Material Type  

 학위논문

 

0017161428

Date and Time of Latest Transaction  

20250211151355

ISBN  

9798382342320

DDC  

660

Author  

Aldarondo, Dasia A.

Title/Author  

Shear Stress-Induced Phenotypic Alterations in Monocytes: Exploring Rheometer Shear and ACE2 Dysregulation Effects.

Publish Info  

[S.l.] : Carnegie Mellon University., 2024

Publish Info  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Material Info  

84 p.

General Note  

Source: Dissertations Abstracts International, Volume: 85-11, Section: B.

General Note  

Advisor: Wayne, Elizabeth C.

학위논문주기  

Thesis (Ph.D.)--Carnegie Mellon University, 2024.

Abstracts/Etc  

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.

Subject Added Entry-Topical Term  

Chemical engineering.

Subject Added Entry-Topical Term  

Biochemistry.

Subject Added Entry-Topical Term  

Nanoscience.

Index Term-Uncontrolled  

Cardiovascular diseases

Index Term-Uncontrolled  

Monocytes

Index Term-Uncontrolled  

Nanoparticles

Index Term-Uncontrolled  

Shear Stress

Index Term-Uncontrolled  

Uptake

Added Entry-Corporate Name  

Carnegie Mellon University Chemical Engineering

Host Item Entry  

Dissertations Abstracts International. 85-11B.

Electronic Location and Access  

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Control Number  

joongbu:658300