Sialyl LewisX mimic-decorated liposomes for anti-angiogenic everolimus delivery to E-selectin expressing endothelial cells

Abstract Kallikrein-12 (KLK12) may play an important role in angiogenesis modulating proangiogenic factor bioavailability and activating the kinin receptor B2 pathway. We studied whether KLK12 had an impact on angiogenesis and the activation of kinin receptor B2 results from the KLK12-dependent generation of kinins. KLK12 efficiently hydrolyzed high molecular weight kininogen, liberating a fragment containing the carboxy-terminal end of kinins. The kininogenase activity of KLK12 was poor, however, due to the cleavage resistance of the N-terminal side of the kinin sequence. A very low amount of kinins was accordingly released after in vitro incubation of high molecular weight kininogen with KLK12 and thus the proangiogenic activity of KLK12 in lung endothelial cells was not related to a kinin release.

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Autophagy Is a Potential Target for Enhancing the Anti-Angiogenic Effect of Mebendazole in Endothelial Cells

Biomolecules & Therapeutics ◽

10.4062/biomolther.2018.222 ◽

2019 ◽

Vol 27 (1) ◽

pp. 117-125 ◽

Cited By ~ 4

Author(s):

So Jung Sung ◽

Hyun-Kyung Kim ◽

Yong-Kil Hong ◽

Young Ae Joe

Keyword(s):

Endothelial Cells ◽

Potential Target ◽

Angiogenic Effect

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Abstract P211: N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) Promotes Tube Formation in Human Coronary Artery Endothelial Cells

Hypertension ◽

10.1161/hyp.68.suppl_1.p211 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Ginette Bordcoch ◽

Pablo Nakagawa ◽

Cesar A Romero ◽

Oscar A Romero

Keyword(s):

Endothelial Cells ◽

Coronary Artery ◽

Capillary Tube ◽

Tube Formation ◽

Endothelial Cell Migration ◽

Tube Length ◽

Human Coronary Artery ◽

Double Phase ◽

Angiogenic Effect

Ac-SDKP is an endogenous peptide with anti-inflammation and anti-fibrotic effects in hypertensive and cardiovascular diseases. It is cleaved from Thymosin β4 (Tβ4) and hydrolyzed by angiotensin converting enzyme (ACE). Ac-SDKP plasma concentration increases after treatment with ACE inhibitors (ACEi) and some of the beneficial effects of ACEi treatment has been ascribed to Ac-SDKP. Ac-SDKP is a mediator of angiogenesis in in-vitro and in-vivo animal models. Ac-SDKP stimulates rodents derived immortalized aortic endothelial cells migration and capillary-like structures formation (tube formation). Similarly, Ac-SDKP increases capillary density after myocardial infarction in rats. The mechanism related to angiogenesis induced by Ac-SDKP is not known. Tβ4 (Ac-SDKP precursor) promotes endothelial cell migration and angiogenesis by the activation of the VEGF/AKT pathway. Our objective is to evaluate the Ac-SDKP pro-angiogenic effect in Human Coronary Artery Endothelial Cells (HCAEC) and the mechanism that regulates the angiogenic effect of Ac-SDKP. HCAEC do not produce VEGF, thus we hypothesize that Ac-SDKP increases VEGF expression in fibroblasts and that indirectly could promote capillary tube formation in endothelial cells. We used primary culture of rat cardiac fibroblast (RCF) and we treated these cells with 10nM Ac-SDKP for 24 hours. VEGF concentration in cell supernatant was measured by ELISA. Cells were starved without serum overnight before the Ac-SDKP treatment. For capillary tube formation assay, HCAEC cells were seeded into matrigel and incubated in presence of 10nM Ac-SDKP for 12 hours, pictures were taken by double phase contrast microscope and tube length was quantified with image J software and the results were expressed as percentage of control. After Ac-SDKP treatment, VEGF concentration did not increase in the supernatant of RCF (control: 0.12±0.07 vs. Ac-SDKP: 0.14±0.09 mg/ml; p=0.7). However, Ac-SDKP treatment induced the development of tube formation in HCAECs by 7±2% respect to control (p=0.037). We conclude that Ac-SDKP induces capillary tube formation not only in rodent but also in human derived endothelial cells. The mechanism by which Ac-SDKP promotes tube formation in HCAECs is still unknown.

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The anti-angiogenic effect of tryptanthrin is mediated by the inhibition of apelin promoter activity and shortened mRNA half-life in human vascular endothelial cells

Phytomedicine ◽

10.1016/j.phymed.2019.152879 ◽

2019 ◽

Vol 58 ◽

pp. 152879 ◽

Cited By ~ 2

Author(s):

Hsin-Ning Chang ◽

Yuan-Chieh Yeh ◽

Ho-Yen Chueh ◽

Jong-Hwei S. Pang

Keyword(s):

Endothelial Cells ◽

Half Life ◽

Promoter Activity ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Angiogenic Effect ◽

Mrna Half Life

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MicroRNA-210 Plays a Critical Role in the Angiogenic Effect of Isoprenaline on Human Umbilical Vein Endothelial Cells via Regulation of Noncoding RNAs

Chinese Medical Journal ◽

10.4103/0366-6999.193452 ◽

2016 ◽

Vol 129 (22) ◽

pp. 2676-2682 ◽

Cited By ~ 6

Author(s):

You-You Yan ◽

Zhi-Hui Wang ◽

Lei Zhao ◽

Dan-Dan Song ◽

Chao Qi ◽

...

