자료유형  

 학위논문

Control Number  

0016932994

International Standard Book Number  

9798380388528

Dewey Decimal Classification Number  

574

Main Entry-Personal Name  

Liu, Yue.

Publication, Distribution, etc. (Imprint  

[S.l.] : University of Pennsylvania., 2023

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2023

Physical Description  

1 online resource(71 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 85-03, Section: B.

General Note  

Advisor: Diamond, Scott L.

Dissertation Note  

Thesis (Ph.D.)--University of Pennsylvania, 2023.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약Previously, studies on cardiovascular biology in vitro were predominantly conducted using static assays with plasma or isolated blood cells. However, microfluidic technologies present a distinctive opportunity to investigate the mechanisms of hemostasis and thrombosis in conditions that mimic physiological settings. This thesis outlines the utilization of a microfluidic method to simulate cardiovascular ailments and assess potential treatments. In our studies, platelet deposition on collagen was measured using thrombin-inhibited anticoagulated treated whole blood with various TLR agonists. It was observed that most of the tested TLR agonists reduced platelet deposition, except for TLR4 agonist LPS which increased deposition. TLR-7 agonists caused an immediate blockade of platelet deposition. Inhibitors of the IKK/NF-ΚB pathway also strongly inhibited platelet deposition under flow. Addition of Pam3CSK4 (TLR1/2 ligand), MALP-2 (TLR2/6 ligand) and Imquimod (TLR7 ligand) reduced phosphotidylserine (PS) exposure. Activation of TLR1/2, TLR2/6, TLR3, TLR7, TLR9 in whole blood reduced platelet deposition under flow on collagen, however LPS activation of TLR4 was clearly pro-thrombotic. We also used our microfluidic clotting assays to monitor Factor XIIIa activity and fibrin in whole blood clots forming under flow. We tested a fluorescent peptide derived from alpha-2 antiplasmin sequence to monitor the location of transglutaminase activity and fibrin during whole blood clotting under microfluidic flow. The peptide rapidly appeared in the same location as accumulating fibrin, as expected for a transglutaminase activity bound to fibrin. The thrombin inhibitor PPACK ablated fibrin generation and concomitant peptide labeling of fibrin. The FXIIIa inhibitor T101 had no effect on fibrin generation but ablated the labeling of fibrin by the peptide. Similarly, Gly-Pro-Arg-Pro abated fibrin formation and thus strongly attenuated the peptide signal. At arterial wall shear rate, less fibrin was formed and consequently less peptide labeling of fibrin was detected as compared to venous conditions. Addition of tissue plasminogen activator caused a reduction of both fibrin and peptide signal. Also, the peptide strongly colocalized with fibrin in clots from laser-injured mouse cremaster arterioles. The synthetic peptide provided a strong and sustained labeling of fibrin as it formed under flow.

Subject Added Entry-Topical Term  

Molecular biology.

Subject Added Entry-Topical Term  

Biochemistry.

Subject Added Entry-Topical Term  

Bioengineering.

Index Term-Uncontrolled  

FXIIIa

Index Term-Uncontrolled  

Hemostasis

Index Term-Uncontrolled  

Microfluidic technologies

Index Term-Uncontrolled  

Thrombosis

Index Term-Uncontrolled  

Toll-like receptors

Index Term-Uncontrolled  

Phosphotidylserine

Index Term-Uncontrolled  

Fibrin

Added Entry-Corporate Name  

University of Pennsylvania Chemical and Biomolecular Engineering

Host Item Entry  

Dissertations Abstracts International. 85-03B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:644082