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Mechanistic perspectives of calorie restriction on vascular homeostasis

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Science China(Life Sciences) 2014年第8期57卷 742-754页

作者： LIU Yue chen houzao LIU DePei State Key Laboratory of Medical Molecular Biology Department of Biochemistry and Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences & Peking Union Medical College

Calorie restriction(CR)is a dietary regime based on low calorie *** without malnutrition extends lifespan in a wide range of organisms from yeast to rodents,and CR can prevent and delay the onset of age-related functional decline and diseases in human and non-human *** is a safe and effective intervention to reduce vascular risk factors in *** recent years,studies in rodents have provided mechanistic insights into the beneficial effects of CR on vascular homeostasis,including reduced oxidative stress,enhanced nitric oxide(NO)bioactivity,and decreased inflammation.A number of important molecules,including sirtuins,AMP-activated protein kinase,mammalian targets of rapamycin,endothelial nitric oxidase and their regulatory pathways are involved in the maintenance of vascular *** has shown that these pathways are responsible for many aspects of CR’s effects,and that they may also mediate the effects of CR on vasculature.

关键词： calorie restriction(CR) vascular homeostasis Sirtuin 1(SIRT1) AMP-activated protein kinase(AMPK) mammalian target of rapamycin(mTOR) endothelial nitric oxide synthase(eNOS)

Translational research:Lessons from past research,growing up nowadays,and development goal in future

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Science China(Life Sciences) 2011年第12期54卷 1085-1088页

作者： ZHANG ZhuQin chen houzao LIU DePei National Laboratory of Medical Molecular Biology Institute of Basic Medical Science Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100005 China

Recently, with coming of the ＂omics＂ era and rapid devel- opment of basic research in biology and medicine, huge information about biology and life has been achieved. However, many research results cannot be translated into clinical practice. Under this circumstance, the concept of ＂translational research＂ is raised [1-4] and widely spread. ＂Translational research＂ is patient-oriented research which connects basic medicine and clinical medicine [2].

关键词：翻译临床医学基础研究临床实践研究成果基础医学生物学

Baicalein protects against the development of angiotensin II-induced abdominal aortic aneurysms by blocking JNK and p38 MAPK signaling

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Science China(Life Sciences) 2016年第9期59卷 940-949页

作者： Fang Wang houzao chen Yunfei Yan Yue Liu Shuyang Zhang Depei Liu State Key Laboratory of Medical Molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & Peking Union Medical College Department of Cardiology Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College

An abdominal aortic aneurysm(AAA) is a permanent, localized dilatation of the abdominal aorta. In western countries, the morbidity of AAA is approximately 8%. Currently, pharmacotherapies for AAA are limited. Here, we demonstrate that baicalein(BAI), the main component of the Chinese traditional drug "Huang Qin", attenuates the incidence and severity of AAA in Apoe儃/儃 mice infused with angiotensin II(AngII). Mechanically, BAI treatment decreases AngII-induced reactive oxygen species(ROS) production in the aortic wall. Moreover, BAI inhibits inflammatory cell accumulation in the aortas of mice infused with AngII. It also inhibits AngII-induced activation of matrix metalloproteinase 2(MMP-2) and MMP-9 to maintain elastin content in vivo. In addition, it blocks AngII cascade by downregulating angiotensin type 1 receptor(AT1R) and inhibiting mitogen-activated protein kinases(MAPKs). Taken together, our findings show that BAI is an effective agent for AAA prevention.

关键词： baicalein abdominal aortic aneurysm oxidative stress vascular inflammation extracellular matrix degradation AT1R MAPKs

Systems biomedicine： It＇s your turn --Recent progress in systems biomedicine

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Frontiers of Electrical and Electronic Engineering in China 2013年第2期8卷 140-155页

作者： Zhuqin Zhang Zhiguo Zhao Bing Liu Dongguo Li Dandan Zhang houzao chen Depei Liu State Key Laboratory of Medical Molecular Biology Department of Biochemistry and Molecular Biology Institute of Basic MedicalSciences Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100005 China

The concept of ＂systems biology＂ is raised by Hood in 1999. It means studying all components with a systematic view. Systems biomedicine is the application of systems biology in medicine. It studies all components in a whole system and aims to reveal the patho-physiologic mechanisms of disease. In recent years, with the development of both theory and technology, systems biomedicine has become feasible and popular. In this review, we will talk about applications of some methods of omics in systems biomedicine, including genomics, metabolomics （proteomics, lipidomics, glycomics）, and epigenomics. We will particularly talk about microbiomics and omics for common diseases, two fields which are developed rapidly recently. We also give some bioinformatics related methods and databases which are used in the field of systems biomedicine. At last, some examples that illustrate the whole biological system will be given, and development for systems biomedicine in China and the prospect for systems biomedicine will be talked about.

