Seipin‐Mediated Lipid Droplet Formation in Cardiomyocytes Ameliorates Cardiac Ischemia/Reperfusion Injury
Source abstract
Abstract
Abstract Cardiac ischemia/reperfusion (I/R) injury is an important therapeutic target for ischemic heart disease. Lipid droplets (LDs) are the key organelles involved in lipid metabolism. This study aimed to identify the LD‐mediated protection against lipotoxicity in cardiac I/R injury. LD accumulation is upregulated in hearts subjected to I/R injury; however, it is insufficient to neutralize lipotoxicity or prevent cardiomyocyte death. Seipin played a central role in LD biogenesis in cardiomyocytes following I/R injury. Seipin deficiency led to reduced LD levels and exacerbated cardiac I/R injury. Whereas increased LD levels, via Seipin overexpression or lipolysis inhibition, ameliorated myocardial I/R injury. I/R‐induced downregulation of Seipin is attributed to the reduced expression of its transcription factor USF1, which is required for metabolic adaptation in acute myocardial ischemia. These findings not only elucidate the pathophysiological roles of LDs and Seipin but also provide a promising therapeutic target for myocardial I/R injury.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Lipid metabolism and biosynthesis · Plant Surface Properties and Treatments · Biodiesel Production and Applications
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Institute of Cardiovascular Sciences State Key Laboratory of Vascular Homeostasis and Remodeling School of Basic Medical Sciences Peking University Health Science Center Beijing 100191 China
Department of Cardiology and Institute of Vascular Medicine Peking University Third Hospital Beijing 100191 China
Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases Haihe Laboratory of Cell Ecosystem Chinese Academy of Medical Sciences Beijing 100191 China
Department of Cardiology Beijing Anzhen Hospital Capital Medical University Beijing 100029 China
State Key Laboratory of Membrane Biology Institute of Molecular Medicine College of Future Technology Peking University Beijing 100871 China
NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides Beijing Key Laboratory of Cardiovascular Receptors Research Peking University Beijing 100191 China
Institute of Cardiovascular Diseases The First Affiliated Hospital of Dalian Medical University Dalian 116021 China
Funding
National Key Research and Development Program of China · National Natural Science Foundation of China · Natural Science Foundation of Beijing Municipality · China Postdoctoral Science Foundation
References (98)
Show source-provided references
1. GBD 2021 Causes of Death Collaborators Lancet2024 403 2100.
2. GBD 2019 Diseases and Injuries Collaborators Lancet2020 396 1204.
3. 10.1093/eurheartj/ehaa110910.1093/eurheartj/ehaa1109 ↗
4. 10.1056/NEJMoa220660610.1056/NEJMoa2206606 ↗
5. 10.1038/nrcardio.2015.16510.1038/nrcardio.2015.165 ↗
6. Heusch G. · Eur. Heart J. · 2017 · 38 · 774
7. 10.1016/j.jacc.2024.02.05610.1016/j.jacc.2024.02.056 ↗
8. 10.1016/j.tem.2023.10.01010.1016/j.tem.2023.10.010 ↗
9. 10.1161/CIRCULATIONAHA.120.04995210.1161/CIRCULATIONAHA.120.049952 ↗
10. 10.1126/science.abm163810.1126/science.abm1638 ↗
11. 10.1038/nrm361910.1038/nrm3619 ↗
12. 10.1161/CIRCULATIONAHA.121.05584110.1161/CIRCULATIONAHA.121.055841 ↗
13. 10.1038/nm.250710.1038/nm.2507 ↗
14. 10.1161/CIRCRESAHA.121.31824110.1161/CIRCRESAHA.121.318241 ↗
15. 10.1038/s41569-018-0044-610.1038/s41569-018-0044-6 ↗
16. 10.1093/cvr/cvad10010.1093/cvr/cvad100 ↗
17. 10.1016/j.cmet.2012.04.00610.1016/j.cmet.2012.04.006 ↗
18. 10.1016/j.cmet.2015.12.00910.1016/j.cmet.2015.12.009 ↗
19. 10.1038/nrcardio.2017.10210.1038/nrcardio.2017.102 ↗
20. 10.1016/j.biopha.2023.11482710.1016/j.biopha.2023.114827 ↗
21. 10.1002/cbin.1211410.1002/cbin.12114 ↗
22. 10.1161/CIRCRESAHA.119.31489810.1161/CIRCRESAHA.119.314898 ↗
23. 10.1161/CIRCRESAHA.118.31137110.1161/CIRCRESAHA.118.311371 ↗
24. 10.1152/physrev.00030.202010.1152/physrev.00030.2020 ↗
25. 10.1161/CIRCULATIONAHA.115.01935110.1161/CIRCULATIONAHA.115.019351 ↗
