No Cover Image

E-Thesis 215 views

Analysis of Mechanisms Involved in Ventricular Assist Device (VAD) Induced Extracellular Vesicle Generation and their Cellular Effects / REBECCA JAMES

Swansea University Author: REBECCA JAMES

  • E-Thesis – open access under embargo until: 17th August 2027

DOI (Published version): 10.23889/SUthesis.60859

Abstract

Heart failure is a major global health issue, carrying a significant risk of morbidity and mortality. The current gold standard treatment for end-stage heart failure is heart transplantation. However, with reduced availability of viable organs, and a non-sustainable treatment strategy, alternate mec...

Full description

Published: Swansea 2022
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
Supervisor: Kanamarlapudi, Venkateswarlu
URI: https://cronfa.swan.ac.uk/Record/cronfa60859
Tags: Add Tag
No Tags, Be the first to tag this record!
first_indexed 2022-08-19T15:42:39Z
last_indexed 2023-01-13T19:21:18Z
id cronfa60859
recordtype RisThesis
fullrecord <?xml version="1.0"?><rfc1807><datestamp>2022-08-19T16:50:21.5797659</datestamp><bib-version>v2</bib-version><id>60859</id><entry>2022-08-19</entry><title>Analysis of Mechanisms Involved in Ventricular Assist Device (VAD) Induced Extracellular Vesicle Generation and their Cellular Effects</title><swanseaauthors><author><sid>0fbbb4f56f2ec22af404f2c182949bf8</sid><firstname>REBECCA</firstname><surname>JAMES</surname><name>REBECCA JAMES</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2022-08-19</date><abstract>Heart failure is a major global health issue, carrying a significant risk of morbidity and mortality. The current gold standard treatment for end-stage heart failure is heart transplantation. However, with reduced availability of viable organs, and a non-sustainable treatment strategy, alternate mechanisms are being sought to prolong life. Ventricular assist devices (VADs) offer a potential life-extending treatment, however, do not come without adverse events. Therefore, it is vital to understand and reduce these side effects in order to maximise patient quality of life. More recently, extracellular vesicles (EVs) have increased in popularity amongst various scientific disciplines. EVs are small (&lt;1000 nanometre) membrane-bound packages secreted from all cell types, which are known to have roles in both health and disease. However, there is limited knowledge into the roles of EVs in VAD patients. Therefore, this study investigated the prevalence, origin and roles of EVs concerning VADs. One significant challenge facing EV research is the isolation and detection of EVs, which increases in complexity when assessing EVs in biological fluids that contain numerous components. This study began by assessing the most commonly used isolation and detection techniques and tested their applicability to blood plasma, with mixed results. We demonstrated the need for diluting higher viscosity fluids prior to EV extraction. Secondly, this study displayed the increased prevalence of EVs produced by both leukocytes and platelets exposed to elevated levels of non-physiological shear stress both in vitro and in vivo. We display the effect of VADs as a perpetuating factor in EV production and demonstrated the potential use of EVs as a means of diagnostics in adverse events, to aid in mitigating VAD patient outcomes. Finally, we presented the detrimental effects of elevated pathological EVs in patient prognosis. We assessed cargo alterations within EVs present in both healthy and pathological blood and determined downstream effects. Here, increased levels of leukocyte and platelet EVs are shown to have the potential to induce inflammation and cellular activation. Conversely, we also revealed the therapeutic and disease mitigating potentials of healthy EVs. In conclusion, this study has provided a consensus on the protocol for EV isolation from plasma and a platform for EV research in relation to heart failure and VAD patients. Furthermore, we show VAD shear stress as a significant instigator of EV release. Subsequently, we demonstrate the possibility of healthy EVs in limiting pathological processes. Therefore, this research successfully highlighted the significant impacts of EVs in VAD patients, which can be utilised to improve patient outcomes.