Ying Yu

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Name: 余鹰; Ying Yu

Organization: Shanghai Tech University

Department: Institute for Translational Medicine and Therapeutics

Title: Professor

Chemicals
References

Aspirin enhances protective effect of fish oil against thrombosis and injury-induced vascular remodelling

Co-reporter:Yanjun Gong;Minghui Lin;Lingjuan Piao;Xinzhi Li;Fei Yang;Jian Zhang;Bing Xiao;Qingli Zhang;Wen-Liang Song;Huiyong Yin;Li Zhu;Colin D Funk

British Journal of Pharmacology 2015 Volume 172( Issue 23) pp:5647-5660

Publication Date(Web):

DOI:10.1111/bph.12986

Background and Purpose

Although aspirin (acetylsalicylic acid) is commonly used to prevent ischaemic events in patients with coronary artery disease, many patients fail to respond to aspirin treatment. Dietary fish oil (FO), containing ω3 polyunsaturated fatty acids (PUFAs), has anti-inflammatory and cardio-protective properties, such as lowering cholesterol and modulating platelet activity. The objective of the present study was to investigate the potential additional effects of aspirin and FO on platelet activity and vascular response to injury.

Experimental Approach

Femoral arterial remodelling was induced by wire injury in mice. Platelet aggregation, and photochemical- and ferric chloride-induced carotid artery thrombosis were employed to evaluate platelet function.

Key Results

FO treatment increased membrane ω3 PUFA incorporation, lowered plasma triglyceride and cholesterol levels, and reduced systolic BP in mice. FO or aspirin alone inhibited platelet aggregation; however, when combined, they exhibited synergistic suppression of platelet activity in mice, independent of COX-1 inhibition. FO alone, but not aspirin, attenuated arterial neointimal growth in response to injury. Strikingly, a combination of FO and aspirin synergistically inhibited injury-induced neointimal hyperplasia and reduced perivascular inflammatory reactions. Moreover, co-administration of FO and aspirin decreased the expression of pro-inflammatory cytokines and adhesion molecules in inflammatory cells. Consistently, a pro-resolution lipid mediator-Resolvin E1, was significantly elevated in plasma in FO/aspirin-treated mice.

Conclusions and Implications

Co-administration of FO and low-dose aspirin may act synergistically to protect against thrombosis and injury-induced vascular remodelling in mice. Our results support further investigation of adjuvant FO supplementation for patients with stable coronary artery disease.

Linked Articles

This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23

Chronic Cardiovascular Disease-Associated Gene Network Analysis in Human Umbilical Vein Endothelial Cells Exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin

Co-reporter:Yu Yu;Jing Qin;Di Chen;Hui Wang;Junwen Wang

Cardiovascular Toxicology 2015 Volume 15( Issue 2) pp:157-171

Publication Date(Web):2015 April

DOI:10.1007/s12012-014-9279-6

The association of dioxin exposure with increased morbidity or mortality of chronic cardiovascular diseases (CVDs) has been established by many epidemiological studies. However, the precise global gene expression alterations caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the cardiovascular system need to be further elucidated. In this study, we profiled the gene expression of human umbilical vein endothelial cells (HUVECs) exposed to different concentrations of TCDD by high-throughput sequencing. Expression of 1,838 genes was changed significantly after TCDD stimulation. The FunDO analysis suggested that some CVDs were highly associated with TCDD treatment, including atherosclerosis, thromboangiitis obliterans, pulmonary arterial hypertension (PAH), and hypertension. KEGG pathway analysis showed that many genes in the signaling pathways of vascular smooth muscle contraction and apoptosis were altered distinctly. In addition, we revealed evidence regarding the gene network changes of chronic CVDs including atherosclerosis, thrombosis, myocardial infarction (MI), hypertension, and PAH in TCDD-exposed HUVECs. We found that gene expression of β1-adrenoceptors (ADRB1), β2-adrenoceptors (ADRB2), endothelin-converting enzyme 1 (ECE1), and endothelin-1 gene (EDN1) that are involved in the blood pressure regulation pathway decreased apparently under TCDD treatment. Moreover, the transcripts of interleukin 1 beta (IL-1β) and tumor necrosis factor α (TNFα), which are related to atherosclerosis, were up-regulated by TCDD stimulation. In addition, the transcripts of Homo sapiens collagen, type IV, alpha 1 (COL4A1), and isoforms that trigger the MI pathway were up-regulated after TCDD exposure. Finally, we found enhanced platelet-derived growth factor (PDGF) and signal transducer and activator of transcription 5 (Stat5) expression with TCDD treatment in endothelial cells, which are involved in PAH induced by vascular injury.

Vascular COX-2 Modulates Blood Pressure and Thrombosis in Mice

Co-reporter:Ying Yu;Irene Crichton;Soon Yew Tang;Gregory Grant;Gavin Landesberg;Weichen Wu;Ellen Puré;Garret A. FitzGerald;Rosario Scalia;Zhou Yu;Emanuela Ricciotti;Colin D. Funk

Science Translational Medicine 2012 Volume 4(Issue 132) pp:132ra54

Publication Date(Web):02 May 2012

DOI:10.1126/scitranslmed.3003787

Deletion of vascular COX-2 predisposes mice to thrombosis and hypertension.

Myeloid-derived suppressor cell function is diminished in aspirin-triggered allergic airway hyperresponsiveness in mice

Co-reporter:Maohua Shi, Guochao Shi, Juan Tang, Deping Kong, ... Ying Yu

Journal of Allergy and Clinical Immunology (November 2014) Volume 134(Issue 5) pp:1163-1174.e16

Publication Date(Web):1 November 2014

DOI:10.1016/j.jaci.2014.04.035

BackgroundMyeloid-derived suppressor cells (MDSCs) have recently been implicated in the pathogenesis of asthma, but their regulation in patients with aspirin-intolerant asthma (AIA) remains unclear.ObjectiveWe sought to characterize MDSC accumulation and pathogenic functions in allergic airway inflammation mediated by COX-1 deficiency or aspirin treatment in mice.MethodsAllergic airway inflammation was induced in mice by means of ovalbumin challenge. The distribution and function of MDSCs in mice were analyzed by using flow cytometry and pharmacologic/gene manipulation approaches.ResultsCD11b+Gr1highLy6G+Ly6Cint MDSCs (polymorphonuclear MDSCs [PMN-MDSCs]) recruited to the lungs are negatively correlated with airway inflammation in allergen-challenged mice. Aspirin-treated and COX-1 knockout (KO) mice showed significantly lower accumulation of PMN-MDSCs in the inflamed lung and immune organs accompanied by increased TH2 airway responses. The TH2-suppressive function of PMN-MDSCs was notably impaired by COX-1 deletion or inhibition, predominantly through downregulation of arginase-1. COX-1–derived prostaglandin E2 promoted PMN-MDSC generation in bone marrow through E prostanoid 2 and 4 receptors (EP2 and EP4), whereas the impaired arginase-1 expression in PMN-MDSCs in COX-1 KO mice was mediated by dysregulation of the prostaglandin E2/EP4/cyclic AMP/protein kinase A pathway. EP4 agonist administration alleviated allergy-induced airway hyperresponsiveness in COX-1 KO mice. Moreover, the immunosuppressive function of PMN-MDSCs from patients with AIA was dramatically decreased compared with that from patients with aspirin-tolerant asthma.ConclusionThe immunosuppressive activity of PMN-MDSCs was diminished in both allergen-challenged COX-1 KO mice and patients with AIA, probably through an EP4-mediated signaling pathway, indicating that activation of PMN-MDSCs might be a promising therapeutic strategy for asthma, particularly AIA.