DataVXAdvanced SciencePaper
journal article·2025-05Open access

Macrophage HM13/SPP Enhances Foamy Macrophage Formation and Atherogenesis

Yu Cao, Qirong Xie, Qiang Zheng, Jingping Zhang, Mengyu Yao, Zhongyong Du, Lujun Zhang, Tianyang Hu, Yunli Zhao, Jianlin Du, Yongyong Li, Yuxing Feng, ND Melgiri, Xiaodong Zhao, Rongzhong Huang, Yang Sun

Advanced Science· Volume 12· Issue 18
Publisher pageOpen full text
Source abstract

Abstract

Abstract Aryl Hydrocarbon Receptor‐Interacting Protein (AIP) reduces macrophage cholesterol‐ester accumulation and may prevent atherogenic foamy macrophage formation. Analyzing AIP‐associated regulatory gene networks can aid in identifying key regulatory mechanism(s) underlying foamy macrophage formation. A weighted gene co‐expression network analysis on the Stockholm Atherosclerosis Gene Expression (STAGE) patient cohort identifies AIP as a negative correlate of Histocompatibility Minor 13 (HM13), which encodes the ER‐associated degradation (ERAD) protein Signal Peptide Peptidase (HM13/SPP). The negative correlation between AIP and HM13/SPP on mRNA and protein levels is validated in oxLDL‐stimulated macrophages and human plaque foamy macrophages. Mechanistically, AIP, via its chaperone interaction with Aryl Hydrocarbon Receptor (AHR), inhibits p38‐c‐JUN‐mediated HM13 transactivation, thereby suppressing macrophage lipid accumulation. Myeloid HM13/SPP overexpression enhances oxLDL‐induced foamy macrophage formation in vitro as well as atherogenesis and plaque foamy macrophage load in vivo, while myeloid HM13/SPP knockout produces the opposite effects. Mechanistically, myeloid HM13/SPP enhances oxLDL‐induced foamy macrophage formation in vitro as well as atherogenesis and plaque foamy macrophage load in vivo via promoting ERAD‐mediated proteasomal degradation of the metabolic regulator Heme Oxygenase‐1 (HO‐1). In conclusion, AIP downregulates macrophage HM13/SPP, a driver of oxLDL‐induced lipid loading, foamy macrophage generation, and atherogenesis.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Nuclear Receptors and Signaling · Peroxisome Proliferator-Activated Receptors · Lipoproteins and Cardiovascular Health

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Cardiovascular Surgery the First People’s Hospital of Yunnan Province No. 157, Jinbi Road, Xishan District Kunming Yunnan 650032 China

Center for Translational Research in Clinical Medicine the Affiliated Hospital of Kunming University of Science and Technology No. 68, Wenchang Road, Wuhua District Kunming Yunnan 650093 China

Department of Ultrasound Chongqing Key Laboratory of Ultrasound Molecular Imaging the Second Affiliated Hospital of Chongqing Medical University No. 76, Linjiang Road, Yuzhong District Chongqing 400010 China

Department of Hematopathology the First People's Hospital of Yunnan Province No. 157, Jinbi Road, Xishan District Kunming Yunnan 650032 China

Cell Therapy Engineering Research Center for Cardiovascular Diseases in Yunnan Province Yunnan Key Laboratory of Innovative Application of Traditional Chinese Medicine the First People's Hospital of Yunnan Province No. 157, Jinbi Road, Xishan District Kunming Yunnan 650032 China

Precision Medicine Center the Second Affiliated Hospital of Chongqing Medical University No. 76, Linjiang Road, Yuzhong District Chongqing 400010 China

Department of Cardiology the Second Affiliated Hospital of Chongqing Medical University No. 76, Linjiang Road, Yuzhong District Chongqing 400010 China

Department of Geriatric Medicine the Second Affiliated Hospital of Chongqing Medical University No. 76, Linjiang Road, Yuzhong District Chongqing 400010 China

Department of Rehabilitation and Pain Medicine the Ninth People's Hospital of Chongqing No. 69, Jialing Village, Beibei District Chongqing 400700 China

Impactys Foundation for Biomedical Research 10300 Campus Pointe Drive San Diego CA 92121 USA

References (45)

