VEGF121 and VEGF165 Regulate Blood Vessel Diameter Through Vascular Endothelial Growth Factor Receptor 2 in an in vitro Angiogenesis Model

Nakatsu, Martin N.; Sainson, Richard C.A.; Pérez‐del‐Pulgar, Sofía; Aoto, Jason; Aitkenhead, Mark; Taylor, K. L.; Carpenter, Philip M.; Hughes, Christopher C.W.

doi:10.1097/01.lab.0000107160.81875.33

Cited by 128 publications

(118 citation statements)

References 59 publications

(71 reference statements)

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“…In islets, VEGF-A constitutively secreted from beta cells has been shown to be crucial for the early formation, branching and maintenance of the vascular network [9,22,23]. VEGF-A may, however, also directly increase the capillary diameter through the VEGF2 receptor [24]. Interestingly, our gene expression studies identified increased expression of Vegfa in microsphere-containing islets, providing a likely mechanism for their higher vascular density and increased capillary width.…”

Section: Discussionmentioning

confidence: 62%

Superior beta cell proliferation, function and gene expression in a subpopulation of rat islets identified by high blood perfusion

et al. 2012

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Aims/hypothesis The blood perfusion of individual pancreatic islets is highly variable, with a subgroup of islets having high perfusion and blood vessels responsive to further blood flow increase induced by glucose. This study tested the hypothesis that there is heterogeneity between islets with regard to beta cell proliferation, function and gene expression based on differences in their blood perfusion. Methods Fluorescent microspheres were injected into the ascending aorta, and then microsphere-containing and nonmicrosphere-containing pancreatic islets were isolated for investigation. By this procedure, the 5% of islets with the greatest blood perfusion were identified for study. Islet endothelial cells were isolated separately to investigate the role of improved vascular support in the observed differences. Results The vascular network was found to be more dense and tortuous in microsphere-containing than other islets. The most highly blood-perfused islets also had a higher rate of beta cell proliferation, superior beta cell function and a markedly different gene expression from other islets. Cultured islets exposed to islet endothelial cell products had a similarly increased beta cell proliferation rate, yet significantly fewer changes in gene expression than observed in the most highly blood-perfused islets.Conclusions/interpretation A novel heterogeneity between islets was observed, with superior beta cell proliferation, function and gene expression in a subpopulation of islets identified by high blood perfusion. In contrast with a previously described population of low-oxygenated, sleeping islets, which are recruited into functionality when needed, the presently described heterogeneity is shown to remain in vitro after islet isolation.

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Section: Discussionmentioning

confidence: 62%

Superior beta cell proliferation, function and gene expression in a subpopulation of rat islets identified by high blood perfusion

et al. 2012

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“…This circumferential growth occurs both within the arterial and venous branch of the vasculature and crucially increases blood flow toward and from capillary beds, respectively. Defects in angiogenic sprouting frequently lead to a strong increase in vessel diameter, presumably because additional ECs are incorporated into the wall of existing tubes and are no longer directed into new sprouts and branches (Ruhrberg et al 2002;Nakatsu et al 2003;Erber et al 2006). Such phenotypes suggest that the balance between endothelial proliferation and new sprouting might also be a determinant of the normal circumferential growth seen in larger blood vessels and, particularly, in arteries and veins.…”

Section: Angiogenic Remodeling Of Blood Vesselsmentioning

confidence: 99%

Regulation of vascular morphogenesis by Notch signaling

Roca¹,

Adams²

2007

Genes Dev.

395

312

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The Notch pathway is a versatile regulator of cell fate specification, growth, differentiation, and patterning processes in metazoan organisms. In the vertebrate cardiovascular system, multiple Notch family receptors and several of their Jagged and Delta-like ligands are expressed during critical stages of embryonic and postnatal development. Functional studies in mice, fish, tumor models, and cell culture systems have shown that the angiogenic growth of the blood vessel network, the proliferation of endothelial cells, and the differentiation of arteries and veins are controlled by Notch signaling. Moreover, Notch pathway components play important roles in human pathological conditions involving the vasculature, namely CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) and Alagille syndrome. Recent findings highlight the Notch ligand Delta-like 4 as a key regulator of tumor angiogenesis and suggest that this protein might be a promising target for cancer therapy.