关键词： Wellcome Trust Case Control Consortium National Human Genome Research Institute Kabuki Syndrome Fetal Hemoglobin Level Ovarian Cancer Association Consortium

Endothelium-specific SIRT1 overexpression inhibits hyperglycemia-induced upregulation of vascular cell senescence

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Science China(Life Sciences) 2012年第6期55卷 467-473页

作者： chen houzao WAN YanZhen ZHOU Shuang LU YunBiao ZHANG ZhuQin ZHANG Ran chen Feng HAO DeLong ZHAO Xiang GUO Zhichen LIU DePei LIANG ChihChuan National Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China Department of Rheumatology and Immunology Peking Union Medical College HospitalBeijing 100005China

The rapidly increasing prevalence of diabetes mellitus worldwide is one of the most serious and challenging health problems in the 21st century. Mammalian sirtuin 1 （SIRT1） has been shown to decrease high-glucose-induced endothelial cell senescence in vitro and prevent hyperglycemia-induced vascular dysfunction. However, a role for SIRTI in prevention of hyperglyce- mia-induced vascular cell senescence in vivo remains unclear. We used endothelium-specific SIRT1 transgenic （SIRT1-Tg） mice and wild-type （WT） mice to construct a 40-week streptozotocin （STZ）-induced diabetic mouse model. In this mode, 42.9% of wild-type （WT） mice and 38.5% of SIRT1-Tg mice were successfully established as diabetic. Forty weeks of hyper- glycemia induced significant vascular cell senescence in aortas of mice, as indicated by upregulation of expression of senes- cence-associated markers including p53, p21 and plasminogen activator inhibitor-1 （PAI-1）. However, SIRT1-Tg diabetic mice displayed dramatically decreased expression of p53, p21 and PAI-I compared with diabetic WT mice. Moreover, man- ganese superoxide dismutase expression （MnSOD） was significantly downregulated in the aortas of diabetic WT mice, but was preserved in diabetic SIRT1-Tg mice. Furthermore, expression of the oxidative stress adaptor p66Shc was significantly de- creased in aortas of SIRT1-Tg diabetic mice compared with WT diabetic mice. Overall, these findings suggest that SIRT 1-mediated inhibition of hyperglycemia-induced vascular cell senescence is mediated at least partly through the reduction of oxidative stress.

关键词： SIRT1 hyperglycemia vascular cell senescence

SIRT1 suppresses PMA and ionomycin-induced ICAM-1 expression in endothelial cells

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Science China(Life Sciences) 2013年第1期56卷 19-25页

作者： JIA YuYan GAO Peng chen houzao WAN YanZhen ZHANG Ran ZHANG ZhuQin YANG RuiFeng WANG Xu XU Jing LIU DePei State Key Laboratory of Medical Molecular Biology Department of Biochemistry and Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences & Peking Union Medical College

Intercellular adhesion molecule-1 （ICAM-1） plays an important role in the recruitment of leukocytes to the endothelium, which causes inflammation and initiation of atherosclerosis. We have previously shown that endothelium-specific over-expression of class III deacetylase SIRT1 decreases atherosclerosis. We therefore addressed the hypothesis that SIRT1 suppresses ICAM-1 expression in the endothelial cells. Here, we found that expression of SIRT1 and ICAM-1 was significantly induced by PMA and ionomycin （PMA/Io） in human umbilical vein endothelial cells （HUVECs）. Adenovirus-mediated over-expression of SIRT1 significantly inhibited PMA/Io-induced ICAM-1 expression （RNAi） resulted in increased expression of ICAM-1 in HUVECs in HUVECs. Knockdown of SIRT1 by RNA interference Luciferase report assay showed that over-expression of SIRT1 suppressed ICAM-1 promoter activity both in basic and in PMA/Io-induced conditions. We further found that SIRT1 was involved in transcription complex binding on the ICAM-1 promoter by chromatin immunoprecipitation （CHIP） assays. Furthermore, SIRT1 RNAi increased NF-~：B p65 binding ability to the ICAM-1 promoter by ChIP assays. Overall, these data suggests that SIRT1 inhibits ICAM-1 expression in endothelial cells, which may contribute to its anti-atherosclerosis effect.

