Calciprotein Particles Induce Endothelial Dysfunction by Impairing Endothelial Nitric Oxide Metabolism
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| Názov: | Calciprotein Particles Induce Endothelial Dysfunction by Impairing Endothelial Nitric Oxide Metabolism |
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| Autori: | Lian Feenstra, Anton G. Kutikhin, Daria K. Shishkova, Hendrik Buikema, Lara W. Zeper, Arno R. Bourgonje, Guido Krenning, Jan-Luuk Hillebrands |
| Zdroj: | Arterioscler Thromb Vasc Biol Arteriosclerosis, Thrombosis, and Vascular Biology, 43, 3, pp. 443-455 |
| Informácie o vydavateľovi: | Ovid Technologies (Wolters Kluwer Health), 2023. |
| Rok vydania: | 2023 |
| Predmety: | 0301 basic medicine, Nitric Oxide Synthase Type III, Nitrites/metabolism, Basic Sciences, Swine, Radboudumc 11: Renal disorders Physiology, Radboud University Medical Center, Nitric Oxide Synthase Type III/metabolism, Vascular/metabolism, Chronic/metabolism, Nitric Oxide, 3. Good health, 03 medical and health sciences, Nitric Oxide/metabolism, Endothelium/metabolism, Human Umbilical Vein Endothelial Cells, Humans, Animals, Renal Insufficiency, Endothelium, Vascular Diseases, Endothelium, Vascular, Renal Insufficiency, Chronic, Human Umbilical Vein Endothelial Cells/metabolism, Nitrites |
| Popis: | Background: Calciprotein particles (CPPs) are associated with the development of vascular calcifications in chronic kidney disease. The role of endothelial cells (ECs) in this process is unknown. Here, we investigated the interaction of CPPs and ECs, thereby focusing on endothelial nitric oxide metabolism and oxidative stress. Methods: CPPs were generated in calcium- and phosphate-enriched medium. Human umbilical vein endothelial cells were exposed to different concentrations of CPPs (0–100 µg/mL) for 24 or 72 hours. Ex vivo porcine coronary artery rings were used to measure endothelial cell–dependent vascular smooth muscle cell relaxation after CPP exposure. Serum samples from an early chronic kidney disease cohort (n=245) were analyzed for calcification propensity (measure for CPP formation) and nitrate and nitrite levels (NO x ). Results: CPP exposure for 24 hours reduced eNOS (endothelial nitric oxide synthase) mRNA expression and decreased nitrite production, indicating reduced nitric oxide bioavailability. Also, 24-hour CPP exposure caused increased mitochondria-derived superoxide generation, together with nitrotyrosine protein residue formation. Long-term (72 hours) exposure of human umbilical vein endothelial cells to CPPs induced eNOS uncoupling and decreased eNOS protein expression, indicating further impairment of the nitric oxide pathway. The ex vivo porcine coronary artery model showed a significant reduction in endothelial-dependent vascular smooth muscle cell relaxation after CPP exposure. A negative association was observed between NO x levels and calcification propensity (r=−0.136; P =0.049) in sera of (early) chronic kidney disease patients. Conclusions: CPPs cause endothelial cell dysfunction by impairing nitric oxide metabolism and generating oxidative stress. Our findings provide new evidence for direct effects of CPPs on ECs and pathways involved. |
| Druh dokumentu: | Article Other literature type |
| Jazyk: | English |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/atvbaha.122.318420 |
| Prístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/36727521 https://hdl.handle.net/https://repository.ubn.ru.nl/handle/2066/290928 https://doi.org/10.1161/ATVBAHA.122.318420 https://hdl.handle.net/11370/90d73f28-0a4e-4d0e-a0d9-0c4b8e94e6bd https://research.rug.nl/en/publications/90d73f28-0a4e-4d0e-a0d9-0c4b8e94e6bd https://doi.org/10.1161/ATVBAHA.122.318420 https://repository.ubn.ru.nl/handle/2066/290928 https://repository.ubn.ru.nl//bitstream/handle/2066/290928/290928.pdf |
| Rights: | CC BY NC ND URL: http://creativecommons.org/licenses/by-nc-nd/4.0/Arteriosclerosis, Thrombosis, and Vascular Biology is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made. |
| Prístupové číslo: | edsair.doi.dedup.....38bfbca6e9228468b480f8442f8c7f3f |
| Databáza: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Background: Calciprotein particles (CPPs) are associated with the development of vascular calcifications in chronic kidney disease. The role of endothelial cells (ECs) in this process is unknown. Here, we investigated the interaction of CPPs and ECs, thereby focusing on endothelial nitric oxide metabolism and oxidative stress. Methods: CPPs were generated in calcium- and phosphate-enriched medium. Human umbilical vein endothelial cells were exposed to different concentrations of CPPs (0–100 µg/mL) for 24 or 72 hours. Ex vivo porcine coronary artery rings were used to measure endothelial cell–dependent vascular smooth muscle cell relaxation after CPP exposure. Serum samples from an early chronic kidney disease cohort (n=245) were analyzed for calcification propensity (measure for CPP formation) and nitrate and nitrite levels (NO x ). Results: CPP exposure for 24 hours reduced eNOS (endothelial nitric oxide synthase) mRNA expression and decreased nitrite production, indicating reduced nitric oxide bioavailability. Also, 24-hour CPP exposure caused increased mitochondria-derived superoxide generation, together with nitrotyrosine protein residue formation. Long-term (72 hours) exposure of human umbilical vein endothelial cells to CPPs induced eNOS uncoupling and decreased eNOS protein expression, indicating further impairment of the nitric oxide pathway. The ex vivo porcine coronary artery model showed a significant reduction in endothelial-dependent vascular smooth muscle cell relaxation after CPP exposure. A negative association was observed between NO x levels and calcification propensity (r=−0.136; P =0.049) in sera of (early) chronic kidney disease patients. Conclusions: CPPs cause endothelial cell dysfunction by impairing nitric oxide metabolism and generating oxidative stress. Our findings provide new evidence for direct effects of CPPs on ECs and pathways involved. |
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| ISSN: | 15244636 10795642 |
| DOI: | 10.1161/atvbaha.122.318420 |