DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Koh, Gou Young | - |
dc.contributor.advisor | 고규영 | - |
dc.contributor.author | Lee, Seung-Jun | - |
dc.contributor.author | 이승준 | - |
dc.date.accessioned | 2018-05-23T19:36:48Z | - |
dc.date.available | 2018-05-23T19:36:48Z | - |
dc.date.issued | 2017 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=675792&flag=dissertation | en_US |
dc.identifier.uri | http://hdl.handle.net/10203/241979 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 의과학대학원, 2017.2,[iv, 74 p. :] | - |
dc.description.abstract | Part I. Amelioration of Sepsis by Tie2 Activation Induced Vascular Protection Protection of endothelial integrity has been recognized as a front line approach to mitigate sepsis progression, yet no effective agent for preserving endothelial integrity is available. Here I show that the activation of endothelial receptor Tie2 protects vasculature from septic dam-age and provides survival benefit in an experimental sepsis model using a unique anti-angiopoietin-2 (Ang2) antibody named as ABTAA (Ang2 Binding and Tie2 Activating Anti-body). Upon binding to Ang2, ABTAA renders clustering of Ang2, assembling an AB-TAA/Ang2 complex that can subsequently bind and activate Tie2. Compared with a conven-tional Ang2 blocking antibody, ABTAA was highly effective in delaying sepsis progression by strengthening the endothelial glycocalyx | - |
dc.description.abstract | reducing cytokine storms, vascular leakage, and rarefaction | - |
dc.description.abstract | and mitigating organ damages. Together, my data establishes the ameliorative role of Tie2 activation in sepsis progression, proposing a therapeutic avenue for sepsis amidst the unavailability of sepsis-specific treatments. Part II. Amelioration of post-ischemic cardiac remodeling through Ang-Tie2 signaling Although acute mortality of myocardial infarction (MI) remarkably reduced by primary PCI, about 10% of MI survivors die in 18 months and 25% of survivor suffer from heart failure as a sequelae of MI. Although, prompt recanalization is the most important goal in rescuing MI patient, restoration of blood flow per se contributes to cardiomyocyte death by inducing oxi-dative stress and inflammation, called “lethal reperfusion injury”. In this study, utilizing genet-ically modified mice and anti-angiopoietin-2 (Ang2) antibody, I show that endothelial cell de-rived Ang2 plays a crucial role in augmenting post-ischemic adverse cardiac remodeling. Ang2 was expressed in the endothelial cells of infarction border zone and ischemia-reperfusion (I/R) area 2 days after ischemia. Endothelial cell specific deletion of Ang2 markedly reduced vascu-lar leakage, adhesion molecule expression, neutrophil infiltration, increased pericyte coverage and effective perfusion. Consequently EC-specific deletion of Ang2 significantly ameliorated cardiac hypoxia and infarct progression. Similar findings were observed by administration of anti-Ang2 antibody. My data elucidated the ameliorating role of Ang2 in post-ischemic cardi-ac remodeling, and presents a noble approach to mitigate the injury by Ang2 neutralization. | - |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | sepsis | - |
dc.subject | vascular leakage | - |
dc.subject | pericyte | - |
dc.subject | glycocalyx | - |
dc.subject | Tie2 | - |
dc.subject | myocardial infarction | - |
dc.subject | ischemia-reperfusion | - |
dc.subject | cardiac remodeling | - |
dc.subject | foxo1 | - |
dc.subject | angiopoietin-2 | - |
dc.subject | 패혈증 | - |
dc.subject | 혈액 누출 | - |
dc.subject | 주변 세포 | - |
dc.subject | 내피세포 표면층 | - |
dc.subject | Tie2 수용체 | - |
dc.subject | 심근 경색 | - |
dc.subject | 허혈-재관류 | - |
dc.subject | 혈관 염증 | - |
dc.title | Ameliorating role of Tie2 activation in vascular diseases | - |
dc.title.alternative | Tie2 활성화를 통한 혈관 질환의 새로운 치료 방법 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 325007 | - |
dc.description.department | 한국과학기술원 :의과학대학원, | - |
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