郑乐民教授团队与其合作单位完成的“国人心血管相关疾病的代谢特征和发病机制的探索与引用”荣获2022年北京医学科技奖一等奖。“北京医学科技奖”是由北京医学会设立的首都医药卫生行业的科技奖项,旨在引领首都医学科技创新发展,推动尖端医学科研成果的产出。
该团队从临床出发,通过生物质谱、生物信息学及病历资料进行多方位探索,首次发现了琥珀酸在心血管疾病中的致病新理论;率先通过非靶向代谢组学技术发现新肠道菌群代谢物质三甲基五氨基戊酸(TMAVA)通过干预脂肪酸氧化加剧心衰与非酒精性脂肪肝,发现肠道菌群活性代谢产物在心血管疾病中的重要作用及关键机制;首次利用CRISPR/Cas9构建拟人化基因敲除仓鼠模型,为心血管疾病的转化医学研究搭建理想平台,获得多项专利并发现ApoC3这个新的治疗糖尿病肾病的潜在靶点;引入纳米材料技术实现荧光/超声结合检测,为血管斑块临床诊断与治疗提供了新手段。
郑乐民
Email: zhengl@bjmu.edu.cn
研究员、博士生导师
心血管病理生理学
北京大学心血管研究所副所长,全国重点实验室主任助理,北京大学基础医学院党委委员,基础医学院心脑血管和代谢学科群副主任。国家“万人计划”科技创新领军人才(万人);国家“优秀青年基金”获得者(优青2014);国家“万人计划”青年拔尖人才(青拔2015)。作为第一完成人获得2022年北京医学科技奖一等奖和2022年度北京市科学技术奖二等奖。主持国自然血管重大等7项国自然基金等,作为项目负责人(2023)参加科技部重大专项等5项,主持北京市重点基金(2023)等3项与京津冀联合基金(2023)。
共发表SCI文章126篇,其中94篇SCI责任作者,SCI引用超5300次(h-index 37)。主要作者文章(通讯作者含共同通讯, 其中IF大于等于10分为24篇;IF大于等于20分为6篇)
实验室网站:www.leminlab.com
实验室研究领域
1.代谢以及肠道菌群代谢对心脑血管疾病影响研究:
代谢与心脑血管疾病研究密切相关,心脑血管疾病(包括心梗与中风)的发生发展与预后都有代谢的参与,代谢调控是基因与蛋白调控之后一个重要的研究领域。郑乐民团队先后发现了一些代谢分子以及相关蛋白对心脑血管疾病的新的病理生理机制与临床相关研究,其中包括琥珀酸代谢、能量代谢、脂代谢与脂蛋白等信号通路对于心脑血管系统的影响。
肠道菌群是人体代谢的另一个重要来源,它存在着稳态与非稳态的平衡,这些平衡的打破能够带来不同的代谢物,由于这些代谢物的存在,从而影响到了肠道之外的其他器官,比如心脑血管系统等,从而产生了肠-心轴、肠-脑轴、肠-肝轴等新的理论体系。郑团队已发现了一系列新的肠道菌群代谢物例如TMAVA(三甲基-5-氨基戊酸)对心脏以及肝脏的病理生理作用,也发现了已经被大家熟知的TMAO(氧化三甲胺)新的病理生理功能比如在卒中与肺动脉高压中的新机制。
2. 代谢对其他相关疾病影响研究:
代谢除了对心脑血管疾病产生巨大作用外,代谢性疾病也会影响到心脑血管疾病之外的疾病,例如糖尿病。同时代谢方面的机制不但能影响到糖尿病肾病、脂肪肝等代谢性疾病,还能通过代谢通路影响到肿瘤中的血管新生以及肿瘤。
3. 结合新材料新技术开展心脑血管相关转化医学研究:
结合纳米技术与探针材料开展对心脑血管的诊断与治疗研究,对特定细胞例如炎症细胞等进行标记,对特定细胞进行药物运输,使得心脑血管的诊断与治疗能够在新赛道上继续发展。开展包括生物质谱技术在内的诊断学研究,将新的监测与诊断技术应用在心脑血管疾病的预防与预后上。
近三年实验室代表文章(*作为责任作者):
1. Rui Zhan#, Xia Meng#, Dongping Tian, Jie Xu, Hongtu Cui, Jialei Yang, Yangkai Xu, Mingming Shi, Jing Xue, Weiwei Yu, Gaofei Hu, Ke Li, Xiaoxiao Ge, Qi Zhang, Mingming Zhao, Jianyong Du, Xin Guo, Wenli Xu, Yang Gao, Changyu Yao, Fan Chen, Yue Chen, Wenxin Shan, Yujie Zhu, Liang Ji, Bing Pan, Yan Yu, Wenguang Li, Xuyang Zhao, Qihua He, Xiaohui Liu, Yue Huang, Shengyou Liao, Bin Zhou, Dehua Chui, Y Eugene Chen, Zheng Sun, *Erdan Dong, *Yongjun Wang, *Lemin Zheng. NAD+ rescues aging-induced blood-brain barrier damage via the CX43-PARP1 axis. Neuron. 2023 Aug 29:S0896-6273(23)00622-0. (IF=16.2,JCR:Q1)
