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Myosin ⅡA-mediated endothelial exocytosis is critical for vascular homeostasis

Myosin ⅡA-mediated endothelial exocytosis is critical for v...

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中国生理学会基质生物学专业委员会第二次全国基质生物学学术会议

作者： Pin Li 魏国琴 Yang Cao Qiuping Deng Xiaoshuai Huang Yingqing Huo Liangyi Chen Jincai Luo Laboratory of Vascular Biology Institute of Molecular MedicinePeking University 北京大学分子医学研究所 Beijing Key Laboratory of Cardiometabolic Molecular Medicine Institute of Molecular MedicinePeking University

The exocytosis of vascular endothelial cells is critical to maintaining the homeostasis of the blood ***-Palade bodies(WPBs)are endothelial-specific granules containing various bioactive molecules,including von Willebrand factor(VWF)and P-selectin,which regulate both the angiogenesis and the interaction with surrounding cells or *** previous work revealed that the focal adhesion(FA)protein zyxin promotes the

关键词： A-mediated endothelial exocytosis is critical for vascular homeostasis Myosin

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Endothelium derived Notch signal promotes liver sinusoidal endothelial cell senescence and blunts angiocrine to hamper liver regeneration in an eNOS-Wnt2a dependent manner

Endothelium derived Notch signal promotes liver sinusoidal e...

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中国生理学会基质生物学专业委员会第二次全国基质生物学学术会议

作者：王琳第四军医大学西京医院肝胆外科暨全军器官移植研究所

Background&Aims:Liver sinusoid endothelial cells(LSECs)play pivotal roles in liver *** regulates vessel *** of Notch signaling results in hepatic vascular *** current study aimed at further clarifying the roles and mechanisms of Notch signaling in LSECs in steady state and ***:Liver regeneration was induced by partial hepatectomy(PHx).Notch signaling was activated by

关键词： Notch Endothelium derived Notch signal promotes liver sinusoidal endothelial cell senescence and blunts angiocrine to hamper liver regeneration in an eNOS-Wnt2a dependent manner Wnt

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The Mammalian Target of Rapamycin and DNA methyltransferase 1 axis mediates vascular endothelial dysfunction in response to disturbed flow

The Mammalian Target of Rapamycin and DNA methyltransferase ...

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中国生理学会基质生物学专业委员会第二次全国基质生物学学术会议

作者：张云鹏 Yi-Tao Huang Wei Pang Juan-Juan Zhu Yue-Feng Liu Jing Zhou 北京大学医学部 Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking University Key Laboratory of Molecular Cardiovascular Science Ministry of Education

Objective:Vascular endothelial cells(ECs)are constantly exposed to shear stress induced by circulatingblood flow,but the mechanism of flow-pattern-specific modulation of endothelial function remains *** study aims to demonstrate the role of DNA methyltransferase 1(DNMT1)-dependent DNA methylation in the flow-regulation of endothelial function as well as the detailed signaling mechanism.

关键词： The Mammalian Target of Rapamycin and DNA methyltransferase 1 axis mediates vascular endothelial dysfunction in response to disturbed flow Target DNA

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Mitochondrial Resident Cartilage Oligomeric Matrix Protein Inhibits VSMCCalcification Via Interacting With PHB2

Mitochondrial Resident Cartilage Oligomeric Matrix Protein I...

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中国生理学会基质生物学专业委员会第二次全国基质生物学学术会议

作者：贾一挺 Meili Wang Fu Yi Wei Kong 北京大学医学部 Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking University Key Laboratory of Molecular Cardiovascular Science Ministry of Education