</abstract><type>E-Thesis</type><journal/><volume/><journalNumber/><paginationStart/><paginationEnd/><publisher/><placeOfPublication>Swansea</placeOfPublication><isbnPrint/><isbnElectronic/><issnPrint/><issnElectronic/><keywords/><publishedDay>17</publishedDay><publishedMonth>8</publishedMonth><publishedYear>2022</publishedYear><publishedDate>2022-08-17</publishedDate><doi>10.23889/SUthesis.60859</doi><url/><notes/><college>COLLEGE NANME</college><CollegeCode>COLLEGE CODE</CollegeCode><institution>Swansea University</institution><supervisor>Kanamarlapudi, Venkateswarlu</supervisor><degreelevel>Doctoral</degreelevel><degreename>Ph.D</degreename><degreesponsorsfunders>KESS</degreesponsorsfunders><apcterm/><funders/><projectreference/><lastEdited>2022-08-19T16:50:21.5797659</lastEdited><Created>2022-08-19T16:39:05.1562528</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Medicine</level></path><authors><author><firstname>REBECCA</firstname><surname>JAMES</surname><order>1</order></author></authors><documents><document><filename>Under embargo</filename><originalFilename>Under embargo</originalFilename><uploaded>2022-08-19T16:48:37.6857129</uploaded><type>Output</type><contentLength>11223184</contentLength><contentType>application/pdf</contentType><version>E-Thesis &#x2013; open access</version><cronfaStatus>true</cronfaStatus><embargoDate>2027-08-17T00:00:00.0000000</embargoDate><documentNotes>Copyright: The author, Rebecca L. James, 2022.</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language></document></documents><OutputDurs/></rfc1807>
spelling 2022-08-19T16:50:21.5797659 v2 60859 2022-08-19 Analysis of Mechanisms Involved in Ventricular Assist Device (VAD) Induced Extracellular Vesicle Generation and their Cellular Effects 0fbbb4f56f2ec22af404f2c182949bf8 REBECCA JAMES REBECCA JAMES true false 2022-08-19 Heart failure is a major global health issue, carrying a significant risk of morbidity and mortality. The current gold standard treatment for end-stage heart failure is heart transplantation. However, with reduced availability of viable organs, and a non-sustainable treatment strategy, alternate mechanisms are being sought to prolong life. Ventricular assist devices (VADs) offer a potential life-extending treatment, however, do not come without adverse events. Therefore, it is vital to understand and reduce these side effects in order to maximise patient quality of life. More recently, extracellular vesicles (EVs) have increased in popularity amongst various scientific disciplines. EVs are small (<1000 nanometre) membrane-bound packages secreted from all cell types, which are known to have roles in both health and disease. However, there is limited knowledge into the roles of EVs in VAD patients. Therefore, this study investigated the prevalence, origin and roles of EVs concerning VADs. One significant challenge facing EV research is the isolation and detection of EVs, which increases in complexity when assessing EVs in biological fluids that contain numerous components. This study began by assessing the most commonly used isolation and detection techniques and tested their applicability to blood plasma, with mixed results. We demonstrated the need for diluting higher viscosity fluids prior to EV extraction. Secondly, this study displayed the increased prevalence of EVs produced by both leukocytes and platelets exposed to elevated levels of non-physiological shear stress both in vitro and in vivo. We display the effect of VADs as a perpetuating factor in EV production and demonstrated the potential use of EVs as a means of diagnostics in adverse events, to aid in mitigating VAD patient outcomes. Finally, we presented the detrimental effects of elevated pathological EVs in patient prognosis. We assessed cargo alterations within EVs present in both healthy and pathological blood and determined downstream effects. Here, increased levels of leukocyte and platelet EVs are shown to have the potential to induce inflammation and cellular activation. Conversely, we also revealed the therapeutic and disease mitigating potentials of healthy EVs. In conclusion, this study has provided a consensus on the protocol for EV isolation from plasma and a platform for EV research in relation to heart failure and VAD patients. Furthermore, we show VAD shear stress as a significant instigator of EV release. Subsequently, we demonstrate the possibility of healthy EVs in limiting pathological processes. Therefore, this research successfully highlighted the significant impacts of EVs in VAD patients, which can be utilised to improve patient outcomes. E-Thesis Swansea 17 8 2022 2022-08-17 10.23889/SUthesis.60859 COLLEGE NANME COLLEGE CODE Swansea University Kanamarlapudi, Venkateswarlu Doctoral Ph.D KESS 2022-08-19T16:50:21.5797659 2022-08-19T16:39:05.1562528 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine REBECCA JAMES 1 Under embargo Under embargo 2022-08-19T16:48:37.6857129 Output 11223184 application/pdf E-Thesis – open access true 2027-08-17T00:00:00.0000000 Copyright: The author, Rebecca L. James, 2022. true eng