2. Pengxiang Qu#, Oren Rom#, Ke Li#, Linying Jia, Xiaojing Gao, Zhipeng Liu, Shusi Ding, Mingming Zhao, Huiqing Wang, Shuangshuang Chen, Xuelian Xiong, Ying Zhao, Chao Xue, Yang Zhao, Chengshuang Chu, Bo Wen, Alexandra C. Finney, Zuowen Zheng, Wenbin Cao, Jinpeng Zhao, Liang Bai, Sihai Zhao, Duxin Sun, Rong Zeng, Jiandie Lin, Wanqing Liu, *Lemin Zheng, *Jifeng Zhang, *Enqi Liu, Y. *Eugene Chen. DT-109 ameliorates nonalcoholic steatohepatitis in nonhuman primates. Cell Metabolism. 2023, April 10, ISSN 1550-4131. (IF=29,JCR:Q1)
3. Zekun Wang#, Nana Yang#, Yajun Hou, Yuqing Li, Chenyang Yin, Endong Yang, Huanhuan Cao, Gaofei Hu, Jing Xue, Jialei Yang, Ziyu Liao, Weiyun Wang, *Dongdong Sun, *Cundong Fan, *Lemin Zheng. L-Arginine-Loaded Gold Nanocages Ameliorate Myocardial Ischemia/Reperfusion Injury by Promoting Nitric Oxide Production and Maintaining Mitochondrial Function. Advanced science (Weinh). 2023 Sep;10(26):e2302123. (IF=15.1,JCR:Q1)
4. Jianing Gao#, Huanhuan Cao, Gaofei Hu, Yufei Wu, Yangkai Xu, Hongtu Cui, Hong S Lu, *Lemin Zheng. The mechanism and therapy of aortic aneurysms. Signal transduction and targeted therapy. 2023 Feb 3;8(1):55. (IF=39.3,JCR:Q1)
5. Qingyuan Liu#, Ke Li#, Hongwei He, Zengli Miao, Hongtu Cui, Jun Wu, Shusi Ding, Zheng Wen, Jiyuan Chen, *Xiaojie Lu, *Jiangan Li, *Lemin Zheng, *Shuo Wang. The markers and risk stratification model of intracranial aneurysm instability in a large Chinese cohort. Science bulletin. 2023 May 10:S2095-9273(23)00308-0. (IF=18.9,JCR:Q1)
6. Jianing Gao#, Yanghui Chen#, Huiqing Wang, Xin Li, Ke Li, Yangkai Xu, Xianwei Xie, Yansong Guo, Nana Yang, Xinhua Zhang, Dong Ma, Hong S Lu, Ying H Shen, Yong Liu, Jifeng Zhang, Y Eugene Chen, Alan Daugherty, *Dao Wen Wang, *Lemin Zheng. Gasdermin D Deficiency in Vascular Smooth Muscle Cells Ameliorates Abdominal Aortic Aneurysm Through Reducing Putrescine Synthesis. Advanced Science (Weinh). 2022 Dec 25:e2204038. (IF=15.1,JCR:Q1)
7. Huanhuan Cao, Yujie Zhu, Gaofei Hu, Qi Zhang, *Lemin Zheng. Gut microbiome and metabolites, the future direction of diagnosis and treatment of atherosclerosis? Pharmacological Research. 2023 Jan;187:106586. (IF=9.3,JCR:Q1)
8. Mingming Zhao#, Haoran Wei#, Chenze Li, Rui Zhan, Changjie Liu, Jianing Gao, Yaodong Yi, Xiao Cui, Wenxin Shan, Liang Ji, Bing Pan, Si Cheng, Moshi Song, Haipeng Sun, Huidi Jiang, Jun Cai, Minerva Garcia-Barrio, Y. Eugene Chen, Xiangbao Meng, Erdan Dong, *Dao Wen Wang, *Lemin Zheng. Gut microbiota production of trimethyl-5-aminovaleric acid reduces fatty acid oxidation and accelerates cardiac hypertrophy. Nature Communications. 2022 Apr 1;13(1):1757. (IF=16.6,JCR:Q1)
