characterized by high morbidity and mortality and high costs. Although the treatment of AHF has not changed substantially in recent decades, it is becoming clear that treatment strategies for AHF need to address both the immediate hemodynamic abnormalities giving rise to congestion as well as prevent organ damage that can influence long-term prognosis. Serelaxin, the recombinant form of human relaxin-2, a naturally occurring peptide hormone, has been found to significantly improve symptoms and signs of AHF, prevent in-hospital worsening heart failure, as well as significantly improve 180-day cardiovascular and all-cause mortality after a 48-h infusion commenced within 16 h of presentation (RELAX-AHF study). Available data suggest that the clinical benefits may be attributable to a potential combination of multiple actions of serelaxin, including improving systemic, cardiac, and renal hemodynamics, and protecting cells and organs from damage via anti-inflammatory, anti-cell death, anti-fibrotic, anti-hypertrophic, and pro-angiogenic effects. This manuscript describes the short- and long-term effects of serelaxin in AHF patients, analyzing how these effects can be explained by taking into account the range of hemodynamic and non-hemodynamic actions of serelaxin. In addition, this paper also addresses several aspects related to the role of serelaxin in the therapy of AHF that remain to be clarified and warrant further investigation

Díez J. Am J Cardiovasc Drugs. 2014 Mar 4. [Epub ahead of print]

PEDF Expression Regulates the Pro-angiogenic and Pro-inflammatory Phenotype of the Lung Endothelium.

Pigment epithelium-derived factor (PEDF) is a multifunctional protein with important roles in regulation of inflammation and angiogenesis. It is produced by various cell types including endothelial cells (EC). However, the cell autonomous impact of PEDF on EC function needs further investigation. Lung EC prepared from PEDF-deficient (PEDF -/-) mice were more migratory and failed to undergo capillary morphogenesis in Matrigel compared with wild type (PEDF +/+) EC. Although no significant differences were observed in the rates of apoptosis in PEDF -/- EC compared with PEDF +/+ cells under basal or stress conditions, PEDF -/- EC proliferated at a slower rate. PEDF -/- EC also expressed increased levels of proinflammatory markers including vascular endothelial growth factor, inducible nitric oxide synthase, vascular cell adhesion molecule-1, as well as altered cellular junctional organization, and nuclear localization of β-catenin. The PEDF -/- EC were also more adhesive, expressed decreased levels of thrombospondin-2, tenascin-C and osteopontin, and increased fibronectin. Furthermore, we showed lungs from PEDF -/- mice exhibited increased expression of macrophage marker F4/80 along with increased thickness of the vascular walls consistent with a pro-inflammatory phenotype. Together our data suggest that the PEDF expression makes significant contribution to modulation of the inflammatory and angiogenic phenotype of the lung endothelium.

Shin ES, Sorenson CM, Sheibani N. Am J Physiol Lung Cell Mol Physiol. 2013 Dec 6. [Epub ahead of print]

Verifiable hypotheses for thymosin β4-dependent and -independent angiogenic induction of Trichinella spiralis-triggered nurse cell formation.

Trichinella spiralis has been reported to induce angiogenesis for nutrient supply and waste disposal by the induction of the angiogenic molecule vascular endothelial cell growth factor (VEGF) during nurse cell formation. However, the action mechanism to induce VEGF in nurse cells by T. spiralis is not known. Hypoxia in nurse cells was suggested as a possible mechanism; however, the presence of hypoxic conditions in infected muscle or nurse cells and whether hypoxia indeed induces the expression of VEGF and subsequent angiogenesis in the infected muscle are both a matter of debate. Our recent studies have shown that thymosin β4, a potent VEGF inducing protein, is expressed in the very early stages of T. spiralis muscle infection suggesting the induction of VEGF in early stage nurse cells. Nevertheless, we now show that hypoxic conditions were not detected in any nurse cell stage but were detected only in the accumulated inflammatory cells. These studies propose that induction of angiogenesis by VEGF in T. spiralis-infected nurse cells was mediated by thymosin β4 and is unrelated to hypoxic conditions

Ock MS, Cha HJ, Choi YH, Int J Mol Sci. 2013 Nov 29;14(12):23492-8. doi: 10.3390/ijms141223492.

A new chromogranin A-dependent angiogenic switch activated by thrombin.

