| Autor: |
Ryuta Sugihara, Manabu Taneike, Tomokazu Murakawa, Takahito Tamai, Hiromichi Ueda, Rika Kitazume-Taneike, Takafumi Oka, Yasuhiro Akazawa, Hiroki Nishida, Kentaro Mine, Ayana Hioki, Jumpei Omi, Shigemiki Omiya, Junken Aoki, Kazutaka Ikeda, Kazuhiko Nishida, Makoto Arita, Osamu Yamaguchi, Yasushi Sakata, Kinya Otsu |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 14, Iss 1, Pp 1-12 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-023-40201-4 |
| Popis: |
Abstract Heart failure is a leading cause of mortality in developed countries. Cell death is a key player in the development of heart failure. Calcium-independent phospholipase A2β (iPLA2β) produces lipid mediators by catalyzing lipids and induces nuclear shrinkage in caspase-independent cell death. Here, we show that lysophosphatidylserine generated by iPLA2β induces necrotic cardiomyocyte death, as well as contractile dysfunction mediated through its receptor, G protein-coupled receptor 34 (GPR34). Cardiomyocyte-specific iPLA2β-deficient male mice were subjected to pressure overload. While control mice showed left ventricular systolic dysfunction with necrotic cardiomyocyte death, iPLA2β-deficient mice preserved cardiac function. Lipidomic analysis revealed a reduction of 18:0 lysophosphatidylserine in iPLA2β-deficient hearts. Knockdown of Gpr34 attenuated 18:0 lysophosphatidylserine-induced necrosis in neonatal male rat cardiomyocytes, while the ablation of Gpr34 in male mice reduced the development of pressure overload-induced cardiac remodeling. Thus, the iPLA2β—lysophosphatidylserine—GPR34—necrosis signaling axis plays a detrimental role in the heart in response to pressure overload. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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