9. Yang Y#, Zeng Q#, Gao J#, Yang B, Zhou J, Li K, Li L, Wang A, Li X, Liu Z, Luo Q, Zhao Z, Liu B, Xue J, Jiang X, Konerman MC, *Zheng Lemin, *Xiong C. High-circulating gut microbiota-dependent metabolite trimethylamine N-oxide is associated with poor prognosis in pulmonary arterial hypertension. European Heart Journal Open. 2022 Mar 29;2(5):oeac021.
10. Xu J#, Hao X#, Zhan R#, Jiang X, Jin A, Xue J, Cheng A, Liu J, Lin J, Meng X, Li H, *Zheng L, *Wang Y. Effect of Lipoprotein(a) on Stroke Recurrence Attenuates at Low LDL-C (Low-Density Lipoprotein) and Inflammation Levels. Stroke. 2022 Apr 12:101161STROKEAHA121034924. (JCR:Q1)
11. Xiao-Xiao Chen#, Yufei Wu#, Xiaoxiao Ge, Liandi Lei, *Li-Ya Niu, *Qing-Zheng Yang, *Lemin Zheng. In vivo imaging of heart failure with preserved ejection fraction by simultaneous monitoring of cardiac nitric oxide and glutathione using a three-channel fluorescent probe. Biosensors and Bioelectronics. Volume 214, 2022, 114510, ISSN 0956-5663.(IF=12.6,JCR:Q1)
12. Cui H#, Chen Y#, Li K, Zhan R, Zhao M, Xu Y, Lin Z, Fu Y, He Q, Tang PC, Lei I, Zhang J, Li C, Sun Y, Zhang X, Horng T, Lu HS, Chen YE, Daugherty A, *Wang D, *Lemin Zheng. Untargeted metabolomics identifies succinate as a biomarker and therapeutic target in aortic aneurysm and dissection. European Heart Journal. 2021 Nov 7;42(42):4373-4385. (IF=39.3,JCR:Q1)
13. Jiang X, Xu J, Hao X, Xue J, Li K, Jin A, Lin J, Meng X, *Zheng L, *Wang Y. Elevated lipoprotein(a) and lipoprotein-associated phospholipase A2 are associated with unfavorable functional outcomes in patients with ischemic stroke. Journal of Neuroinflammation. 2021 Dec 28;18(1):307. (IF=9.3,JCR:Q1)
14. Xu J#, Zhao M#, Wang A, Xue J, Cheng S, Cheng A, Gao J, Zhang Q, Zhan R, Meng X, Xu M, Li H, Zheng L*, Wang Y*. Association Between Plasma Trimethyllysine and Prognosis of Patients With Ischemic Stroke. Journal of the American Heart Association. 2021 Dec 7;10(23):e020979.
15. Xu J#, Cheng A#, Song B, Zhao M, Xue J, Wang A, Dai L, Jing J, Meng X, Li H, *Zheng L, *Wang Y. Trimethylamine N-Oxide and Stroke Recurrence Depends on Ischemic Stroke Subtypes. Stroke. 2021 Nov 19:STROKEAHA120031443. (JCR:Q1)
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