High phosphate directly affects endothelial function by downregulating annexin II
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High phosphate directly affects endothelial function by downregulating annexin II. / Di Marco, Giovana Seno; König, Maximilian; Stock, Christian; Wiesinger, Anne; Hillebrand, Uta; Reiermann, Stefanie; Reuter, Stefan; Amler, Susanne; Köhler, Gabriele; Buck, Friedrich; Fobker, Manfred; Kümpers, Philipp; Oberleithner, Hans; Hausberg, Martin; Lang, Detlef; Pavenstädt, Hermann; Brand, Marcus.
in: KIDNEY INT, Jahrgang 83, Nr. 2, 01.02.2013, S. 213-22.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - High phosphate directly affects endothelial function by downregulating annexin II
AU - Di Marco, Giovana Seno
AU - König, Maximilian
AU - Stock, Christian
AU - Wiesinger, Anne
AU - Hillebrand, Uta
AU - Reiermann, Stefanie
AU - Reuter, Stefan
AU - Amler, Susanne
AU - Köhler, Gabriele
AU - Buck, Friedrich
AU - Fobker, Manfred
AU - Kümpers, Philipp
AU - Oberleithner, Hans
AU - Hausberg, Martin
AU - Lang, Detlef
AU - Pavenstädt, Hermann
AU - Brand, Marcus
PY - 2013/2/1
Y1 - 2013/2/1
N2 - Hyperphosphatemia is associated with increased cardiovascular risk in patients with renal disease and in healthy individuals. Here we tested whether high phosphate has a role in the pathophysiology of cardiovascular events by interfering with endothelial function, thereby impairing microvascular function and angiogenesis. Protein expression analysis found downregulation of annexin II in human coronary artery endothelial cells, an effect associated with exacerbated shedding of annexin II-positive microparticles by the cells exposed to high phosphate media. EAhy926 endothelial cells exposed to sera from hyperphosphatemic patients also display decreased annexin II, suggesting a negative correlation between serum phosphate and annexin II expression. By using endothelial cell-based assays in vitro and the chicken chorioallantoic membrane assay in vivo, we found that angiogenesis, vessel wall morphology, endothelial cell migration, capillary tube formation, and endothelial survival were impaired in a hyperphosphatemic milieu. Blockade of membrane-bound extracellular annexin II with a specific antibody mimicked the effects of high phosphate. In addition, high phosphate stiffened endothelial cells in vitro and in rats in vivo. Thus, our results link phosphate and adverse clinical outcomes involving the endothelium in both healthy individuals and patients with renal disease.
AB - Hyperphosphatemia is associated with increased cardiovascular risk in patients with renal disease and in healthy individuals. Here we tested whether high phosphate has a role in the pathophysiology of cardiovascular events by interfering with endothelial function, thereby impairing microvascular function and angiogenesis. Protein expression analysis found downregulation of annexin II in human coronary artery endothelial cells, an effect associated with exacerbated shedding of annexin II-positive microparticles by the cells exposed to high phosphate media. EAhy926 endothelial cells exposed to sera from hyperphosphatemic patients also display decreased annexin II, suggesting a negative correlation between serum phosphate and annexin II expression. By using endothelial cell-based assays in vitro and the chicken chorioallantoic membrane assay in vivo, we found that angiogenesis, vessel wall morphology, endothelial cell migration, capillary tube formation, and endothelial survival were impaired in a hyperphosphatemic milieu. Blockade of membrane-bound extracellular annexin II with a specific antibody mimicked the effects of high phosphate. In addition, high phosphate stiffened endothelial cells in vitro and in rats in vivo. Thus, our results link phosphate and adverse clinical outcomes involving the endothelium in both healthy individuals and patients with renal disease.
KW - Animals
KW - Annexin A2
KW - Apoptosis
KW - Cell Movement
KW - Cells, Cultured
KW - Chick Embryo
KW - Down-Regulation
KW - Humans
KW - Hyperphosphatemia
KW - Male
KW - Neovascularization, Physiologic
KW - Proteomics
KW - Rats
KW - Rats, Sprague-Dawley
KW - Renal Insufficiency, Chronic
KW - Vascular Stiffness
U2 - 10.1038/ki.2012.300
DO - 10.1038/ki.2012.300
M3 - SCORING: Journal article
C2 - 22913982
VL - 83
SP - 213
EP - 222
JO - KIDNEY INT
JF - KIDNEY INT
SN - 0085-2538
IS - 2
ER -