Macrophage EP4 Deficiency Drives Atherosclerosis Progression via CD36-Mediated Lipid Uptake and M1 Polarization
Atherosclerosis is a chronic inflammatory disease and a major pathological basis of numerous cardiovascular conditions, with a high global mortality rate. Macrophages play a pivotal role in its pathogenesis through phenotypic switching and foam cell formation. Prostaglandin E2 receptor subtype 4 (EP...
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MDPI AG
2025-07-01
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| author | Xinyu Tang Qian Chen Manli Guo Ying Wen Cuiping Jia Yun Bu Ting Wang Yuan Zhang Waiho Tang |
| author_facet | Xinyu Tang Qian Chen Manli Guo Ying Wen Cuiping Jia Yun Bu Ting Wang Yuan Zhang Waiho Tang |
| author_sort | Xinyu Tang |
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| description | Atherosclerosis is a chronic inflammatory disease and a major pathological basis of numerous cardiovascular conditions, with a high global mortality rate. Macrophages play a pivotal role in its pathogenesis through phenotypic switching and foam cell formation. Prostaglandin E2 receptor subtype 4 (EP4) highly expressed on the macrophage surface, is involved in various pathophysiological processes, such as inflammation and lipid metabolism. However, the role of macrophage EP4 in the progression of atherosclerosis remains unclear. To determine whether macrophage EP4 affects the progression of atherosclerosis by regulating foam cell formation and macrophage polarization. Myeloid-specific EP4 knockout mice with an ApoE-deficient background were fed a Western diet for 16 weeks. Our results showed that EP4 expression was significantly downregulated during atherosclerosis. EP4 deficiency was found to exacerbate atherosclerotic plaque formation and destabilizes plaques. In vitro studies further demonstrated that loss of EP4 in myeloid cells promoted foam cell formation and M1 macrophage polarization. Both transcriptomic and proteomic analysis showed that EP4 may regulate these processes by regulating CD36 expression in macrophage, which was further confirmed by Western blot and qPCR. In summary, deficiency of EP4 receptor in macrophages enhance foam cell formation and M1 polarization by upregulating CD36 expression, thereby accelerating the progression of atherosclerosis. |
| format | Article |
| id | doaj-art-dedb0f8fc5c642359fcbda14c7098b1d |
| institution | DOAJ |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-07-01 |
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| series | Cells |
| spelling | doaj-art-dedb0f8fc5c642359fcbda14c7098b1d2025-08-20T03:16:55ZengMDPI AGCells2073-44092025-07-011413102110.3390/cells14131021Macrophage EP4 Deficiency Drives Atherosclerosis Progression via CD36-Mediated Lipid Uptake and M1 PolarizationXinyu Tang0Qian Chen1Manli Guo2Ying Wen3Cuiping Jia4Yun Bu5Ting Wang6Yuan Zhang7Waiho Tang8School of Medicine, South China University of Technology, Guangzhou 510006, ChinaInstitute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, ChinaInstitute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, ChinaInstitute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, ChinaInstitute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, ChinaInstitute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, ChinaInstitute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, ChinaInstitute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, ChinaSchool of Medicine, South China University of Technology, Guangzhou 510006, ChinaAtherosclerosis is a chronic inflammatory disease and a major pathological basis of numerous cardiovascular conditions, with a high global mortality rate. Macrophages play a pivotal role in its pathogenesis through phenotypic switching and foam cell formation. Prostaglandin E2 receptor subtype 4 (EP4) highly expressed on the macrophage surface, is involved in various pathophysiological processes, such as inflammation and lipid metabolism. However, the role of macrophage EP4 in the progression of atherosclerosis remains unclear. To determine whether macrophage EP4 affects the progression of atherosclerosis by regulating foam cell formation and macrophage polarization. Myeloid-specific EP4 knockout mice with an ApoE-deficient background were fed a Western diet for 16 weeks. Our results showed that EP4 expression was significantly downregulated during atherosclerosis. EP4 deficiency was found to exacerbate atherosclerotic plaque formation and destabilizes plaques. In vitro studies further demonstrated that loss of EP4 in myeloid cells promoted foam cell formation and M1 macrophage polarization. Both transcriptomic and proteomic analysis showed that EP4 may regulate these processes by regulating CD36 expression in macrophage, which was further confirmed by Western blot and qPCR. In summary, deficiency of EP4 receptor in macrophages enhance foam cell formation and M1 polarization by upregulating CD36 expression, thereby accelerating the progression of atherosclerosis.https://www.mdpi.com/2073-4409/14/13/1021EP4macrophage polarizationfoam cellCD36atherosclerosis |
| spellingShingle | Xinyu Tang Qian Chen Manli Guo Ying Wen Cuiping Jia Yun Bu Ting Wang Yuan Zhang Waiho Tang Macrophage EP4 Deficiency Drives Atherosclerosis Progression via CD36-Mediated Lipid Uptake and M1 Polarization Cells EP4 macrophage polarization foam cell CD36 atherosclerosis |
| title | Macrophage EP4 Deficiency Drives Atherosclerosis Progression via CD36-Mediated Lipid Uptake and M1 Polarization |
| title_full | Macrophage EP4 Deficiency Drives Atherosclerosis Progression via CD36-Mediated Lipid Uptake and M1 Polarization |
| title_fullStr | Macrophage EP4 Deficiency Drives Atherosclerosis Progression via CD36-Mediated Lipid Uptake and M1 Polarization |
| title_full_unstemmed | Macrophage EP4 Deficiency Drives Atherosclerosis Progression via CD36-Mediated Lipid Uptake and M1 Polarization |
| title_short | Macrophage EP4 Deficiency Drives Atherosclerosis Progression via CD36-Mediated Lipid Uptake and M1 Polarization |
| title_sort | macrophage ep4 deficiency drives atherosclerosis progression via cd36 mediated lipid uptake and m1 polarization |
| topic | EP4 macrophage polarization foam cell CD36 atherosclerosis |
| url | https://www.mdpi.com/2073-4409/14/13/1021 |
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