Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Proteomic profiling of endothelial cell secretomes after exposure to calciprotein particles reveals downregulation of basement membrane assembly and increased release of soluble CD59. / Степанов, Александр; Шишкова, Дарья; Маркова, Виктория; Маркова, Юлия; Фролов, Алексей ; Лазебная , Анастасия ; Ощепкова , Екатерина ; Переплетчикова, Дарья ; Смирнова , Дарья; Басович , Любовь ; Репкин, Егор Алексеевич; Кутихин, Антон.
в: International Journal of Molecular Sciences, Том 25, № 21, 11382, 23.10.2024.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Proteomic profiling of endothelial cell secretomes after exposure to calciprotein particles reveals downregulation of basement membrane assembly and increased release of soluble CD59
AU - Степанов, Александр
AU - Шишкова, Дарья
AU - Маркова, Виктория
AU - Маркова, Юлия
AU - Фролов, Алексей
AU - Лазебная , Анастасия
AU - Ощепкова , Екатерина
AU - Переплетчикова, Дарья
AU - Смирнова , Дарья
AU - Басович , Любовь
AU - Репкин, Егор Алексеевич
AU - Кутихин, Антон
PY - 2024/10/23
Y1 - 2024/10/23
N2 - Calciprotein particles (CPPs) are essential circulating scavengers of excessive Ca 2+ and PO 4 3- ions, representing a vehicle that removes them from the human body and precludes extraskeletal calcification. Having been internalised by endothelial cells (ECs), CPPs induce their dysfunction, which is accompanied by a remarkable molecular reconfiguration, although little is known about this process's extracellular signatures. Here, we applied ultra-high performance liquid chromatography-tandem mass spectrometry to perform a secretome-wide profiling of the cell culture supernatant from primary human coronary artery ECs (HCAECs) and internal thoracic artery ECs (HITAECs) treated with primary CPPs (CPP-P), secondary CPPs (CPP-S), magnesiprotein particles (MPPs), or Ca 2+/Mg 2+-free Dulbecco's phosphate-buffered saline (DPBS) for 24 h. Incubation with CPP-P/CPP-S significantly altered the profiles of secreted proteins, delineating physiological and pathological endothelial secretomes. Neither pathway enrichment analysis nor the interrogation of protein-protein interactions detected extracellular matrix- and basement membrane-related molecular terms in the protein datasets from CPP-P/CPP-S-treated ECs. Both proteomic profiling and enzyme-linked immunosorbent assay identified an increased level of protectin (CD59) and reduced levels of osteonectin (SPARC), perlecan (HSPG2), and fibronectin (FN1) in the cell culture supernatant upon CPP-P/CPP-S treatment. Elevated soluble CD59 and decreased release of basement membrane components might be considered as potential signs of dysfunctional endothelium.
AB - Calciprotein particles (CPPs) are essential circulating scavengers of excessive Ca 2+ and PO 4 3- ions, representing a vehicle that removes them from the human body and precludes extraskeletal calcification. Having been internalised by endothelial cells (ECs), CPPs induce their dysfunction, which is accompanied by a remarkable molecular reconfiguration, although little is known about this process's extracellular signatures. Here, we applied ultra-high performance liquid chromatography-tandem mass spectrometry to perform a secretome-wide profiling of the cell culture supernatant from primary human coronary artery ECs (HCAECs) and internal thoracic artery ECs (HITAECs) treated with primary CPPs (CPP-P), secondary CPPs (CPP-S), magnesiprotein particles (MPPs), or Ca 2+/Mg 2+-free Dulbecco's phosphate-buffered saline (DPBS) for 24 h. Incubation with CPP-P/CPP-S significantly altered the profiles of secreted proteins, delineating physiological and pathological endothelial secretomes. Neither pathway enrichment analysis nor the interrogation of protein-protein interactions detected extracellular matrix- and basement membrane-related molecular terms in the protein datasets from CPP-P/CPP-S-treated ECs. Both proteomic profiling and enzyme-linked immunosorbent assay identified an increased level of protectin (CD59) and reduced levels of osteonectin (SPARC), perlecan (HSPG2), and fibronectin (FN1) in the cell culture supernatant upon CPP-P/CPP-S treatment. Elevated soluble CD59 and decreased release of basement membrane components might be considered as potential signs of dysfunctional endothelium.
KW - Basement Membrane/metabolism
KW - Cells, Cultured
KW - Coronary Vessels/metabolism
KW - Down-Regulation/drug effects
KW - Endothelial Cells/metabolism
KW - Fibronectins/metabolism
KW - Heparan Sulfate Proteoglycans/metabolism
KW - Humans
KW - Osteonectin/metabolism
KW - Proteome/metabolism
KW - Proteomics/methods
KW - Secretome/metabolism
KW - Tandem Mass Spectrometry
KW - endothelial cells
KW - basement membrane
KW - proteomic profiling
KW - bioinformatic analysis
KW - endothelial dysfunction
KW - endothelial secretome
KW - calcium stress
KW - CD59
KW - calciprotein particles
KW - extracellular matrix
UR - https://www.mendeley.com/catalogue/8fdcd2f2-dc80-3712-9a8a-872325edca50/
U2 - 10.3390/ijms252111382
DO - 10.3390/ijms252111382
M3 - Article
C2 - 39518935
VL - 25
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1422-0067
IS - 21
M1 - 11382
ER -
ID: 126354091