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“…productive system (36) and it is well established that angiogenic cytokines, such as VEGF (68) and a number VEGF is the most studied and characterized angiogenic cytokine. In addition to coordinating endothelial of other growth and trophic factors, are present in the testis and are secreted by intratesticular Sertoli cells cell and pericyte interactions (25), it regulates blood vessel size during formation (37). Upregulation of VEGF (23).…”

Section: Angiogenic Cytokine Antibody Arraymentioning

confidence: 99%

“…Typically, transplantation success relies on aggressive and chronic immunosuppresRecently, efforts in angiogenic research have been directed toward the use of stem cells and cell therapeutics sion, exposing the individual to serious and potentially life-threatening consequences. If rejection does not oc- (37). Repair of severely damaged organs and/or damaged systems have been attempted with the use of cell cur immediately, successful engraftment occurs only if the cells or tissues are completely and adequately vascutherapies such as cell transplantation (19,26,28,31,46).…”

Section: Introductionmentioning

confidence: 99%

“…Because Sertoli cells also seendothelial growth factor (VEGF) (25,34,37,39,40,45,50), basic fibroblast growth factor (bFGF) (4,30,31,67), crete angiogenic factors (13,23), it is possible that SC ET retain this functional ability and stimulate neovasculariplatelet-derived growth factor (PDGF) (40), insulin-like growth factor-1 (IGF-1) (40), fractalkine (9,63), and tuzation of newly transplanted cells and tissues, thereby enhancing graft survival and transplantation protocol mor necrosing factor-α (TNF-α) (1,29,32,67). Increasing the amounts of these types of growth factors at the efficacy.…”

Section: Introductionmentioning

confidence: 99%

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Sertoli Cells Enhance Formation of Capillary-Like Structures in Vitro

Golat

Cameron

2008

Cell Transplant

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Sertoli cells isolated from the testis (referred to as extratesticular Sertoli cells) have been shown to facilitate allo-and xenogeneic cell transplantations. It appears likely that the ability of these cells to enhance the success of cell engraftment is due, in part, to the retention of their intratesticular functions of trophic support and immunoprotection. Sertoli cells also are involved in the regulation of angiogenesis in the testis, which may also contribute to enhanced cell engraftment success facilitated by extratesticular Sertoli cells. Because the maintenance of the cell's intratesticular angiogenic function has not yet been evaluated for extratesticular Sertoli cells, this study examined the cell's ability to enhance angiogenesis in vitro. Sertoli cell conditioned media were derived from isolated rat Sertoli cell cultures and used in a rat aortic model of induced angiogenesis, in endothelial and smooth muscle cell monocultures, and in endothelial smooth muscle cocultures. An angiogenic rat cytokine array identified angiogenic factors in the control and conditioned media. Aorta sections incubated with Sertoli cell conditioned media showed a marked increase in the formation of capillary-like structures when compared to controls. Likewise, endothelial cells incubated in conditioned media organized into capillary-like structures not observed when incubated in control media. In coculture, smooth muscle cells were associated with endothelial cell-derived capillary-like structures only when incubated in conditioned media. Cytokine arrays indicated the presence and a qualitative increase of specific angiogenic growth factors in Sertoli cell conditioned media not observed in control media. Results indicate that extratesticular Sertoli cells retain their intratesticular angiogenic function in vitro.

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VEGF121 and VEGF165 Regulate Blood Vessel Diameter Through Vascular Endothelial Growth Factor Receptor 2 in an in vitro Angiogenesis Model

Cited by 128 publications

References 59 publications

Superior beta cell proliferation, function and gene expression in a subpopulation of rat islets identified by high blood perfusion

Superior beta cell proliferation, function and gene expression in a subpopulation of rat islets identified by high blood perfusion

Regulation of vascular morphogenesis by Notch signaling

Sertoli Cells Enhance Formation of Capillary-Like Structures in Vitro

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