{"id":{"repo_id":"toronto-retro","oai_identifier":"oai:utoronto.scholaris.ca:1807/93024"},"canonical_url":"https://search.dev.ndltd.org/etd/toronto-retro/oai:utoronto.scholaris.ca:1807/93024","repository":{"repo_id":"toronto-retro","name":"University of Toronto","base_url":"https://utoronto.scholaris.ca/server/oai/request"},"display":{"title":"The Role of Autophagy in the Pathogenesis and Clinical Course of Abdominal Aortic Aneurysms","abstract":"Abdominal aortic aneurysm (AAA) is a permanent progressive focal dilation of the aorta that is â Ľ 50% of the normal aortic diameter, due to loss of wall structural integrity. A fatal outcome of the progressive dilation due to the compromised aortic wall integrity is rupture. Mortality associated with rupture is ~88%. While the histopathological characteristics of AAA are well documented, cellular and molecular mechanisms involved in AAA pathogenesis are not entirely understood. Autophagy is a conserved housekeeping basal cellular process for the turnover of organelles and proteins that occur in all eukaryotic cells. It can also be activated as an adaptive response to stressful and pathological conditions to promote cell survival. However, contrary to the classical autophagy pro-survival role, in some circumstances, autophagy can lead to cellular demise. Increasing evidence suggests that autophagy perturbation is associated with the development of multiple age-related and chronic disorders. Also, preclinical studies have identified autophagy as a process that is activated in cardiovascular diseases such as atherosclerosis, which share several pathological features to AAA. Importantly, emerging evidence suggest that vascular cell autophagy is a reparative and protective process in atherosclerosis pathogenesis. While several autophagy-related genes were found to be upregulated in human aneurysmal tissue, the role of autophagy in AAA pathogenesis remains undefined. My research aim was to evaluate the potential role of autophagy in the development, progression and rupture of AAA. To achieve this, we initially sought to define autophagy gene expression in an experimental mouse model of AAA. Then to elucidate the functional role of autophagy in AAA evolution, we utilized both global and cell-specific loss of functional approaches. Our study demonstrated that autophagy was activated in the Ang II-infused ApoE-/- AAA mouse model. Global loss of functional approach via systemic administration of the autophagy inhibitor chloroquine (CQ) did not alter the development, progression or rupture of AAA in mice. However, smooth muscle specific (SMC) ATG7 deficiency enhanced the susceptibility to AAA formation evident by the formation of pre-aneurysmal changes, emphasizing the significance of intact SMC autophagy in impeding the development of pre- aneurysmal changes that otherwise may lead to AAA development.","abstract_html":"Abdominal aortic aneurysm (AAA) is a permanent progressive focal dilation of the aorta that is â Ľ 50% of the normal aortic diameter, due to loss of wall structural integrity. A fatal outcome of the progressive dilation due to the compromised aortic wall integrity is rupture. Mortality associated with rupture is ~88%. While the histopathological characteristics of AAA are well documented, cellular and molecular mechanisms involved in AAA pathogenesis are not entirely understood. Autophagy is a conserved housekeeping basal cellular process for the turnover of organelles and proteins that occur in all eukaryotic cells. It can also be activated as an adaptive response to stressful and pathological conditions to promote cell survival. However, contrary to the classical autophagy pro-survival role, in some circumstances, autophagy can lead to cellular demise. Increasing evidence suggests that autophagy perturbation is associated with the development of multiple age-related and chronic disorders. Also, preclinical studies have identified autophagy as a process that is activated in cardiovascular diseases such as atherosclerosis, which share several pathological features to AAA. Importantly, emerging evidence suggest that vascular cell autophagy is a reparative and protective process in atherosclerosis pathogenesis. While several autophagy-related genes were found to be upregulated in human aneurysmal tissue, the role of autophagy in AAA pathogenesis remains undefined. My research aim was to evaluate the potential role of autophagy in the development, progression and rupture of AAA. To achieve this, we initially sought to define autophagy gene expression in an experimental mouse model of AAA. Then to elucidate the functional role of autophagy in AAA evolution, we utilized both global and cell-specific loss of functional approaches. Our study demonstrated that autophagy was activated in the Ang II-infused ApoE-/- AAA mouse model. Global loss of functional approach via systemic administration of the autophagy inhibitor chloroquine (CQ) did not alter the development, progression or rupture of AAA in mice. However, smooth muscle specific (SMC) ATG7 deficiency enhanced the susceptibility to AAA formation evident by the formation of pre-aneurysmal changes, emphasizing the significance of intact SMC autophagy in impeding the development of pre- aneurysmal changes that otherwise may lead to AAA development.","abstract_has_math":false,"creators":["Ramadan, Azza"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":"Medical Science","school":null,"contributors":[],"advisors":["Verma, Subodh"],"committee_chairs":[],"committee_members":[],"year":2017,"date_issued":"2017-11","date_published":"2017-11","updated_at":"2026-07-27T21:28:16Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1807/93024","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Verma, Subodh"]},{"key":"dc:contributor.department","label":"Department","values":["Medical