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Shear Stress-Induced Phenotypic Alterations in Monocytes: Exploring Rheometer Shear and ACE2 Dysregulation Effects
Shear Stress-Induced Phenotypic Alterations in Monocytes: Exploring Rheometer Shear and ACE2 Dysregulation Effects
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211151355
- ISBN
- 9798382342320
- DDC
- 660
- 서명/저자
- Shear Stress-Induced Phenotypic Alterations in Monocytes: Exploring Rheometer Shear and ACE2 Dysregulation Effects
- 발행사항
- [Sl] : Carnegie Mellon University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 84 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-11, Section: B.
- 주기사항
- Advisor: Wayne, Elizabeth C.
- 학위논문주기
- Thesis (Ph.D.)--Carnegie Mellon University, 2024.
- 초록/해제
- 요약Due to the increasing population of individuals with cardiovascular diseases and related comorbidities, there is a growing need for the development of synergistic therapeutics. Monocytes are implicated in a broad spectrum of diseases and can serve as a focal point for therapeutic targeting. Monocytes are members of the mononuclear phagocyte system involved in pathogen clearance and nanoparticle pharmacokinetics. Monocytes play a critical role in the development and progression of cardiovascular diseases. While studies have investigated the effect of nanoparticle modulation on monocyte uptake, their physiological responses to the shears associated with cardiovascular diseases have not been largely studied. In this thesis, we set out to determine the effect of shear on monocytes in varying physiological and mechanical models. The impact of ACE2 deficiency was explicitly investigated in the monocyte's ability to uptake nanoparticles.Moreover, we investigated nanoparticle uptake as a function of nanoparticle size, physiological shear stress, and monocyte ACE2 expression. Higher shear stress exposure increased nanoparticle uptake in ACE2- cells but not in wild-type cells. In addition, the shear stress and nanoparticle uptake appeared to downregulate gene expression more dramatically in ACE2- cells. Our data demonstrates that ACE2- cells exhibit different sensitivities to the same nanoparticle systems. Observing how nanoparticles can modulate monocytes in the context of disease can inform precision dosing. This work demonstrates the benefits of adding more physiologically relevant conditions to in vitro cultures to better inform disease studies, specifically in cardiovascular diseases.
- 일반주제명
- Chemical engineering
- 일반주제명
- Biochemistry
- 일반주제명
- Nanoscience
- 키워드
- Monocytes
- 키워드
- Nanoparticles
- 키워드
- Shear Stress
- 키워드
- Uptake
- 기타저자
- Carnegie Mellon University Chemical Engineering
- 기본자료저록
- Dissertations Abstracts International. 85-11B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798382342320
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■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a660
■1001 ▼aAldarondo, Dasia A.▼0(orcid)0000-0003-4239-7467
■24510▼aShear Stress-Induced Phenotypic Alterations in Monocytes: Exploring Rheometer Shear and ACE2 Dysregulation Effects
■260 ▼a[Sl]▼bCarnegie Mellon University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a84 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-11, Section: B.
■500 ▼aAdvisor: Wayne, Elizabeth C.
■5021 ▼aThesis (Ph.D.)--Carnegie Mellon University, 2024.
■520 ▼aDue to the increasing population of individuals with cardiovascular diseases and related comorbidities, there is a growing need for the development of synergistic therapeutics. Monocytes are implicated in a broad spectrum of diseases and can serve as a focal point for therapeutic targeting. Monocytes are members of the mononuclear phagocyte system involved in pathogen clearance and nanoparticle pharmacokinetics. Monocytes play a critical role in the development and progression of cardiovascular diseases. While studies have investigated the effect of nanoparticle modulation on monocyte uptake, their physiological responses to the shears associated with cardiovascular diseases have not been largely studied. In this thesis, we set out to determine the effect of shear on monocytes in varying physiological and mechanical models. The impact of ACE2 deficiency was explicitly investigated in the monocyte's ability to uptake nanoparticles.Moreover, we investigated nanoparticle uptake as a function of nanoparticle size, physiological shear stress, and monocyte ACE2 expression. Higher shear stress exposure increased nanoparticle uptake in ACE2- cells but not in wild-type cells. In addition, the shear stress and nanoparticle uptake appeared to downregulate gene expression more dramatically in ACE2- cells. Our data demonstrates that ACE2- cells exhibit different sensitivities to the same nanoparticle systems. Observing how nanoparticles can modulate monocytes in the context of disease can inform precision dosing. This work demonstrates the benefits of adding more physiologically relevant conditions to in vitro cultures to better inform disease studies, specifically in cardiovascular diseases.
■590 ▼aSchool code: 0041.
■650 4▼aChemical engineering
■650 4▼aBiochemistry
■650 4▼aNanoscience
■653 ▼aCardiovascular diseases
■653 ▼aMonocytes
■653 ▼aNanoparticles
■653 ▼aShear Stress
■653 ▼aUptake
■690 ▼a0542
■690 ▼a0565
■690 ▼a0487
■71020▼aCarnegie Mellon University▼bChemical Engineering.
■7730 ▼tDissertations Abstracts International▼g85-11B.
■790 ▼a0041
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17161428▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
