Recently, Yuzhen Zhang’s team from State Key laboratory of Cardiovascular Diseases, Tongji University School of Medicine, Shanghai East Hospital Affiliated to Tongji University has made great progress in cardiovascular research under the leadership of Zhongmin Liu, President of Shanghai East Hospital, with their researches published in AHA authoritative journals Circulation, Circ Res and Arterioscler Thromb Vasc Biol. They revealed critical regulatory mechanisms of transcriptional factors in cardiac failure, arteriosclerosis and vascular restenosis. With collaboration of Prof.Cheng Yu from The Institute for Biomedical Engineering and Nano Science, TUSM, they developed nanomaterials targeting vascular endothelium and successfully achieved targeted gene regulation of endothelial cells. They reversed pathological myocardial remodeling and delayed occurrence and development of arteriosclerosis by precisely regulating target gene expression in endothelial cells, providing important knowledge for preventing and treating coronary heart disease, heart failure and restenosis after vascular injury.

Photo of Yuzhen Zhang and her team

Zhang Yuzhen’ s research team published one of their researches online in Arterioscler Thromb Vasc Biol on April 4, 2019. This research article reveals the critical function of transcriptional factor GATA6 in regulation of vascular endothelial proliferation after vascular injury. The research shows smooth muscle-specific GATA6 knockout significantly increases endothelial proliferation, whereas endothelial cell-specific GATA6 knockout significantly decreases endothelial proliferation. Further study shows in vascular smooth muscle GATA6 upregulates expression of cellular matrix protein CCN5 to inhibit endothelial proliferation, whereas in endothelial cells GATA6 upregulates expression of PDGF-B to promote proliferation and migration of smooth muscle in paracrine manner and thus exacerbate endothelial proliferation. This research helps us to further understand molecular mechanism of vascular endothelial proliferation after stent implantation and provides us with new ideas for discovering drug target of restenosis after stent implantation. The first authors are postdoctor Zhuang Tao, associate research fellow Liu Jie and research assistant Chen Xiaoli from Shanghai East Hospital affiliated to Tongji University. The correspondence authors are Liu Zhongmin, President of Shanghai East Hospital, Prof. Zhang Yuzhen and research fellow Lin Zhang. The work is supported by National Natural Science Foundation, National Key Research and Development Program, Science and Technology Commission of Shanghai Municipality and Outstanding Leaders Training Program of Pudong Health Bureau of Shanghai.

Link：https://www.ahajournals.org/doi/10.1161/ATVBAHA.118.312263

Again, another research of this team was published online in first class journal in cardiovascular research Circulation on July 18, 2019. This work reveals that regulatory network of transcription factor Klf2-Foxp1 plays an important role in regulating inflammation body complex activation to control occurrence and development of arteriosclerosis. They find that expression of Foxp1 decreases dramatically in arteriosclerosis and susceptible area and endothelial cell-specific Foxp1 knockout significantly increases arteriosclerosis while overexpression of Foxp1 in endothelial cell inhibits occurrence of arteriosclerosis. Further study shows that Foxp1 negatively regulates inflammation body complex Nlrp3-Caspase1-IL1β to delay occurrence and development of arteriosclerosis. In addition, this ream found that Foxp1 is responsive to change of shear force of blood flow, revealing important molecular mechanism of blood flow shear force affecting occurrence and development of arteriosclerosis. More importantly, this team found that statins can induce expression of Klf2 and Foxp1, revealing that novel mechanism of statins treating arteriosclerosis and thus providing new evidence and ideas for coronary heart disease therapy. This work received attention and positive reviews from academic peers at home and abroad with commentary and recommendation of Gregory B. Lim, chief editor of top review journal in cardiology, Nature Reviews Cardiology. The first authors are postdoctor Zhuang Tao, associate research fellow Liu Jie and research assistant Chen Xiaoli from Shanghai East Hospital affiliated to Tongji University. The correspondence authors are Prof. Liu Yuzhen and Prof. Liu Zhongmin from Shanghai East Hospital affiliated to Tongji University and Prof. Muredach Reilly from Columbia University. This work received great support of Prof. Cheng Yu from Institute for Biomedical Engineering and Nano Science, Tongji University and Prof. Wang Haikun from Key Laboratory of Molecular Virology and Immunology, Chinese Academy of Sciences and was supported by National Natural Science Foundation, National Major Program of Development Fund, Science and Technology Commission of Shanghai Municipality and Outstanding Leaders Training Program of Pudong Health Bureau of Shanghai.

link：https://www.ahajournals.org/doi/abs/10.1161/CIRCRESAHA.118.314402

Good news again from Yuzhen Zhang’ research team—top journal in cardiology Circulation published the team’s another research on June 10, 2019. The team identified a key transcription factor Foxp1 in regulation of pathological cardiac remodeling. Endothelial cell-specific knockout of Foxp1 exacerbates pathological cardiac remodeling and reduces cardiac function, while endothelial cell-specific overexpression of Foxp1 ameliorates pathological cardiac remodeling and improves cardiac function. The team dissected that TGFβ1 signal pathway is Foxp1’s  downstream target and inhibitors of TGFβ can reverse cardiac remodeling caused by Foxp1 deficiency. Systemic inhibition of TGFβ could reverse pathological cardiac remodeling, although there was an increase in mortality of laboratory animals. As a result, the team used RGD-peptide magnetic nanoparticle target delivery of TGF-β1–siRNA to ECs and validated endothelial cell-specific inhibition of TGFβ can ameliorate pathological cardiac remodeling and cardiac dysfunction, providing new ideas and methods for preventing and treating heart failure. The first authors are associate research fellow Liu Jie, postdoctor Zhuang Tao and clinician Pi Jinjiang from Shanghai East Hospital affiliated to Tongji University. The correspondence authors are Prof. Zhang Yuzhen, Prof. Liu Zhogmin and research fellow Zhang Lin from Shanghai East Hospital affiliated to Tongji University. This work received great support of Prof. Cheng Yu from Institute for Biomedical Engineering and Nano Science, Tongji University and Prof. Wang Haikun from Key Laboratory of Molecular Virology and Immunology, Chinese Academy of Sciences and was supported by National Natural Science Foundation, National Major Program of Development Fund, Science and Technology Commission of Shanghai Municipality and Outstanding Leaders Training Program of Pudong Health Bureau of Shanghai.

Link: https://www.ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.119.039767

These researches were primarily accomplished in Tongji University. Within 5 years only, Yuzhen Zhang’s team has built systematic animal models of coronary heart disease and vascular lesion, introduced and established varieties of tool mice and transgenic mice, systematically completed research system of coronary disease and vascular lesion and set up world-class research system of coronary heart disease and vascular lesion. In the last 5 years, this team has got grants from 7 General Programs, 2 Young Scientists Funds, 1 Major Research Plan of NNSF and 1 National Basic Research Program of China (973 Program) of Ministry of Science and Technology. The team has published 9 SCI indexed articles, including 1 in Circulation, 2 in Cir Res, 1 in Arterioscler Thromb Vasc Biol and 1 in Theranostics with a cumulative impact factor of 87.  

Notes: Circulation is ranked No. 2 in cardiology journals of an impactor factor 23.054, Nature Reviews Cardiology No. 4 of 17.420 and Cir Res No. 5 of 15.862.