2023 Fiscal Year Final Research Report
The role of caspase-11-dependent pyroptosis in atherosclerotic lesion
| Project/Area Number |
21K06875
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49010:Pathological biochemistry-related
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
高橋 将文 自治医科大学, 医学部, 教授 (40296108)
相澤 恵美 自治医科大学, 医学部, 助教 (80877621)
駒田 敬則 自治医科大学, 医学部, 講師 (90824730)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 炎症 / パイロトーシス / 動脈硬化 |
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| Outline of Final Research Achievements |
Caspase-11 is an inflammatory caspase that triggers pyroptosis. However, the effect of caspase-11 deficiency on the development of atherosclerosis has not been fully evaluated. In the present study, we investigated the role of caspase-11 in the development of atherosclerosis. Apoe-deficient mice carrying caspase-11 mutation were fed a Western diet for 8 weeks. The formation of the necrotic core and deposition of cholesterol crystals are prevented by caspase-11 deficiency. The neutrophil infiltration into atherosclerotic lesions was also attenuated by caspase-11 deficiency. RNA-seq analysis revealed that upregulations of caspase-11 and neutrophil migration are common features of advanced atherosclerotic lesions. Furthermore, similar expression profiles were observed in unstable human plaque. These data suggest that caspase-11 regulates neutrophil recruitment and plaque destabilization in advanced atherosclerotic lesions.
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| Free Research Field |
代謝学
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| Academic Significance and Societal Importance of the Research Achievements |
心血管イベントの抑制には血中LDLコレステロールの低下だけでは不十分であることが明らかになってきており，この残余リスクを制御する標的として動脈硬化病変における炎症が注目されている．本研究成果は進展した動脈硬化病変においてカスパーゼ11が好中球の浸潤を制御することを明らかにした．炎症性カスパーゼが引き起こすパイロトーシスとそれに伴う好中球の浸潤は，今後，動脈硬化における炎症を制御し，心血管イベントを抑制する上での有効な標的として期待される．
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