Show source-provided references
1. 10.1016/j.gheart.2014.01.00810.1016/j.gheart.2014.01.008 ↗
2. 10.1016/j.vph.2018.08.00210.1016/j.vph.2018.08.002 ↗
3. 10.1016/j.cels.2016.02.00210.1016/j.cels.2016.02.002 ↗
4. 10.1371/journal.pgen.100075410.1371/journal.pgen.1000754 ↗
5. 10.15252/embj.20148820810.15252/embj.201488208 ↗
6. 10.1126/science.aad646910.1126/science.aad6469 ↗
7. 10.1016/j.cels.2016.06.01210.1016/j.cels.2016.06.012 ↗
8. 10.1186/1471-2164-10-1310.1186/1471-2164-10-13 ↗
9. 10.1161/CIRCGENETICS.111.96077310.1161/CIRCGENETICS.111.960773 ↗
10. 10.1038/s41591-019-0590-410.1038/s41591-019-0590-4 ↗
11. 10.1007/s00395-023-01023-z10.1007/s00395-023-01023-z ↗
12. 10.1161/CIRCULATIONAHA.113.00501510.1161/CIRCULATIONAHA.113.005015 ↗
13. 10.3389/fcell.2020.58164110.3389/fcell.2020.581641 ↗
14. 10.1038/s41577-019-0125-810.1038/s41577-019-0125-8 ↗
15. 10.1016/j.bcp.2008.08.03110.1016/j.bcp.2008.08.031 ↗
16. 10.1034/j.1600-0463.2002.100604.x10.1034/j.1600-0463.2002.100604.x ↗
17. 10.1074/jbc.M10020920010.1074/jbc.M100209200 ↗
18. Köffel R. · Blood The J. Am. Soci. Hematol. · 2014 · 124 · 2713
19. 10.1210/jc.2006-251310.1210/jc.2006-2513 ↗
20. 10.1530/ERC-16-004110.1530/ERC-16-0041 ↗
21. 10.1016/j.bcp.2018.03.01510.1016/j.bcp.2018.03.015 ↗
22. 10.1172/jci.insight.13844310.1172/jci.insight.138443 ↗
23. 10.1002/cyto.a.2201210.1002/cyto.a.22012 ↗
24. 10.1016/j.tcb.2020.09.00610.1016/j.tcb.2020.09.006 ↗
25. 10.1161/CIRCRESAHA.114.30293710.1161/CIRCRESAHA.114.302937 ↗
26. 10.1093/cvr/cvw19410.1093/cvr/cvw194 ↗
27. 10.1083/jcb.20131200910.1083/jcb.201312009 ↗
28. 10.1073/pnas.96.18.1040310.1073/pnas.96.18.10403 ↗
29. 10.1083/jcb.20090611010.1083/jcb.200906110 ↗
30. 10.1161/CIRCRESAHA.107.15172010.1161/CIRCRESAHA.107.151720 ↗
31. 10.1111/pin.1320210.1111/pin.13202 ↗
32. 10.1016/j.bbamcr.2016.04.00110.1016/j.bbamcr.2016.04.001 ↗
33. 10.1016/j.jacc.2019.03.01010.1016/j.jacc.2019.03.010 ↗
34. 10.1038/nrcardio.2017.3410.1038/nrcardio.2017.34 ↗
35. 10.1016/j.imlet.2020.10.00310.1016/j.imlet.2020.10.003 ↗
36. 10.1385/CT:4:4:36310.1385/CT:4:4:363 ↗
37. 10.1007/s00109-017-1575-810.1007/s00109-017-1575-8 ↗
38. 10.1016/j.jbc.2024.10564410.1016/j.jbc.2024.105644 ↗
39. 10.1161/CIRCULATIONAHA.108.80861810.1161/CIRCULATIONAHA.108.808618 ↗
40. 10.1126/sciadv.aax918310.1126/sciadv.aax9183 ↗
41. Venegas‐Pino D. E. · JoVE (J. Visual. Exp.) · 2013 · 5
42. 10.1073/pnas.173249410010.1073/pnas.1732494100 ↗
43. 10.1007/s00395-011-0192-x10.1007/s00395-011-0192-x ↗
44. 10.1016/j.celrep.2020.10799010.1016/j.celrep.2020.107990 ↗
45. 10.1093/eurheartj/ehab66010.1093/eurheartj/ehab660 ↗