关键词： SIRT1 ICAM-1 PMA and ionomycin

A vascular endothelial growth factor activating transcription factor increases the endothelial progenitor cells population and induces therapeutic angiogenesis in a type 1 diabetic mouse with hindlimb ischemia

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Chinese Medical Journal 2014年第20期127卷 3623-3629页

作者： Diao Yongpeng Lian Lishan Guo Lilong chen houzao chen Yuexin Song Xiaojun Li Yongjun Department of Vascular Surgery Peking Union Medical CollegeHospital Peking Union Medical College Chinese Academy ofMedical Sciences Beijing 100730 China National Laboratory of Medical Molecular Biology Institute of BasicMedical Sciences Peking Union Medical College Chinese Academyof Medical Science Beijing 100730 China

Background Therapeutic angiogenesis has been shown to promote blood vessel growth and improve tissue perfusion. Vascular endothelial growth factor （VEGF） plays an important role in angiogenesis. However, it has side effects that limit its therapeutic utility in vivo, especially at high concentrations. This study aimed to investigate whether an intramuscular injection of a genetically engineered zinc finger VEGF-activating transcription factor modulates the endothelial progenitor cells （EPC） and promotes therapeutic angiogenesis in a hindlimb ischemia model with type 1 diabetes. Methods AIIoxan （intravenous injection） was used to induce type I diabetes in C57BL/6 mice （n=58）. The ischemic limb received ZFP-VEGF （125 pg ZFP-VEGF plasmid in 1% poloxamer） or placebo （1% poloxamer） intramuscularly. Mice were sacrificed 3, 5, 10, or 20 days post-injection. Limb blood flow was monitored using laser Doppler perfusion imaging. VEGF mRNA and protein expression were examined using real-time PCR and ELISA, respectively. Capillary density, proliferation, and apoptosis were examined using immunohistochemistry techniques. Flow cytometry was used to detect the EPC population in bone marrow. Two-tailed Student＇s paired t test and repeated-measures analysis of variance were used for statistical analysis. Results ZFP-VEGF increased VEGF mRNA and protein expression at 3 and 10 days post-injection, and increased EPC in bone marrow at day 5 and 20 post-injection compared with controls （P〈0.05）. ZFP-VEGF treatment resulted in better perfusion recovery, a higher capillary density and proliferation, and less apoptosis compared with controls （P〈0.05）. Conclusions Intramuscular ZFP-VEGF injection promotes therapeutic angiogenesis in an ischemic hindlimb model with type 1 diabetes. This might be due to the effects of VEGF on cell survival and EPC recruitment.

关键词： diabetes endothelial progenitor cell zinc finger protein vascular endothelial growth factor angiogenesis

Vascular Transcriptome Profiling Reveals Aging-Related Genes in Angiotensin Ji-Induced Hypertensive Mouse Aortas

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Chinese Medical Sciences Journal 2020年第1期35卷 43-53页

作者： Shuangjie Lv Yangnan Ding Xiaoya Pei Xiang Zhao Delong Hao Zhuqin Zhang houzao chen Depei Liu State Key Laboratory of Medical Molecular Biology Department of Biochemistry and Molecular BiologyInstitute of Basic Medical Sciences Chinese Academy of Medical Sciences&School of Basic Medicine Peking Union Medical CollegeBeijing 100005China

Objective AngiotensinⅡ(AngⅡ)-induced vascular damage is a major risk of ***,the underlying molecular mechanism of AngⅡ-induced vascular damage is still *** this study,we explored the novel mechanism associated with Ang Il-induced *** We treated 8-to 12-week-old C57BL/6J male mice with saline and AngⅡ(0.72 mg/kg-d)for 28 days,*** the RNA of the media from the collected mice aortas was extracted for transcriptome *** component analysis was applied to show a clear separation of different samples and the distribution of differentially expressed genes was manifested by Volcano *** annotations including Gene Ontology(GO)and Koto Encyclopedia of Genes and Genomes(KEGG)pathway were performed to reveal the molecular mechanism of AngⅡ-induced ***,the differentially expressed genes were validated by using quantitative real-time *** The result revealed that a total of 773 genes,including 599 up-regulated genes and 174 down-regulated genes,were differentially expressed in the aorta of AngⅡ-induced hypertension mice *** analysis of differentially expressed genes manifested that various cellular processes may be involved in the AngⅡ-induced hypertension,including some pathways associated with hypertension such as extracellular matrix,inflammation and immune ***,we also found that the differentially expressed genes were enriched in vascular aging pathway,and further validated that the expression levels of insulin-like growth factor 1 and adiponectin were significantly increased(P<0.05).Conclusion We identify that vascular aging is involved in AngⅡ-induced hypertension,and insulin-like growth factor 1 and adiponectin may be important candidate genes leading to vascular aging.

关键词： hypertension vascular aging angiotensin II transcriptome sequencing

Nuclear expression of Mitochondrial transcription factor A might influence the mRNA level of itself

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Nuclear expression of Mitochondrial transcription factor A m...