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9. Flavin Containing Monooxygenase 2 Prevents Cardiac Fibrosis via CYP2J3-SMURF2 Axis.

Author

Ni, Cheng, Chen, Yongjian, Xu, Yinchuan, Zhao, Jing, Li, Qingju, Xiao, Changchen, Wu, Yan, Wang, Jingyi, Wang, Yingchao, Zhong, Zhiwei, Zhang, Ling, Wu, Rongrong, Liu, Qingnian, Wu, Xianpeng, Ke, Changle, Zhu, Wei, Chen, Jinghai, Huang, Jijun, Wang, Yibin, Wang, Jianan, and Hu, Xinyang

Subjects
cytosol, downregulation, fibrosis, humans, myocardial infarction
Abstract

BACKGROUND: Cardiac fibrosis is a common pathological feature associated with adverse clinical outcome in postinjury remodeling and has no effective therapy. Using an unbiased transcriptome analysis, we identified FMO2 (flavin-containing monooxygenase 2) as a top-ranked gene dynamically expressed following myocardial infarction (MI) in hearts across different species including rodents, nonhuman primates, and human. However, the functional role of FMO2 in cardiac remodeling is largely unknown. METHODS: Single-nuclei transcriptome analysis was performed to identify FMO2 after MI; FMO2 ablation rats were generated both in genetic level using the CRISPR-cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) technology and lentivirus-mediated manner. Gain-of-function experiments were conducted using postn-promoter FMO2, miR1a/miR133a-FMO2 lentivirus, and enzymatic activity mutant FMO2 lentivirus after MI. RESULTS: A significant downregulation of FMO2 was consistently observed in hearts after MI in rodents, nonhuman primates, and patients. Single-nuclei transcriptome analysis showed cardiac expression of FMO2 was enriched in fibroblasts rather than myocytes. Elevated spontaneous tissue fibrosis was observed in the FMO2-null animals without external stress. In contrast, fibroblast-specific expression of FMO2 markedly reduced cardiac fibrosis following MI in rodents and nonhuman primates associated with diminished SMAD2/3 phosphorylation. Unexpectedly, the FMO2-mediated regulation in fibrosis and SMAD2/3 signaling was independent of its enzymatic activity. Rather, FMO2 was detected to interact with CYP2J3 (cytochrome p450 superfamily 2J3). Binding of FMO2 to CYP2J3 disrupted CYP2J3 interaction with SMURF2 (SMAD-specific E3 ubiquitin ligase 2) in cytosol, leading to increased cytoplasm to nuclear translocation of SMURF2 and consequent inhibition of SMAD2/3 signaling. CONCLUSIONS: Loss of FMO2 is a conserved molecular signature in postinjury hearts. FMO2 possesses a previously uncharacterized enzyme-independent antifibrosis activity via the CYP2J3-SMURF2 axis. Restoring FMO2 expression exerts potent ameliorative effect against fibrotic remodeling in postinjury hearts from rodents to nonhuman primates. Therefore, FMO2 is a potential therapeutic target for treating cardiac fibrosis following injury.

Published
2022

37. Construction Path of Smart Health Care Platform for the Elderly in China

Author

Hou Hanpo, Wei He, Wang Yingchao, Yu Jin, and Qiu Guixing

Subjects
Ageing, Healthy China, home-based community care for the elderly, smart health care for the elderly, ervice for the aged, health care platform for the elderly, Engineering (General). Civil engineering (General), TA1-2040
Abstract

China has a large elderly population and its aging speed is accelerating, which pose a significant challenge for the country to cope with problems induced by population ageing. To address this, it is necessary to establish a smart health care platform for the elderly in China using modern technologies. In this paper, we analyze the construction background, concept, and development status of smart health care platforms for the elderly in China. Using the smart health care platform established in Xihu District of Hangzhou City as a case, we analyze the construction model and challenges of the platform and summarize the common features of the platforms in China. Moreover, we propose an implementation path for platform development in China. The platform should be built to contribute to the establishment of a Healthy China using scientific and technological means and based on the interconnection of national health care information and data; service resources need to be mobilized to provide a community-based comprehensive service; remote health data monitoring and health management are required to strengthen information support; and geographical advantages need to be maximized to promote local elderly health care industries. Furthermore, we suggest that China should accelerate the construction of its health care industry as well as the transformation of scientific and technological achievements, improve the health assessment system for guaranteeing the physical and mental health of the elderly, accelerate the construction of the relevant standards system, and coordinate urban–rural development in this industry.

Published
2022
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