Effect of Sphingomyelinase-Treated LDLs on HUVECs
Low-density lipoproteins (LDLs) exert a key role in the transport of esterified cholesterol to tissues. Among the atherogenic modifications of LDLs, the oxidative modification has been mainly investigated as a major risk factor for accelerating atherogenesis. Since LDL sphingolipids are also emergin...
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| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/5/2100 |
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| author | Angelica Giuliani Camilla Morresi Gabriele Mazzuferi Luisa Bellachioma Deborah Ramini Jacopo Sabbatinelli Fabiola Olivieri Tiziana Bacchetti Gianna Ferretti |
| author_facet | Angelica Giuliani Camilla Morresi Gabriele Mazzuferi Luisa Bellachioma Deborah Ramini Jacopo Sabbatinelli Fabiola Olivieri Tiziana Bacchetti Gianna Ferretti |
| author_sort | Angelica Giuliani |
| collection | DOAJ |
| description | Low-density lipoproteins (LDLs) exert a key role in the transport of esterified cholesterol to tissues. Among the atherogenic modifications of LDLs, the oxidative modification has been mainly investigated as a major risk factor for accelerating atherogenesis. Since LDL sphingolipids are also emerging as important regulators of the atherogenic process, increasing attention is devoted to the effects of sphingomyelinase (SMase) on LDL structural and atherogenic properties. The aims of the study were to investigate the effect of SMase treatment on the physical-chemical properties of LDLs. Moreover, we evaluated cell viability, apoptosis, and oxidative and inflammatory status in human umbilical vein endothelial cells (HUVECs) treated with either ox-LDLs or SMase-treated LDLs (SMase-LDLs). Both treatments were associated with the accrual of the intracellular ROS and upregulation of the antioxidant Paraoxonase 2 (PON2), while only SMase-LDLs induced an increase of superoxide dismutase 2 (SOD2), suggesting the activation of a feedback loop to restrain the detrimental effects of ROS. The increased caspase-3 activity and reduced viability observed in cells treated with SMase-LDLs and ox-LDLs suggest a pro-apoptotic effect of these modified lipoproteins on endothelial cells. Moreover, a strong proinflammatory effect of SMase-LDLs compared to ox-LDLs was confirmed by an increased activation of NF-κB and consequent increased expression of its downstream cytokines IL-8 and IL-6 in HUVECs. |
| first_indexed | 2024-03-11T07:17:53Z |
| format | Article |
| id | doaj.art-af916c246ea445e8a4aa3da520425ec6 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T07:17:53Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-af916c246ea445e8a4aa3da520425ec62023-11-17T08:12:06ZengMDPI AGMolecules1420-30492023-02-01285210010.3390/molecules28052100Effect of Sphingomyelinase-Treated LDLs on HUVECsAngelica Giuliani0Camilla Morresi1Gabriele Mazzuferi2Luisa Bellachioma3Deborah Ramini4Jacopo Sabbatinelli5Fabiola Olivieri6Tiziana Bacchetti7Gianna Ferretti8Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, ItalyDepartment of Life and Environmental Science, Polytechnic University of Marche, 60100 Ancona, ItalyDepartment of Clinical Science, Polytechnic University of Marche, 60100 Ancona, ItalyDepartment of Life and Environmental Science, Polytechnic University of Marche, 60100 Ancona, ItalyClinic of Laboratory and Precision Medicine, IRCCS INRCA, 60121 Ancona, ItalyDepartment of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, ItalyDepartment of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, ItalyDepartment of Life and Environmental Science, Polytechnic University of Marche, 60100 Ancona, ItalyDepartment of Clinical Science, Polytechnic University of Marche, 60100 Ancona, ItalyLow-density lipoproteins (LDLs) exert a key role in the transport of esterified cholesterol to tissues. Among the atherogenic modifications of LDLs, the oxidative modification has been mainly investigated as a major risk factor for accelerating atherogenesis. Since LDL sphingolipids are also emerging as important regulators of the atherogenic process, increasing attention is devoted to the effects of sphingomyelinase (SMase) on LDL structural and atherogenic properties. The aims of the study were to investigate the effect of SMase treatment on the physical-chemical properties of LDLs. Moreover, we evaluated cell viability, apoptosis, and oxidative and inflammatory status in human umbilical vein endothelial cells (HUVECs) treated with either ox-LDLs or SMase-treated LDLs (SMase-LDLs). Both treatments were associated with the accrual of the intracellular ROS and upregulation of the antioxidant Paraoxonase 2 (PON2), while only SMase-LDLs induced an increase of superoxide dismutase 2 (SOD2), suggesting the activation of a feedback loop to restrain the detrimental effects of ROS. The increased caspase-3 activity and reduced viability observed in cells treated with SMase-LDLs and ox-LDLs suggest a pro-apoptotic effect of these modified lipoproteins on endothelial cells. Moreover, a strong proinflammatory effect of SMase-LDLs compared to ox-LDLs was confirmed by an increased activation of NF-κB and consequent increased expression of its downstream cytokines IL-8 and IL-6 in HUVECs.https://www.mdpi.com/1420-3049/28/5/2100sphingomyelinaseceramidelow-density lipoproteinoxidative stress |
| spellingShingle | Angelica Giuliani Camilla Morresi Gabriele Mazzuferi Luisa Bellachioma Deborah Ramini Jacopo Sabbatinelli Fabiola Olivieri Tiziana Bacchetti Gianna Ferretti Effect of Sphingomyelinase-Treated LDLs on HUVECs Molecules sphingomyelinase ceramide low-density lipoprotein oxidative stress |
| title | Effect of Sphingomyelinase-Treated LDLs on HUVECs |
| title_full | Effect of Sphingomyelinase-Treated LDLs on HUVECs |
| title_fullStr | Effect of Sphingomyelinase-Treated LDLs on HUVECs |
| title_full_unstemmed | Effect of Sphingomyelinase-Treated LDLs on HUVECs |
| title_short | Effect of Sphingomyelinase-Treated LDLs on HUVECs |
| title_sort | effect of sphingomyelinase treated ldls on huvecs |
| topic | sphingomyelinase ceramide low-density lipoprotein oxidative stress |
| url | https://www.mdpi.com/1420-3049/28/5/2100 |
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