Angiogenesis, the formation of blood vessels from pre-existing vasculature, is regulated by a complex interplay of anti and proangiogenic factors. We found that physiologic levels of circulating chromogranin A (CgA), a protein secreted by the neuroendocrine system, can inhibit angiogenesis in various in vitro and in vivo experimental models. Structure-activity studies showed that a functional anti-angiogenic site is located in the C-terminal region, whereas a latent anti-angiogenic site, activated by cleavage of Q76-K77 bond, is present in the N-terminal domain. Cleavage of CgA by thrombin abrogated its anti-angiogenic activity and generated fragments (lacking the C-terminal region) endowed of potent proangiogenic activity. Hematologic studies showed that biologically relevant levels of forms of full-length CgA and CgA1-76 (anti-angiogenic) and lower levels of fragments lacking the C-terminal region (proangiogenic) are present in circulation in healthy subjects. Blood coagulation caused, in a thrombin-dependent manner, almost complete conversion of CgA into fragments lacking the C-terminal region. These results suggest that the CgA-related circulating polypeptides form a balance of anti and proangiogenic factors tightly regulated by proteolysis. Thrombin-induced alteration of this balance could provide a novel mechanism for triggering angiogenesis in pathophysiologic conditions characterized by prothrombin activation.

Crippa L, Bianco M, Colombo B et al., Blood. 2013 Jan 10;121(2):392-402. doi: 10.1182/blood-2012-05-430314. Epub 2012 Nov 27.

The angiogenic factor secretoneurin induces coronary angiogenesis in a model of myocardial infarction by stimulation of vascular endothelial growth factor signaling in endothelial cells.

BACKGROUND:
Secretoneurin is a neuropeptide located in nerve fibers along blood vessels, is upregulated by hypoxia, and induces angiogenesis. We tested the hypothesis that secretoneurin gene therapy exerts beneficial effects in a rat model of myocardial infarction and evaluated the mechanism of action on coronary endothelial cells.

METHODS AND RESULTS:
In vivo secretoneurin improved left ventricular function, inhibited remodeling, and reduced scar formation. In the infarct border zone, secretoneurin induced coronary angiogenesis, as shown by increased density of capillaries and arteries. In vitro secretoneurin induced capillary tubes, stimulated proliferation, inhibited apoptosis, and activated Akt and extracellular signal-regulated kinase in coronary endothelial cells. Effects were abrogated by a vascular endothelial growth factor (VEGF) antibody, and secretoneurin stimulated VEGF receptors in these cells. Secretoneurin furthermore increased binding of VEGF to endothelial cells, and binding was blocked by heparinase, indicating that secretoneurin stimulates binding of VEGF to heparan sulfate proteoglycan binding sites. Additionally, secretoneurin increased binding of VEGF to its coreceptor neuropilin-1. In endothelial cells, secretoneurin also stimulated fibroblast growth factor receptor-3 and insulin-like growth factor-1 receptor, and in coronary vascular smooth muscle cells, we observed stimulation of VEGF receptor-1 and fibroblast growth factor receptor-3. Exposure of cardiac myocytes to hypoxia and ischemic heart after myocardial infarction revealed increased secretoneurin messenger RNA and protein.

CONCLUSIONS:
Our data show that secretoneurin acts as an endogenous stimulator of VEGF signaling in coronary endothelial cells by enhancing binding of VEGF to low-affinity binding sites and neuropilin-1 and stimulates further growth factor receptors like fibroblast growth factor receptor-3. Our in vivo findings indicate that secretoneurin may be a promising therapeutic tool in ischemic heart disease.

Albrecht-Schgoer K, Schgoer W, Holfeld J, et al., Circulation. 2012 Nov 20;126(21):2491-501. doi: 10.1161/CIRCULATIONAHA.111.076950. Epub 2012 Oct 18.

The role of angiopoietin-like proteins in angiogenesis and metabolism.

Recently, a family of proteins structurally similar to the angiogenic regulating factors angiopoietins was identified and designated "angiopoietin-like proteins" (Angptls). Encoded by seven genes, Angptls 1 to 7 all possess an N-terminal coiled-coil domain and a C-terminal fibrinogen-like domain, both characteristic of angiopoietins. However, Angptls do not bind to either the angiopoietin receptor Tie2 or the related protein Tie1 and remain orphan ligands. Nonetheless, Angptls 1, 2, 3, 4, and Angptl6/angiopoietin-related growth factor function to regulate angiogenesis. Angptls 3, 4, and Angptl6/angiopoietin-related growth factor also appear to directly regulate lipid, glucose, and energy metabolism independently of angiogenic effects. Recently, several lines of evidence reveal differential roles of Angptl structural domains in both angiogenesis and metabolism. Here, we briefly review what is currently known about Angptls function.

Hato T, Tabata M, Oike Y. Trends Cardiovasc Med. 2008 Jan;18(1):6-14. doi: 10.1016/j.tcm.2007.10.003.

