<span class="fontstyle0">巨噬细胞NLRP3炎症小体通过15-HETE增加心肌纤维化易感性的机制研究</span> #br#

Engineering ›› 2024, Vol. 42 ›› Issue (11) : 143 -156. DOI: 10.1016/j.eng.2024.05.015

研究论文

巨噬细胞NLRP3炎症小体通过15-HETE增加心肌纤维化易感性的机制研究 #br#

Xu Chen ^a^,^b ,
Zhiyong Du ^c ,
Dongqing Guo ^d ,
Jincheng Guo ^a ,
Qianbin Sun ^a ,
Tiantian Liu ^a ,
Kun Hua ^c ,
Chun Li ^e^,^f^,^* ,
Yong Wang ^a^,^* ,
Wei Wang ^a^,^f^,^*

作者信息 +

Activation of the Macrophage-Associated Inflammasome Exacerbates Myocardial Fibrosis Through the 15-HETE-Mediated Pathway in Acute Myocardial Infarction

Xu Chen ^a^,^b^,^# ,
Zhiyong Du ^c^,^# ,
Dongqing Guo ^d ,
Jincheng Guo ^a ,
Qianbin Sun ^a ,
Tiantian Liu ^a ,
Kun Hua ^c ,
Chun Li ^e^,^f^,^* ,
Yong Wang ^a^,^* ,
Wei Wang ^a^,^f^,^*

Author information +

^aSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China

^bDepartment of Pharmacy, Air Force Medical Center, Air Force Medical University, Beijing 100142, China

^cNational Clinical Research Center for Cardiovascular Diseases, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China

^dSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China

^eModern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China

^fState Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

^aSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China

^bDepartment of Pharmacy, Air Force Medical Center, Air Force Medical University, Beijing 100142, China

^cNational Clinical Research Center for Cardiovascular Diseases, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China

^dSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China

^eModern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China

^fState Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

* E-mail addresses: lichun19850204@163.com (C. Li),

doctor_wangyong@163.com (Y. Wang),

wangwei26960@126.com (W. Wang).

Show less

文章历史 +

Received	Accepted	Published
2024-01-31	2024-05-21
Issue Date
2024-05-21

PDF (14300K)

Abstract

This investigation elucidates the spatiotemporal dynamics of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation following myocardial infarction (MI), a process that has not been fully characterized. We revealed early activation of the NLRP3 inflammasome in mice with MI and characterized its dynamic temporal expression. Notably, the knockout and inhibition of Nlrp3 expression were found to significantly mitigate infarct size and enhance cardiac function. Furthermore, our analysis of the spatial characteristics of inflammasome activation revealed predominant activation in macrophages and subsequent activation in fibroblasts on the third day post-MI. To elucidate the nexus between macrophage-associated NLRP3 inflammasome activation and myocardial fibrosis, we employed targeted metabolomics analyses of inflammatory oxylipins, small interfering RNA (siRNA) interference experiments, and various molecular assays. These findings revealed that macrophage-associated inflammasome activation facilitates the conversion of fibroblasts into myofibroblasts via the 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE)-mediated small mother against decapentaplegic (Smad) pathway. Additionally, both mass spectrometry imaging (MSI) and targeted metabolomics analyses confirmed the significant increase in 15-HETE levels in mice with MI and in patients with MI and acute coronary syndrome (ACS). Our comprehensive dataset suggests that NLRP3 inflammasome activation in MI is characterized by distinct temporal and spatial patterns. These insights mark a significant advancement toward precise MI prevention and treatment strategies, particularly early myocardial fibrosis intervention.

关键词

Key words

Myocardial infarction / Macrophage inflammasome / NOD-like receptor family pyrin domain containing 3 / Myocardial fibrosis

引用本文

引用格式 ▾

Xu Chen,Zhiyong Du,Dongqing Guo,Jincheng Guo,Qianbin Sun,Tiantian Liu,Kun Hua,Chun Li,Yong Wang,Wei Wang. 巨噬细胞NLRP3炎症小体通过15-HETE增加心肌纤维化易感性的机制研究 #br#[J]. 工程（英文）, 2024, 42(11): 143-156 DOI:10.1016/j.eng.2024.05.015