The long coiled-coil protein NECC2 regulates oxLDL-induced endothelial oxidative damage and exacerbates atherosclerosis development in apolipoprotein E -/- mice
Copyright © 2024 Elsevier Inc. All rights reserved..
Oxidized low density lipoprotein (oxLDL)-induced endothelial oxidative damage promotes the development of atherosclerosis. Caveolae play an essential role in maintaining the survival and function of vascular endothelial cell (VEC). It is reported that the long coiled-coil protein NECC2 is localized in caveolae and is associated with neural cell differentiation and adipocyte formation, but its role in VECs needs to be clarified. Our results showed NECC2 expression increased in the endothelium of plaque-loaded aortas and oxLDL-treated HUVECs. Down-regulation of NECC2 by NECC2 siRNA or compound YF-307 significantly inhibited oxLDL-induced VEC apoptosis and the adhesion factors expression. Remarkably, inhibition of NECC2 expression in the endothelium of apoE-/- mice by adeno-associated virus (AAV)-carrying NECC2 shRNA or compound YF-307 alleviated endothelium injury and restricted atherosclerosis development. The immunoprecipitation results confirmed that NECC2 interacted with Tyk2 and caveolin-1(Cav-1) in VECs, and NECC2 further promoted the phosphorylation of Cav-1 at Tyr14 b y activating Tyk2 phosphorylation. On the other hand, inhibiting NECC2 levels suppressed oxLDL-induced phosphorylation of Cav-1, uptake of oxLDL by VECs, accumulation of intracellular reactive oxygen species and activation of NF-κB. Our findings suggest that NECC2 may contribute to oxLDL-induced VEC injury and atherosclerosis via modulating Cav-1 phosphorylation through Tyk2. This work provides a new concept and drug target for treating atherosclerosis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:216 |
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| Enthalten in: |
Free radical biology & medicine - 216(2024) vom: 28. Apr., Seite 106-117 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mu, Xin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.04.2024 Date Revised 12.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.freeradbiomed.2024.03.001 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 4 | |a The long coiled-coil protein NECC2 regulates oxLDL-induced endothelial oxidative damage and exacerbates atherosclerosis development in apolipoprotein E -/- mice |
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| 520 | |a Oxidized low density lipoprotein (oxLDL)-induced endothelial oxidative damage promotes the development of atherosclerosis. Caveolae play an essential role in maintaining the survival and function of vascular endothelial cell (VEC). It is reported that the long coiled-coil protein NECC2 is localized in caveolae and is associated with neural cell differentiation and adipocyte formation, but its role in VECs needs to be clarified. Our results showed NECC2 expression increased in the endothelium of plaque-loaded aortas and oxLDL-treated HUVECs. Down-regulation of NECC2 by NECC2 siRNA or compound YF-307 significantly inhibited oxLDL-induced VEC apoptosis and the adhesion factors expression. Remarkably, inhibition of NECC2 expression in the endothelium of apoE-/- mice by adeno-associated virus (AAV)-carrying NECC2 shRNA or compound YF-307 alleviated endothelium injury and restricted atherosclerosis development. The immunoprecipitation results confirmed that NECC2 interacted with Tyk2 and caveolin-1(Cav-1) in VECs, and NECC2 further promoted the phosphorylation of Cav-1 at Tyr14 b y activating Tyk2 phosphorylation. On the other hand, inhibiting NECC2 levels suppressed oxLDL-induced phosphorylation of Cav-1, uptake of oxLDL by VECs, accumulation of intracellular reactive oxygen species and activation of NF-κB. Our findings suggest that NECC2 may contribute to oxLDL-induced VEC injury and atherosclerosis via modulating Cav-1 phosphorylation through Tyk2. This work provides a new concept and drug target for treating atherosclerosis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Atherosclerosis | |
| 650 | 4 | |a Long coiled-coil proteins | |
| 650 | 4 | |a Oxidized low-density lipoprotein | |
| 650 | 4 | |a Vascular endothelial cell | |
| 650 | 7 | |a Apolipoproteins |2 NLM | |
| 650 | 7 | |a Apolipoproteins E |2 NLM | |
| 650 | 7 | |a Lipoproteins, LDL |2 NLM | |
| 650 | 7 | |a oxidized low density lipoprotein |2 NLM | |
| 650 | 7 | |a Jakmip3 protein, mouse |2 NLM | |
| 700 | 1 | |a Liu, Shu-Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Lei-Yin |e verfasserin |4 aut | |
| 700 | 1 | |a Ouyang, Chenxi |e verfasserin |4 aut | |
| 700 | 1 | |a Abdalla, Ahmed M E |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xin-Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Fei-Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Ning |e verfasserin |4 aut | |
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