title Analysis of Mechanisms Involved in Ventricular Assist Device (VAD) Induced Extracellular Vesicle Generation and their Cellular Effects
spellingShingle Analysis of Mechanisms Involved in Ventricular Assist Device (VAD) Induced Extracellular Vesicle Generation and their Cellular Effects
REBECCA JAMES
title_short Analysis of Mechanisms Involved in Ventricular Assist Device (VAD) Induced Extracellular Vesicle Generation and their Cellular Effects
title_full Analysis of Mechanisms Involved in Ventricular Assist Device (VAD) Induced Extracellular Vesicle Generation and their Cellular Effects
title_fullStr Analysis of Mechanisms Involved in Ventricular Assist Device (VAD) Induced Extracellular Vesicle Generation and their Cellular Effects
title_full_unstemmed Analysis of Mechanisms Involved in Ventricular Assist Device (VAD) Induced Extracellular Vesicle Generation and their Cellular Effects
title_sort Analysis of Mechanisms Involved in Ventricular Assist Device (VAD) Induced Extracellular Vesicle Generation and their Cellular Effects
author_id_str_mv 0fbbb4f56f2ec22af404f2c182949bf8
author_id_fullname_str_mv 0fbbb4f56f2ec22af404f2c182949bf8_***_REBECCA JAMES
author REBECCA JAMES
author2 REBECCA JAMES
format E-Thesis
publishDate 2022
institution Swansea University
doi_str_mv 10.23889/SUthesis.60859
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 0
active_str 0
description Heart failure is a major global health issue, carrying a significant risk of morbidity and mortality. The current gold standard treatment for end-stage heart failure is heart transplantation. However, with reduced availability of viable organs, and a non-sustainable treatment strategy, alternate mechanisms are being sought to prolong life. Ventricular assist devices (VADs) offer a potential life-extending treatment, however, do not come without adverse events. Therefore, it is vital to understand and reduce these side effects in order to maximise patient quality of life. More recently, extracellular vesicles (EVs) have increased in popularity amongst various scientific disciplines. EVs are small (<1000 nanometre) membrane-bound packages secreted from all cell types, which are known to have roles in both health and disease. However, there is limited knowledge into the roles of EVs in VAD patients. Therefore, this study investigated the prevalence, origin and roles of EVs concerning VADs. One significant challenge facing EV research is the isolation and detection of EVs, which increases in complexity when assessing EVs in biological fluids that contain numerous components. This study began by assessing the most commonly used isolation and detection techniques and tested their applicability to blood plasma, with mixed results. We demonstrated the need for diluting higher viscosity fluids prior to EV extraction. Secondly, this study displayed the increased prevalence of EVs produced by both leukocytes and platelets exposed to elevated levels of non-physiological shear stress both in vitro and in vivo. We display the effect of VADs as a perpetuating factor in EV production and demonstrated the potential use of EVs as a means of diagnostics in adverse events, to aid in mitigating VAD patient outcomes. Finally, we presented the detrimental effects of elevated pathological EVs in patient prognosis. We assessed cargo alterations within EVs present in both healthy and pathological blood and determined downstream effects. Here, increased levels of leukocyte and platelet EVs are shown to have the potential to induce inflammation and cellular activation. Conversely, we also revealed the therapeutic and disease mitigating potentials of healthy EVs. In conclusion, this study has provided a consensus on the protocol for EV isolation from plasma and a platform for EV research in relation to heart failure and VAD patients. Furthermore, we show VAD shear stress as a significant instigator of EV release. Subsequently, we demonstrate the possibility of healthy EVs in limiting pathological processes. Therefore, this research successfully highlighted the significant impacts of EVs in VAD patients, which can be utilised to improve patient outcomes.
published_date 2022-08-17T04:19:19Z
_version_ 1763754282625007616
score 11.013148

Similar Items