Islet Graft Survival and Function: Concomitant Culture and Transplantation With Vascular Endothelial Cells in Diabetic Rats

Background: Clinicians may choose to administer antiplatelet medications to patients with cerebral aneurysms following endovascular coiling to prevent thrombus formation and vascular occlusion, if they fear a thrombus will form on the platinum wire where it diverges into the vessel from the aneurysm sac. However, the mechanism by which vascular endothelial cells repair a vessel in the living body in the event of a coil deviation and the effects of antiplatelet drugs on these cells have not been fully elucidated. We aimed to investigate the association between endothelial progenitor cells (EPCs) and endothelium formation at the surface of the platinum coils deployed in the carotid artery of rats, and to determine the effects of different antiplatelet drugs on this process. Subjects and Methods: We established an experimental model using normal and diabetic rats at 12 months of age. The diabetic rats were assigned to 4 different diet groups, distinguished by whether they were fed plain rat feed, or the same feed supplemented by 1 of 3 antiplatelet drugs (cilostazol, aspirin, or clopidogrel: all 0.1%) for 2 weeks, and the carotid artery was perforated by an embolization coil (“carotid coil model”). We monitored the process by which vascular endothelial cells formed the new endothelium on the surface of the coil by sampling and evaluating the region at 1, 2, and 4 weeks after placement. This repair process was also compared among 3 groups treated with different antiplatelet drugs (i.e. aspirin, clopidogrel, and cilostazol). One-way analysis of variance tests were performed to evaluate the differences in vascular thickness between groups, and P < .05 was considered statistically significant. Results: The diabetic rats showed delayed neoendothelialization and marked intimal hyperplasia. Cilostazol and clopidogrel effectively counteracted this delayed endothelial repair process. Flk1 immunostaining revealed greater expression in the diabetic rats administered cilostazol, second only to normal rats, suggesting that this agent acted to recruit EPCs. Conclusion: Neoendothelialization is delayed when vascular endothelial cells fail to function normally, which consequently leads to the formation of hyperplastic tissue. Cilostazol may remedy this dysfunction by recruiting EPCs to the site of injury.

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Gravity Spun Polycaprolactone Fibers for Applications in Vascular Tissue Engineering: Proliferation and Function of Human Vascular Endothelial Cells

Tissue Engineering ◽

10.1089/ten.2006.12.45 ◽

2006 ◽

Vol 12 (1) ◽

pp. 45-51 ◽

Cited By ~ 24

Author(s):

Matthew R. Williamson ◽

Kevin J. Woollard ◽

Helen R. Griffiths ◽

Allan G.A. Coombes

Keyword(s):

Tissue Engineering ◽

Endothelial Cells ◽

Vascular Tissue ◽

Vascular Endothelial Cells ◽

Vascular Tissue Engineering ◽

Vascular Endothelial ◽

And Function

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Functional Role of TRPV4-K Ca 2.3 Signaling in Vascular Endothelial Cells in Normal and Streptozotocin-Induced Diabetic Rats

Hypertension ◽

10.1161/hypertensionaha.113.01500 ◽

2013 ◽

Vol 62 (1) ◽

pp. 134-139 ◽

Cited By ~ 57

Author(s):

Xin Ma ◽

Juan Du ◽

Peng Zhang ◽

Jianxin Deng ◽

Jie Liu ◽

...

Keyword(s):

Endothelial Cells ◽

Functional Role ◽

Vascular Endothelial Cells ◽

Diabetic Rats ◽

Vascular Endothelial

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Limits of isolation and culture: intact vascular endothelium and BKCa

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00042.2009 ◽

2009 ◽

Vol 297 (1) ◽

pp. H1-H7 ◽

Cited By ~ 60

Author(s):

Shaun L. Sandow ◽

T. Hilton Grayson

Keyword(s):