Background:VSMC calcificationis highly related to cardiovascular morbidity and mortality among aging individuals and patients with chronic renal failure and diabetes *** dedifferentiation of VSMC exerting as chondrocyte/osteoblast phenotype mainly contributes to VSMC *** oligomeric matrix protein(COMP) inhibits VSMC calcification,but the underlie mechanism of COMP-inhibited VSMC calcification is still not fully *** and Results:Microarray profiling and bioinformatic analysis of WT and COMP-/-VSMCs revealed that COMP-deficient VSMCs exerted impaired oxidative *** in vitro studies confirmed that COMP deficiency caused mitochondrial oxidative phosphorylation dysfunction,morphological abnormality,impaired ATP synthesis,and mitochondrial fission rather *** using immunofluorescence assay,we found COMP localized inmitochondria,further confirmed by western blot analysis showing that COMP was present in purified mitochondrial *** interactome of COMP identified that COMP interacted with mitochondrial resident protein prohibitin 2(PHB2).COMP directly bound to prohibitin 2 C-terminal via its *** to COMP deficiency,PHB2-deficient VSMC exhibited loss of contractile phenotype and aggravated high phosphate-induced ***,adenovirus-mediated COMP overexpression promoted mitochondrial oxidative phosphorylation,which was partly abolished upon PHB2 ***:Our study indicated that COMP inhibited VSMC calcification through its interaction with PHB2 to maintainmitochondrialhomeostasis and the contractile phenotypic of VSMCs.

关键词： VSMC calcification COMP PHB2 mitochondrial VSMC phenotypic modulation

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Cartilage OligomericMatrix Protein Induce Embryonic Stem Cell Differentiation into Mature Vascular Smooth Muscle Cells via activating Notch Signaling

Cartilage OligomericMatrix Protein Induce Embryonic Stem Cel...

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中国生理学会基质生物学专业委员会第二次全国基质生物学学术会议

作者：马百荟 Yi Fu Wei Kong 北京大学医学部 Department of Physiology and Pathophysiology Peking University Health Science Center

Background:The differentiation of stem cells into vascular smooth muscle cell(VSMC)pIays a critical role in vascular development and *** oligomeric matrix protein(COMP) is able to inhibit the dedifferentiation of VSMCs and maintain the contractile phenotype of ***,the role of COMP in vascular development is still ***:To investigate whether COMP contributes to the differentiation of embryonic stem cells into *** and Results:Purified COMP protein upregulated the expressions of VSMC markers including SM22,SMA and CNN in time-dependent manner at both protein and mRNA levels in mouse embryonic stem cells(mESCs)as demonstrated by western blot and RT-PCR ***,cell contractile assay demonstrated that mESCs induced by COMP protein for 7 days also exhibited the comparable contractile property as mature VSMCs,indicating COMP induced the differentiation of ESCs into mature ***,COMP treatment significantly enhanced the NICD protein expression as well as Notch signaling target genes Heyl and Hey2 mRNA levels,implying COMP activated Notch *** of Notch antagonist DAPT or dominant negative MAML markedly inhibited COMP-induced VSMC markers expressions,suggesting that Notch signaling mediated COMP-induced mESC-VSMC ***,luciferase assay demonstrated COMP activated Notch signaling target gene transcription without modulating the expressions of ligands and receptors,while co-immunoprecipitation displayed the direct interaction between COMP and Notch,indicating COMP may directly activated Notch signaling as a novel Notch ***:COMP induces the differentiation of mESCs into VSMCs via directly activating Notch signaling.

关键词： stem cells COMP Notch VSMCs

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Correlation Between Serum Nε-carboxymethyl-lysine and Anterior Tibial Arterial Plaque Calcification in Patients with Diabetic Foot Amputation

Correlation Between Serum Nε-carboxymethyl-lysine and Anter...

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中国生理学会基质生物学专业委员会第二次全国基质生物学学术会议

作者：叶斐 Xu Sui-ning Bao Zheng-yang Sun Zhen Yan Jin-chuan Wang Zhong-qun 江苏大学 Department of Cardiology Affiliated Hospital of Jiangsu University

Objective To observe the correlation between the main components of advanced glycation end products Nε-carboxymethyl-Lysine(CML) and the calcification of the anterior tibial artery plaque in patients with diabetic foot *** Sixty patients hospitalized for diabetic foot amputation in the Department of Orthopedics,Affiliated Hospital of Jiangsu University were recruited from June 2012 to June *** patients were categorized based on the severity of anterior tibial artery stenosis assessed by color Doppler ultrasound,into mild stenosis group(0%

关键词： Diabetic Foot Amputation Plaque Calcification Nε-carboxymethyl-Lysine

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Phenotype and Chemokine Receptor Expression of Different Monocyte Subsets Affect Atherosclerotic Plaque Microenvironment in ApoE-/- Mouse

Phenotype and Chemokine Receptor Expression of Different Mon...