26. 10.1126/scitranslmed.aao030310.1126/scitranslmed.aao0303 ↗
27. 10.2337/db14-194310.2337/db14-1943 ↗
28. 10.1146/annurev-arplant-070122-02175210.1146/annurev-arplant-070122-021752 ↗
29. 10.1038/s41580-018-0085-z10.1038/s41580-018-0085-z ↗
30. 10.1038/s41574-023-00845-010.1038/s41574-023-00845-0 ↗
31. 10.1146/annurev-cellbio-100616-06060810.1146/annurev-cellbio-100616-060608 ↗
32. 10.1002/advs.20230990710.1002/advs.202309907 ↗
33. 10.1007/s00395-012-0323-z10.1007/s00395-012-0323-z ↗
34. 10.1113/jphysiol.2008.16331110.1113/jphysiol.2008.163311 ↗
35. 10.1002/ctm2.90210.1002/ctm2.902 ↗
36. 10.1161/CIRCRESAHA.121.31947810.1161/CIRCRESAHA.121.319478 ↗
37. 10.1161/CIRCULATIONAHA.121.05592010.1161/CIRCULATIONAHA.121.055920 ↗
38. 10.1159/00052012210.1159/000520122 ↗
39. 10.1016/j.devcel.2022.01.00310.1016/j.devcel.2022.01.003 ↗
40. 10.1016/j.molcel.2020.01.01410.1016/j.molcel.2020.01.014 ↗
41. 10.1038/s41556-022-00974-010.1038/s41556-022-00974-0 ↗
42. 10.1016/j.cell.2018.05.04710.1016/j.cell.2018.05.047 ↗
43. 10.1016/j.tcb.2021.06.00310.1016/j.tcb.2021.06.003 ↗
44. 10.3390/biom1206084010.3390/biom12060840 ↗
45. 10.1093/hmg/ddr20510.1093/hmg/ddr205 ↗
46. 10.1096/fj.201701427R10.1096/fj.201701427R ↗
47. 10.1016/j.jacbts.2019.07.00810.1016/j.jacbts.2019.07.008 ↗
48. 10.1002/advs.20240635910.1002/advs.202406359 ↗
49. 10.1016/j.jhep.2017.11.01410.1016/j.jhep.2017.11.014 ↗
50. 10.1016/j.apsb.2021.09.01910.1016/j.apsb.2021.09.019 ↗
51. 10.1016/j.xcrm.2020.10000110.1016/j.xcrm.2020.100001 ↗
52. 10.1172/jci.insight.12978110.1172/jci.insight.129781 ↗
53. 10.1002/ctm2.73610.1002/ctm2.736 ↗
54. 10.1093/nar/gkx24710.1093/nar/gkx247 ↗
55. 10.1038/s42255-023-00786-y10.1038/s42255-023-00786-y ↗
56. 10.1016/j.molmed.2004.06.01110.1016/j.molmed.2004.06.011 ↗
57. 10.1038/s41574-021-00471-810.1038/s41574-021-00471-8 ↗
58. 10.1038/nature1060210.1038/nature10602 ↗
59. 10.1016/j.apsb.2020.03.00410.1016/j.apsb.2020.03.004 ↗
60. 10.1016/j.bbrc.2016.08.01510.1016/j.bbrc.2016.08.015 ↗
61. 10.1126/scitranslmed.aad001510.1126/scitranslmed.aad0015 ↗
62. 10.1038/ni.282310.1038/ni.2823 ↗
63. 10.1038/s41419-019-1516-210.1038/s41419-019-1516-2 ↗
64. 10.3390/ijms2206279810.3390/ijms22062798 ↗
65. 10.1161/CIRCULATIONAHA.114.01371010.1161/CIRCULATIONAHA.114.013710 ↗
66. 10.1038/ncomms1399710.1038/ncomms13997 ↗
67. 10.1016/j.tcb.2021.01.00410.1016/j.tcb.2021.01.004 ↗
68. 10.1002/advs.20240167610.1002/advs.202401676 ↗
69. 10.1038/s41586-024-07185-710.1038/s41586-024-07185-7 ↗
70. 10.1038/s41581-023-00741-w10.1038/s41581-023-00741-w ↗
71. 10.1038/s41418-023-01241-x10.1038/s41418-023-01241-x ↗
72. 10.1038/s12276-023-00958-610.1038/s12276-023-00958-6 ↗
73. 10.1038/s41556-023-01162-410.1038/s41556-023-01162-4 ↗
74. 10.1172/JCI4090510.1172/JCI40905 ↗
75. 10.1161/CIRCULATIONAHA.124.07219410.1161/CIRCULATIONAHA.124.072194 ↗
76. 10.1016/j.plipres.2019.10098910.1016/j.plipres.2019.100989 ↗
77. 10.1007/s10753-023-01844-z10.1007/s10753-023-01844-z ↗
78. 10.1177/107424842097111310.1177/1074248420971113 ↗
79. 10.1016/j.freeradbiomed.2019.07.00610.1016/j.freeradbiomed.2019.07.006 ↗
80. Kolleritsch S. · Cardiovasc. Res. · 2020 · 116 · 339
81. 10.1016/j.bbalip.2020.15887310.1016/j.bbalip.2020.158873 ↗
82. 10.1038/s42255-019-0138-410.1038/s42255-019-0138-4 ↗
83. 10.1038/nature1390910.1038/nature13909 ↗
84. 10.1016/j.ymben.2023.02.00210.1016/j.ymben.2023.02.002 ↗
85. 10.1038/s41589-018-0132-210.1038/s41589-018-0132-2 ↗
86. 10.1016/j.jhep.2023.10.04210.1016/j.jhep.2023.10.042 ↗
87. 10.1016/j.celrep.2016.10.03710.1016/j.celrep.2016.10.037 ↗
88. 10.1194/jlr.M01756610.1194/jlr.M017566 ↗
89. 10.1016/j.jlr.2022.10030910.1016/j.jlr.2022.100309 ↗
90. 10.1073/pnas.132402511110.1073/pnas.1324025111 ↗
91. 10.3390/ijms2302074010.3390/ijms23020740 ↗
92. 10.2337/db16-073310.2337/db16-0733 ↗
93. 10.1016/j.mce.2019.03.00510.1016/j.mce.2019.03.005 ↗
94. 10.1002/brb3.319510.1002/brb3.3195 ↗
95. 10.1080/15548627.2021.188683910.1080/15548627.2021.1886839 ↗
96. 10.1016/j.celrep.2021.11021310.1016/j.celrep.2021.110213 ↗
97. 10.1016/j.cmet.2014.03.02810.1016/j.cmet.2014.03.028 ↗
98. 10.15252/embj.20179757210.15252/embj.201797572 ↗