In Vitro Angiogenic Effects of Pancreatic Bile Salt-Dependent Lipase

Rebaï, Ouafa; Petit-Thévenin, Josette Le; Bruneau, Nadine; Lagadic‐Gossmann, Dominique; Vérine, Alain

doi:10.1161/01.atv.0000151618.49109.bd

Cited by 23 publications

(13 citation statements)

References 34 publications

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“…Alternatively, BSDL, which has a heparin-binding site (16) and a V3-like loop domain (17), associates with intestinal cell-surface proteoglycans (7,8). In vitro studies have shown that BSDL induces vascular smooth muscle cell proliferation and evokes endothelial cell proliferation and chemotactic migration (13,18). However, the function of circulating plasma pancreatic BSDL is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Bile salt–dependent lipase interacts with platelet CXCR4 and modulates thrombus formation in mice and humans

Panicot‐Dubois¹,

Thomas²,

Furie³

et al. 2007

J. Clin. Invest.

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Bile salt-dependent lipase (BSDL) is an enzyme involved in the duodenal hydrolysis and absorption of cholesteryl esters. Although some BSDL is transported to blood, the role of circulating BSDL is unknown. Here, we demonstrate that BSDL is stored in platelets and released upon platelet activation. Because BSDL contains a region that is structurally homologous to the V3 loop of HIV-1, which binds to CXC chemokine receptor 4 (CXCR4), we hypothesized that BSDL might bind to CXCR4 present on platelets. In human platelets in vitro, both BSDL and a peptide corresponding to its V3-like loop induced calcium mobilization and enhanced thrombin-mediated platelet aggregation, spreading, and activated α IIb β 3 levels. These effects were abolished by CXCR4 inhibition. BSDL also increased the production of prostacyclin by human endothelial cells. In a mouse thrombosis model, BSDL accumulated at sites of vessel wall injury. When CXCR4 was antagonized, the accumulation of BSDL was inhibited and thrombus size was reduced. In BSDL -/-mice, calcium mobilization in platelets and thrombus formation were attenuated and tail bleeding times were increased in comparison with those of wild-type mice. We conclude that BSDL plays a role in optimal platelet activation and thrombus formation by interacting with CXCR4 on platelets.

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Section: Introductionmentioning

confidence: 99%

Bile salt–dependent lipase interacts with platelet CXCR4 and modulates thrombus formation in mice and humans

Panicot‐Dubois¹,

Thomas²,

Furie³

et al. 2007

J. Clin. Invest.

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“…[8][9][10]16 The amount of VEGF needed for biological activity in vitro and in vivo appears to be unclear. Amounts as small as 10 ng have shown biological effects in vitro, 17 whereas others used micrograms to induce biological effects of VEGF. 18,19 It is likely that the amount needed for biological effects on vascular development are dependent on factors such as type of VEGF, release profile, and animal model.…”

Section: Discussionmentioning

confidence: 99%

In Vitro and In Vivo Effects of Deoxyribonucleic Acid–Based Coatings Funtionalized with Vascular Endothelial Growth Factor

et al. 2007

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Vascularization is important in wound healing and essential for tissue ingrowth into porous tissue-engineering matrices. Furthermore, peri-implant tissue vascularization is known to be important for the functionality of subcutaneously implanted biosensors (e.g., glucose sensors). As a first exploration of the use of deoxyribonucleic acid (DNA)-based coatings for the optimization of biosensor functionality, this study focused on the effect of DNA-based coatings functionalized with vascular endothelial growth factor (VEGF) on in vitro endothelial cell behavior and vascularization of the peri-implant tissue in vivo. To that end, DNA-based coatings consisting of poly-D-lysine and DNA were functionalized with different amounts of VEGF (25 and 250 ng) and compared to non-coated controls and non-functionalized DNA-based coatings. The results demonstrated the superiority of VEGF-functionalized DNA-based coatings in increasing endothelial cell proliferation and migration in vitro over non-coated controls and non-functionalized DNA-based coatings. In vivo, a significant increase in vascularization of the peri-implant area was observed for VEGF-functionalized DNA-based coatings. Because no dosage-dependent effects were observed, future experiments should focus on optimizing VEGF concentration for this purpose. Additionally, the administration of VEGF in combination with other (pro-angiogenic) factors should be considered.

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“…In addition, well-known constituents of ZG such as RNAse A and carboxyl ester lipase (CEL) have the potential to interact with proteoglycans, e.g. to influence enzyme function (Dvorak & Morgan 1998, Rebaï et al 2005. Moreover, an interaction of the secretory lectin ZG16p (Cronshagen et al 1994, Kleene et al 1999) with heparan sulfate containing proteoglycans from ZG has recently been reported (Kumazawa-Inoue et al 2012).…”

Section: The Formation Of Zg In the Acinar Cells Is Initiated At The mentioning

confidence: 99%

Proteoglycans support proper granule formation in pancreatic acinar cells

Aroso

Agricola

Hacker

et al. 2015

Histochem Cell Biol

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Zymogen granules (ZG) are specialized organelles in the exocrine pancreas which allow digestive enzyme storage and regulated secretion. The molecular mechanisms of their biogenesis and the sorting of zymogens are still incompletely understood. Here, we investigated the role of proteoglycans in granule formation and secretion of zymogens in pancreatic AR42J cells, an acinar model system. Cupromeronic Blue cytochemistry and biochemical studies revealed an association of proteoglycans primarily with the granule membrane. Removal of proteoglycans by carbonate treatment led to a loss of membrane curvature indicating a supportive role in the maintenance of membrane shape and stability.Chemical inhibition of proteoglycan synthesis impaired the formation of normal electrondense granules in AR42J cells and resulted in the formation of unusually small granule structures. These structures still contained the zymogen carboxypeptidase, a cargo molecule of secretory granules, but migrated to lighter fractions after density gradient centrifugation.Furthermore, the basal secretion of amylase was increased in AR42J cells after inhibitor treatment. In addition, irregular-shaped granules appeared in pancreatic lobules. We conclude that the assembly of a proteoglycan scaffold at the ZG membrane is supporting efficient packaging of zymogens and the proper formation of stimulus-competent storage granules in acinar cells of the pancreas.Aroso et al.

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In Vitro Angiogenic Effects of Pancreatic Bile Salt-Dependent Lipase

Cited by 23 publications

References 34 publications

Bile salt–dependent lipase interacts with platelet CXCR4 and modulates thrombus formation in mice and humans

Bile salt–dependent lipase interacts with platelet CXCR4 and modulates thrombus formation in mice and humans

In Vitro and In Vivo Effects of Deoxyribonucleic Acid–Based Coatings Funtionalized with Vascular Endothelial Growth Factor

Proteoglycans support proper granule formation in pancreatic acinar cells

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