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中国生理学会基质生物学专业委员会第二次全国基质生物学学术会议

作者：杨柳 Yuanyuan An Ji Yang Haibo Zhu 中科院药物研究所 State Key Laboratory for Bioactive Substances and Functions of Natural Medicines Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation StudyInstitute of Materia MedicaChinese Academy of Medical Sciences & Peking Union Medical College Medical School of the University of South China

Monocytes circulate in blood,bone marrow and spleen,and eventually migrate into tissue in response to tissue-derived signals,phagocyte toxic molecules and other *** lines the interior surface of blood vessels,forming an interface between circulating blood and the rest of the vessel *** usually remains silent until the integrity of the arterial surface is breakdown by primary triggers,such as oxidized lipids and *** triggers up-regulate tissue factor expression,ICAM-1 and VCAM-1 expression,induce the release of IL-6,IL-8 and MCP-1 by *** system responds to the endothelium injury and blood monocytes are recruited into intima and *** our study,markers CD43 and Ly6 C were used to subdivide different types of monocytes,including Classical Ly6 C++CD43+ monocytes,Intermediate Ly6 C++CD43++monocytes,and Non-classical Ly6 C+CD43++ monocytes,and the chemokine receptor expression of these subtypes were *** observed the anti-atherosclerosis effect of Atorvastatin,Terutroban and IMM-H007,and find out the relationships between plaque vulnerability and monocytes subtype *** with chow diet apoE-/-mouse,after high cholesterol and high fat diet,Classical monocytes in blood were decreased significantly and Nonclassical monocytes increased ***2 and CX3 CR1 expression in Classical monocytes increased,but after drug therapy the expression level of these two chemokine receptors decreased *** plaque microenvironment analysis was accomplished by Movat pentachrome stain,oil red O stain,picrosirius red stain,CD68 stain(recognition of lesional macrophages),CD31 stain(recognition of endothelium),a actin stain(recognition of smooth muscle cells).After high cholesterol and high fat,morphology of lesions in aortic arch proximal side showed prominent necrotic core and lipid accumulation,overlying thin fibrous caps,in some section plaque rupture could be ***

关键词： Monocyte Subsets Plaque Microenvironment CCR2 CX3CR1 Plaque Rupture

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Deficiency of Hypoxia Inducible Factor 2α(HIF2α) in Vascular Smooth Muscle Cells(VSMC) Protects Against AngiotensinⅡ-Induced Abdominal Aortic Aneurysm(AAA) in ApoE-/-Mice

Deficiency of Hypoxia Inducible Factor 2α(HIF2α) in Vascul...

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中国生理学会基质生物学专业委员会第二次全国基质生物学学术会议

作者：宋妍婷 Dan Qi Xia Wang Ye Liu Huihua Li Jie Du Aijuan Qu 首都医科大学 Department of Physiology and Pathophysiology School of Basic Medical SciencesCapital Medical University Key Laboratory of Remodeling-Related Cardiovascular Diseases Ministry of Education Beijing Anzhen Hospital of Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases

Background:Uncontrolled growth of abdominal aortic aneurysms(AAA) is a life-threatening vascular disease without an effective pharmacological *** studies suggest that hypoxia may exist in this ***,the contribution of hypoxia to the development of AAA and the underlying mechanisms remain ***:In this study,we sought to investigate the role of hypoxia inducible factor 2α(HIF2α),a key transcription factor mediating cellular adaptive responses to hypoxia,in AAA formation and the underlying mechanisms linking VSMC depletion and *** and Results:Hypoxic niche and HIF2α expression were evaluated in human AAA samples and angiotensin Ⅱ(Ang Ⅱ)-induced AAA models in ApoE-/-*** probe and HIF2α were colocalized withα-SMA,a marker for VSMCs in AAA vessels,indicating that HIF2α is activated in vascular smooth muscle *** explore the role of HIF2α in the development of AAA,VSMC-specificHIF2α knockout mice(Hif2α△SMC)were established and crossed with ApoE-/-mice to generate Hifα△SMC/ApoE-/-mice or the littermate Hif2αF/F/ApoE-/-*** spontaneous AAA formation were observed in either Hif2α△SMC/ApoE-/-or Hif2αF/F/ApoE-/-mice at 12 weeks-old without ***,when infused with Ang Ⅱ at a dosage of1000 ng/kg/min for 28 days,Hif2αF/F/ApoE-/-mice exhibited significantly higher arterial blood pressure compared with Hif2α△SMC/ApoE-/-mice(157.50 ± 4.05 mmHgvs112.90 ± 3.55 mmHg,n=15,p<0.0001) as determined by tail-off *** analyses demonstrated a remarkable dilation of abdominal aortas in Hif2αF/F/ApoE-/-mice than in Hif2α△SMC/ApoE-/-mice(1.57 ± 0.09 mmvsl.04 ± 0.05 mm,n=15,p<0.0001).There were significant declines for the incidence of AAA formation(5.88%vs 89.5%,n=15) and rupture(0%vs 28.6%,n=15)in Hif2α△SMC/ApoE-/-mice than in Hif2αF/F/ApoE-/-mice,suggesting that disruption of HIF2α in VSMCs abrogates AAA ***,there was a dramatic decrease of inflammatory cell infiltration in Hif2α△ SMC

关键词： Abdominal aortic aneurysm Hypoxia Hypoxia inducible factor 2α Smooth muscle cells Apoptosis Inflammation

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Cyclophilin A Signaling Induces Pericyte-associated Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage

Cyclophilin A Signaling Induces Pericyte-associated Blood-Br...

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中国生理学会基质生物学专业委员会第二次全国基质生物学学术会议

作者： Pengyu Pan Hengli Zhao Xuan Zhang Qiang Li Jie Qu Shilun Zuo Fan Yang John H.Zhang Haiyang He Xin Liu Hua Feng 陈渝杰 Department of Neurosurgery Southwest HospitalThird Military Medical University Department of Pathophysiology and High Altitude Pathology College of High Altitude Military MedicineThird Military Medical University Neuroscience Research Center Loma Linda University Institute of Immunology Third Military Medical University 第三军医大学

Within vascular neural network,blood-brain barrier damage contributes to vasogenic brain edema,which is one of the most common pathophysiological changes after SAH and has become a focus of interest in the development of novel therapeutic strategies for SAH ***,the potential roles of pericytes in maintaining the integrity of the blood-brain barrier following SAH and the exact mechanisms of this process,which would be helpful for the development of therapeutic strategies,remain *** the present study,we sought to provide evidence on the potential role of pericytes in blood-brain barrier disruption and the possible involvement and mechanism of CypA signaling in both cultured primary pericytes and SAH *** hundred and ninety-four(394) adult male C57 B6 J mice weighing 22 to 30 g,30 CypA knockout(CypA-/-) mice,and 30 male neonatal C57 B6 J mice were used to investigate the time course of CypA expression in pericytes after SAH,the intrinsic function and mechanism of CypA in the pericytes,and whether the known receptor CD147 mediates the effects of *** data demonstrated that both intracellular CypA and CypA secretion increased after SAH and could activate its receptor CD147 and the downstream NF-κB inflammatory pathway to induce MMP-9 expression and proteolytic functions for the degradation of endothelium tight junction proteins and basal *** served as an autocrine or a paracrine ligand for its receptor,*** CypA could be endocytosed by pericytes,the specific endocytosis inhibitor chlorpromazine did not have an effect on MMP-9 activation following blood-brain barrier ***,the specific knockdown of CD 147 could reverse the harmful effects of CypA expression in the pericytes on the blood-brain barrier integrity after *** study demonstrated for the first time that CypA is elevated in the pericytes of the brain after SAH,and extraneous recombinant CypA damages the blood-brain barrier and diminishes the ne

关键词： Subarachnoid hemorrhage pericyte Cyclophilin A Blood-Brain Barrier endocytosis CD147

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