Keyword(s):

Endothelial Cells ◽

Umbilical Vein ◽

Critical Role ◽

Noncoding Rnas ◽

Human Umbilical Vein ◽

Angiogenic Effect ◽

Umbilical Vein Endothelial Cells

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Exosomes derived from induced vascular progenitor cells promote angiogenesis in vitro and in an in vivo rat hindlimb ischemia model

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00247.2019 ◽

2019 ◽

Vol 317 (4) ◽

pp. H765-H776 ◽

Cited By ~ 7

Author(s):

Takerra K. Johnson ◽

Lina Zhao ◽

Dihan Zhu ◽

Yang Wang ◽

Yan Xiao ◽

...

Keyword(s):

Endothelial Cells ◽

Progenitor Cells ◽

Ex Vivo ◽

Aortic Ring ◽

Size Exclusion ◽

Hindlimb Ischemia ◽

Vascular Progenitor Cells ◽

Angiogenic Effect

Induced vascular progenitor cells (iVPCs) were created as an ideal cell type for regenerative medicine and have been reported to positively promote collateral blood flow and improve cardiac function in a rat model of myocardial ischemia. Exosomes have emerged as a novel biomedicine that mimics the function of the donor cells. We investigated the angiogenic activity of exosomes from iPVCs (iVPC-Exo) as a cell-free therapeutic approach for ischemia. Exosomes from iVPCs and rat aortic endothelial cells (RAECs) were isolated using a combination of ultrafiltration and size-exclusion chromatography. Nanoparticle tracking analysis revealed that exosome isolates fell within the exosomal diameter (<150 nm). These exosomes contained known markers Alix and TSG101, and their morphology was validated using transmission electron microscopy. When compared with RAECs, iVPCs significantly increased the secretion of exosomes. Cardiac microvascular endothelial cells and aortic ring explants were pretreated with RAEC-Exo or iVPC-Exo, and basal medium was used as a control. iVPC-Exo exerted an in vitro angiogenic effect on the proliferation, tube formation, and migration of endothelial cells and stimulated microvessel sprouting in an ex vivo aortic ring assay. Additionally, iVPC-Exo increased blood perfusion in a hindlimb ischemia model. Proangiogenic proteins (pentraxin-3 and insulin-like growth factor-binding protein-3) and microRNAs (-143-3p, -291b, and -20b-5p) were found to be enriched in iVPC-Exo, which may mediate iVPC-Exo induced vascular growth. Our findings demonstrate that treatment with iVPC-Exo promotes angiogenesis in vitro, ex vivo, and in vivo. Collectively, these findings indicate a novel cell-free approach for therapeutic angiogenesis. NEW & NOTEWORTHY The results of this work demonstrate exosomes as a novel physiological mechanism by which induced vascular progenitor cells exert their angiogenic effect. Moreover, angiogenic cargo of proteins and microRNAs may define the biological contributors in activating endothelial cells to form a new capillary plexus for ischemic vascular diseases. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/angiogenic-exosomes-from-vascular-progenitor-cells/ .

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Indigo naturalis and its component tryptanthrin exert anti-angiogenic effect by arresting cell cycle and inhibiting Akt and FAK signaling in human vascular endothelial cells

Journal of Ethnopharmacology ◽

10.1016/j.jep.2015.08.050 ◽

2015 ◽

Vol 174 ◽

pp. 474-481 ◽

Cited By ~ 23

Author(s):

Hsin-Ning Chang ◽

Sheng-Teng Huang ◽

Yuan-Chieh Yeh ◽

Hsin-Shih Wang ◽

Tzu-Hao Wang ◽

...

Keyword(s):

Cell Cycle ◽

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Angiogenic Effect ◽

Indigo Naturalis

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Inhibition of endothelial cell migration by thrombospondin-1 type-1 repeats is mediated by β1 integrins

The Journal of Cell Biology ◽

10.1083/jcb.200407060 ◽

2005 ◽

Vol 168 (4) ◽

pp. 643-653 ◽

Cited By ~ 94

Author(s):

Sarah M. Short ◽

Alexandrine Derrien ◽

Radha P. Narsimhan ◽

Jack Lawler ◽

Donald E. Ingber ◽

...

Keyword(s):

Endothelial Cells ◽

Umbilical Vein ◽

Endothelial Cell Migration ◽

Vegf Receptor ◽

Β1 Integrins ◽

Thrombospondin 1 ◽

Angiogenic Effect ◽

Phosphoinositide 3 Kinase ◽

Umbilical Vein Endothelial Cells

The anti-angiogenic effect of thrombospondin-1 has been shown to be mediated through binding of the type-1 repeat (TSR) domain to the CD36 transmembrane receptor. We now report that the TSR domain can inhibit VEGF-induced migration in human umbilical vein endothelial cells (HUVEC), cells that lack CD36. Moreover, we identified β1 integrins as a critical receptor in TSR-mediated inhibition of migration in HUVEC. Using pharmacological inhibitors of downstream VEGF receptor effectors, we found that phosphoinositide 3-kinase (PI3k) was essential for TSR-mediated inhibition of HUVEC migration, but that neither PLCγ nor Akt was necessary for this response. Furthermore, β1 integrins were critical for TSR-mediated inhibition of microvascular endothelial cells, cells that express CD36. Together, our results indicate that β1 integrins mediate the anti-migratory effects of TSR through a PI3k-dependent mechanism.

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