Intervention time decides the status of autophagy, NLRP3 activity and apoptosis in macrophages induced by ox‐LDL
Abstract Background It has been determined through extensive studies that autophagy, the Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome and apoptotic responses in macrophages jointly contribute to atherogenesis and its development in the presen...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | Lipids in Health and Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12944-022-01714-x |
| _version_ | 1811257163155243008 |
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| author | Liang Zheng Hongbiao Xu Fufu Zheng Yuanhui Lai Jie Li Weiming Lv Zuojun Hu Wenjian Wang |
| author_facet | Liang Zheng Hongbiao Xu Fufu Zheng Yuanhui Lai Jie Li Weiming Lv Zuojun Hu Wenjian Wang |
| author_sort | Liang Zheng |
| collection | DOAJ |
| description | Abstract Background It has been determined through extensive studies that autophagy, the Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome and apoptotic responses in macrophages jointly contribute to atherogenesis and its development in the presence of lipid abnormalities. Few studies have investigated in full-scale if the intervention time for lipids abnormality or NLRP3 activation have a significant effect on autophagy, NLRP3 or the apoptotic status in macrophages. Methods Human THP-1 monocyte-derived macrophages were established by challenging THP-1 monocytes with 80 µg/ml oxidized low-density lipoprotein (ox-LDL) for specific durations. Foam cell formation was observed by Oil Red O (ORO) staining. Western blots were employed to determine protein expression. Transmission electron microscope (TEM) and immunofluorescence microscopy were applied to observe the autophagic status of cells. Cell apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Results The cells were treated with ox-LDL for 12 h and 36 h, which were considered to represent early and advanced stages of atherogenesis for this study. The results showed that inhibition of ox-LDL phagocytosis by cytochalasin D in the early stage improved autophagic status, reduced NLRP3 activation and the apoptotic response significantly. In contrast, cytochalasin D had little effect on blocking the detrimental effect of ox-LDL at the advanced stage. Moreover, the changes in autophagy, apoptosis and NLRP3 expression after treatment with small interfering (si) RNA targeting NLRP3 in the early and advanced stages of atherogenesis were consistent with the above data. Conclusions Interventions against lipid disorders or inflammatory reactions in the early or advanced stages of atherogenesis may have different results depending on when they are applied during the process of atherosclerotic pathogenesis. These results may help improve therapeutic strategies for atherosclerosis prevention. Furthermore, a healthy lifestyle should still be recommended as the most important and inexpensive measure to prevent atherogenesis. |
| first_indexed | 2024-04-12T17:53:02Z |
| format | Article |
| id | doaj.art-af4b5cedf2784bfaab1e1de5315a8393 |
| institution | Directory Open Access Journal |
| issn | 1476-511X |
| language | English |
| last_indexed | 2024-04-12T17:53:02Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Lipids in Health and Disease |
| spelling | doaj.art-af4b5cedf2784bfaab1e1de5315a83932022-12-22T03:22:27ZengBMCLipids in Health and Disease1476-511X2022-10-0121111110.1186/s12944-022-01714-xIntervention time decides the status of autophagy, NLRP3 activity and apoptosis in macrophages induced by ox‐LDLLiang Zheng0Hongbiao Xu1Fufu Zheng2Yuanhui Lai3Jie Li4Weiming Lv5Zuojun Hu6Wenjian Wang7Laboratory of Department of Surgery, the First Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Thyroid and Breast Surgery, the First Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Urology, the First Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Thyroid and Breast Surgery, the First Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Thyroid and Breast Surgery, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityDepartment of Thyroid and Breast Surgery, the First Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Vascular Surgery, the First Affiliated Hospital of Sun Yat-Sen UniversityLaboratory of Department of Surgery, the First Affiliated Hospital of Sun Yat-Sen UniversityAbstract Background It has been determined through extensive studies that autophagy, the Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome and apoptotic responses in macrophages jointly contribute to atherogenesis and its development in the presence of lipid abnormalities. Few studies have investigated in full-scale if the intervention time for lipids abnormality or NLRP3 activation have a significant effect on autophagy, NLRP3 or the apoptotic status in macrophages. Methods Human THP-1 monocyte-derived macrophages were established by challenging THP-1 monocytes with 80 µg/ml oxidized low-density lipoprotein (ox-LDL) for specific durations. Foam cell formation was observed by Oil Red O (ORO) staining. Western blots were employed to determine protein expression. Transmission electron microscope (TEM) and immunofluorescence microscopy were applied to observe the autophagic status of cells. Cell apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Results The cells were treated with ox-LDL for 12 h and 36 h, which were considered to represent early and advanced stages of atherogenesis for this study. The results showed that inhibition of ox-LDL phagocytosis by cytochalasin D in the early stage improved autophagic status, reduced NLRP3 activation and the apoptotic response significantly. In contrast, cytochalasin D had little effect on blocking the detrimental effect of ox-LDL at the advanced stage. Moreover, the changes in autophagy, apoptosis and NLRP3 expression after treatment with small interfering (si) RNA targeting NLRP3 in the early and advanced stages of atherogenesis were consistent with the above data. Conclusions Interventions against lipid disorders or inflammatory reactions in the early or advanced stages of atherogenesis may have different results depending on when they are applied during the process of atherosclerotic pathogenesis. These results may help improve therapeutic strategies for atherosclerosis prevention. Furthermore, a healthy lifestyle should still be recommended as the most important and inexpensive measure to prevent atherogenesis.https://doi.org/10.1186/s12944-022-01714-xAtherosclerosisAutophagyNucleotide-binding oligomerization domain-like receptor containing pyrin domain 3Apoptosis; oxidized low-density lipoproteinMacrophage |
| spellingShingle | Liang Zheng Hongbiao Xu Fufu Zheng Yuanhui Lai Jie Li Weiming Lv Zuojun Hu Wenjian Wang Intervention time decides the status of autophagy, NLRP3 activity and apoptosis in macrophages induced by ox‐LDL Lipids in Health and Disease Atherosclerosis Autophagy Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 Apoptosis; oxidized low-density lipoprotein Macrophage |
| title | Intervention time decides the status of autophagy, NLRP3 activity and apoptosis in macrophages induced by ox‐LDL |
| title_full | Intervention time decides the status of autophagy, NLRP3 activity and apoptosis in macrophages induced by ox‐LDL |
| title_fullStr | Intervention time decides the status of autophagy, NLRP3 activity and apoptosis in macrophages induced by ox‐LDL |
| title_full_unstemmed | Intervention time decides the status of autophagy, NLRP3 activity and apoptosis in macrophages induced by ox‐LDL |
| title_short | Intervention time decides the status of autophagy, NLRP3 activity and apoptosis in macrophages induced by ox‐LDL |
| title_sort | intervention time decides the status of autophagy nlrp3 activity and apoptosis in macrophages induced by ox ldl |
| topic | Atherosclerosis Autophagy Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 Apoptosis; oxidized low-density lipoprotein Macrophage |
| url | https://doi.org/10.1186/s12944-022-01714-x |
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