Science"]},{"key":"dc:creator","label":"Author","values":["Ramadan, Azza"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2017-11"]},{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2018-12-19T05:00:15Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2018-12-19T05:00:15Z"]},{"key":"dc:date.issued","label":"Date","values":["2017-11"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1807/93024"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Abdominal aortic aneurysm (AAA) is a permanent progressive focal dilation of the aorta that is â Ľ 50% of the normal aortic diameter, due to loss of wall structural integrity. A fatal outcome of the progressive dilation due to the compromised aortic wall integrity is rupture. Mortality associated with rupture is ~88%. While the histopathological characteristics of AAA are well documented, cellular and molecular mechanisms involved in AAA pathogenesis are not entirely understood. Autophagy is a conserved housekeeping basal cellular process for the turnover of organelles and proteins that occur in all eukaryotic cells. It can also be activated as an adaptive response to stressful and pathological conditions to promote cell survival. However, contrary to the classical autophagy pro-survival role, in some circumstances, autophagy can lead to cellular demise. Increasing evidence suggests that autophagy perturbation is associated with the development of multiple age-related and chronic disorders. Also, preclinical studies have identified autophagy as a process that is activated in cardiovascular diseases such as atherosclerosis, which share several pathological features to AAA. Importantly, emerging evidence suggest that vascular cell autophagy is a reparative and protective process in atherosclerosis pathogenesis. While several autophagy-related genes were found to be upregulated in human aneurysmal tissue, the role of autophagy in AAA pathogenesis remains undefined. My research aim was to evaluate the potential role of autophagy in the development, progression and rupture of AAA. To achieve this, we initially sought to define autophagy gene expression in an experimental mouse model of AAA. Then to elucidate the functional role of autophagy in AAA evolution, we utilized both global and cell-specific loss of functional approaches. Our study demonstrated that autophagy was activated in the Ang II-infused ApoE-/- AAA mouse model. Global loss of functional approach via systemic administration of the autophagy inhibitor chloroquine (CQ) did not alter the development, progression or rupture of AAA in mice. However, smooth muscle specific (SMC) ATG7 deficiency enhanced the susceptibility to AAA formation evident by the formation of pre-aneurysmal changes, emphasizing the significance of intact SMC autophagy in impeding the development of pre- aneurysmal changes that otherwise may lead to AAA development."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph.D."]},{"key":"dc:title","label":"Title","values":["The Role of Autophagy in the Pathogenesis and Clinical Course of Abdominal Aortic Aneurysms"]}]}],"canonical_facts":{"dc:contributor.advisor":["Verma, Subodh"],"dc:contributor.department":["Medical Science"],"dc:creator":["Ramadan, Azza"],"dc:date":["2017-11"],"dc:date.accessioned":["2018-12-19T05:00:15Z"],"dc:date.available":["2018-12-19T05:00:15Z"],"dc:date.issued":["2017-11"],"dc:description.abstract":["Abdominal aortic aneurysm (AAA) is a permanent progressive focal dilation of the aorta that is â Ľ 50% of the normal aortic diameter, due to loss of wall structural integrity. A fatal outcome of the progressive dilation due to the compromised aortic wall integrity is rupture. Mortality associated with rupture is ~88%. While the histopathological characteristics of AAA are well documented, cellular and molecular mechanisms involved in AAA pathogenesis are not entirely understood. Autophagy is a conserved housekeeping basal cellular process for the turnover of organelles and proteins that occur in all eukaryotic cells. It can also be activated as an adaptive response to stressful and pathological conditions to promote cell survival. However, contrary to the classical autophagy pro-survival role, in some circumstances, autophagy can lead to cellular demise. Increasing evidence suggests that autophagy perturbation is associated with the development of multiple age-related and chronic disorders. Also, preclinical studies have identified autophagy as a process that is activated in cardiovascular diseases such as atherosclerosis, which share several pathological features to AAA. Importantly, emerging evidence suggest that vascular cell autophagy is a reparative and protective process in atherosclerosis pathogenesis. While several autophagy-related genes were found to be upregulated in human aneurysmal tissue, the role of autophagy in AAA pathogenesis remains undefined. My research aim was to evaluate the potential role of autophagy in the development, progression and rupture of AAA. To achieve this, we initially sought to define autophagy gene expression in an experimental mouse model of AAA. Then to elucidate the functional role of autophagy in AAA evolution, we utilized both global and cell-specific loss of functional approaches. Our study demonstrated that autophagy was activated in the Ang II-infused ApoE-/- AAA mouse model. Global loss of functional approach via systemic administration of the autophagy inhibitor chloroquine (CQ) did not alter the development, progression or rupture of AAA in mice. However, smooth muscle specific (SMC) ATG7 deficiency enhanced the susceptibility to AAA formation evident by the formation of pre-aneurysmal changes, emphasizing the significance of intact SMC autophagy in impeding the development of pre- aneurysmal changes that otherwise may lead to AAA development."],"dc:description.degree":["Ph.D."],"dc:identifier.uri":["http://hdl.handle.net/1807/93024"],"dc:title":["The Role of Autophagy in the Pathogenesis and Clinical Course of Abdominal Aortic Aneurysms"],"dc:type":["Thesis"]},"updated_at":"2026-07-27T21:28:16Z"}