Anti-angiogenic peptides identified in thrombospondin type I domains.

Thrombospondin 1, the prototypical protein of the thrombospondin protein family, is a potent endogenous inhibitor of angiogenesis. Although the effects of the thrombospondin 1 on neovascularization have been well studied, little is known about the anti-angiogenic potency of other proteins or peptide fragments derived from the proteins in this family. Here we identify a set of 18 novel, anti-angiogenic 17- to 20-amino acid peptides that are derived from proteins containing type I thrombospondin motifs. We have named these peptides adamtsostatin-4, adamtsostatin-16, adamtsostatin-18, cartilostatin-1, cartilostatin-2, fibulostatin-6.2, fibulostatin-6.3, papilostatin-1, papilostatin-2, properdistatin, scospondistatin, semastatin-5A.1, semastatin-5A.2, semastatin-5B, thrombostatin containing-1, thrombostatin contaning-3, thrombostatin contaning-6, and wispostatin-1 to reflect their origin. We further demonstrate that these peptides inhibit the proliferation and migration of human umbilical vein endothelial cells in vitro. The anti-proliferative and anti-migratory properties of the identified peptides may be important in maintaining angiogenic homeostasis in vivo and make these peptides suitable candidates for use as anti-angiogenic pharmaceutical agents in numerous therapeutic applications.

Karagiannis ED, Popel AS. Biochem Biophys Res Commun. 2007 Jul 20;359(1):63-9. Epub 2007 May 14.

Angiogenesis--a new target for future therapy.

Development of blood vessels from in situ differentiating endothelial cells (EC) is called vasculogenesis, whereas sprouting of new blood vessels from the pre-existing ones is termed angiogenesis or neovascularisation. Angiogenesis, the growth of new blood vessels, is essential during tissue repair, foetal development, and female reproductive cycle. In contrast, uncontrolled angiogenesis promotes tumor and retinopathies, while inadequate angiogenesis can lead to coronary artery disease. A balance between pro-angiogenic and anti-angiogenic growth factors and cytokines tightly controls angiogenesis. With the identification of several proangiogenic molecules such as the vascular endothelial cell growth factor (VEGF), the fibroblast growth factors (FGFs), and the angiopoietins, and the recent description of specific inhibitors of angiogenesis such as platelet factor-4, angiostatin, endostatin, and vasostatin, it is recognized that therapeutic interference with vasculature formation offers a tool for clinical applications in various pathologies. Inhibition of angiogenesis can prevent diseases such as cancer, diabetic nephropathy, arthritis, psoriasis, whereas stimulation of angiogenesis is beneficial in the treatment of coronary artery disease (CAD), cardiac failure, tissue injury, etc. One of the most specific and critical regulators of angiogenesis is vascular endothelial growth factor (VEGF), which regulates endothelial proliferation, permeability, and survival. Substantial evidence also implicates VEGF as an angiogenic mediator in tumors and intraocular neovascular syndromes, and numerous clinical trials are presently testing the hypothesis that inhibition of VEGF may have therapeutic value

Pandya NM, Dhalla NS, Santani DD. Vascul Pharmacol. 2006 May;44(5):265-74. Epub 2006 Mar 20.

Stimulation of cell-surface urokinase-type plasminogen activator activity and cell migration in vascular endothelial cells by a novel hexapeptide analogue of neurotensin.

To investigate if neurotensin (NT) could induce activation of urokinase-type plasminogen activator (uPA) in vascular endothelial cells, we utilized the acetyl-NT (8-13) analogue, TJN-950, in which the C-terminal leucine is reduced to leucinol. TJN-950 inhibited the binding of 125I-NT to membranes of newborn rat brains and of COS-7 cells transfected with rat NT receptor cDNA, but at 10(4) higher doses than NT (8-13). However, TJN-950 was as effective as NT in inducing the fibrinolytic activity in bovine vascular aortic and human umbilical vein endothelial cells, and enhanced the migration of vascular endothelial cells. Moreover, administration of TJN-950 induced neovascularization in the rat cornea in vivo. TJN-950 had no effect on expression of uPA, plasminogen activator inhibitor-1 or uPA receptor mRNA. The binding of 125I-TJN-950 to cell membranes was blocked by unlabeled uPA and TJN-950, but not the amino-terminal or 12-32 fragment of uPA. TJN-950 may enhance uPA activity in vascular endothelial cells by interacting with the uPA receptor, resulting in induction of angiogenesis.

Ushiro S, Mizoguchi K, Yoshida S, et al., FEBS Lett. 1997 Dec 1;418(3):341-5.