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Physiological Role ◽

Vascular Endothelial ◽

Experimental Conditions ◽

Disease States ◽

Vasoactive Substances ◽

Channel Expression ◽

Calcium Activated Potassium Channels ◽

And Function

The potential physiological role of plasmalemmal large-conductance calcium-activated potassium channels (BKCa) in vascular endothelial cells is controversial. Studies of freshly isolated and cultured vascular endothelial cells provide disparate results, both supporting and refuting a role for BKCa in endothelial function. Most studies using freshly isolated, intact, healthy arteries provide little support for a physiological role for BKCa in the endothelium, although recent work suggests that this may not be the case in diseased vessels. In isolated and cultured vascular endothelial cells, the autocrine action of growth factors, hormones, and vasoactive substances results in phenotypic drift. Such an induced heterogeneity is likely a primary factor accounting for the apparent differences, and often enhanced BKCa expression and function, in isolated and cultured vascular endothelial cells. In a similar manner, heterogeneity in endothelial BKCa expression and function in intact arteries may be representative of normal and disease states, BKCa being absent in normal intact artery endothelium and upregulated in disease where dysfunction induces signals that alter channel expression and function. Indeed, in some intact vessels, there is evidence for the presence of BKCa, such as mRNA and/or specific BK subunits, an observation that is consistent with the potential for rapid upregulation, as may occur in disease. This perspective proposes that the disparity in the results obtained for BKCa expression and function from freshly isolated and cultured vascular endothelial cells is largely due to variability in experimental conditions and, furthermore, that the expression of BKCa in intact artery endothelium is primarily associated with disease. Although answers to physiologically relevant questions may only be available in atypical physiological conditions, such as those of isolation and culture, the limitations of these methods require open and objective recognition.

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Osteostat/Tumor Necrosis Factor Superfamily 18 Inhibits Osteoclastogenesis and Is Selectively Expressed by Vascular Endothelial Cells

Endocrinology ◽

10.1210/en.2005-0518 ◽

2006 ◽

Vol 147 (1) ◽

pp. 70-78 ◽

Cited By ~ 14

Author(s):

Bernardetta Nardelli ◽

Liubov Zaritskaya ◽

William McAuliffe ◽

Yansong Ni ◽

Clint Lincoln ◽

...

Keyword(s):

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Early Stage ◽

Osteoclast Differentiation ◽

Precursor Cells ◽

In Vitro Assays ◽

Vascular Endothelial ◽

Tnf Superfamily ◽

And Function

Vascular endothelial cells (EC) participate in the process of bone formation through the production of factors regulating osteoclast differentiation and function. In this study, we report the selective expression in primary human microvascular EC of Osteostat/TNF superfamily 18, a ligand of the TNF superfamily. Osteostat protein is detectable in human microvascular EC and is highly up-regulated by IFN-α and IFN-β. Moreover, an anti-Osteostat antibody strongly binds to the vascular endothelium in human tissues, demonstrating that the protein is present in the EC layers surrounding blood vessels. Functional in vitro assays were used to define Osteostat involvement in osteoclastogenesis. Both recombinant and membrane-bound Osteostat inhibit differentiation of osteoclasts from monocytic precursor cells. Osteostat suppresses the early stage of osteoclastogenesis via inhibition of macrophage colony-stimulating factor-induced receptor activator of NF-κB (RANK) expression in the osteoclast precursor cells. This effect appears to be specific for the differentiation pathway of the osteoclast lineage, because Osteostat does not inhibit lipopolysaccharide-induced RANK expression in monocytes and dendritic cells, or activation-induced RANK expression in T cells. These findings demonstrate that Osteostat is a novel regulator of osteoclast generation and substantiate the major role played by the endothelium in bone physiology.

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Revascularization Determines Volume Retention and Gene Expression by Fat Grafts in Mice

Experimental Biology and Medicine ◽

10.1177/153537020523001007 ◽

2005 ◽

Vol 230 (10) ◽

pp. 742-748 ◽

Cited By ~ 76

Author(s):

Motoko Yamaguchi ◽

Fumiaki Matsumoto ◽

Hideaki Bujo ◽

Manabu Shibasaki ◽

Kazuo Takahashi ◽

...

Keyword(s):

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Angiogenesis Inhibitor ◽

Vascular Endothelial ◽

Fat Grafts ◽

Expression Of Genes ◽

Autologous Fat Transplantation ◽

And Function ◽

Volume Retention ◽

Graft Volume

Autologous fat transplantation is a popular and useful technique in plastic and reconstructive surgery. The efficiency and survival of such grafts is predictable in many cases, but there are still issues to be resolved, such as how to improve graft volume retention. To address the issue of volume retention, we studied the effect of revascularization from the recipient on the size and function of adipocytes in fat grafts. Treatment of mice with TNP-470, an angiogenesis inhibitor, reduced blood flow from the recipient into the graft after subcutaneous transplantation of epididymal fat. The weight of transplanted tissues and the size of adipocytes in the grafts were significantly lower in mice treated with TNP-470 (TNP mice) than in control mice. Expression of genes for enzymes related to lipid accumulation was decreased in the grafts of TNP mice compared with control mice. Moreover, the expression of adipocyte-derived angiogenic peptides, VEGF and leptin, was significantly lower in the grafts of TNP mice than in grafts from control animals. The expression of VEGF and leptin by cultured human adipocytes was increased in the presence of conditioned medium from cultured vascular endothelial cells. These results show that the inhibition of the revascularization of fat grafts after transplantation reduces graft volume retention and cellular function. Early and adequate revascularization may be important for both the supply of nutrients and vasoactive interactions between vascular endothelial cells and adipocytes in graft.

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