{"id":{"repo_id":"utmb","oai_identifier":"oai:utmb-ir.tdl.org:2152.3/828"},"canonical_url":"https://search.dev.ndltd.org/etd/utmb/oai:utmb-ir.tdl.org:2152.3/828","repository":{"repo_id":"utmb","name":"University of Texas Medical Branch","base_url":"https://utmb-ir.tdl.org/server/oai/request"},"display":{"title":"The Role of IL-6 in Inflammatory Aortic Aneurysmal Diseases","abstract":"Interleukin-6 (IL-6), a member of a superfamily of cardioactive cytokines, has been identified as an independent biomarker of vascular diseases including atherosclerosis and aortic aneurysms. Local vascular IL-6 secretion can be induced by dysregulated angiotensin II (Ang II) signaling, producing leukocyte infiltration that results in life-threatening aortic aneurysms and dissections. Precise mechanisms by which IL-6 signaling induces leukocyte recruitment remain unknown. In this study, we employed two experimental animal models to study the role of IL-6 activation in the development and progression of aortic aneurysms. In an Ang II-treated C57BL/6 mice model, we tested the relationship of IL-6 signaling with Th17-induced inflammation in the formation of Ang II-induced aortic dissections. We found that Ang II infusion induced aortic dissections and CD4+-interleukin 17A (IL-17A)-expressing, Th17 cell accumulation in C57BL/6 mice. IL-6-deficient mice showed blunted local Th17 activation, macrophage recruitment, and reduced incidence of aortic dissections, suggesting the importance of IL-6 signaling in inducing Th17-mediated aneurysmal progression. We further showed the pathological roles of Th17 lymphocytes by depleting Th17 by IL-17A neutralization or genetic mutation and showed decreased aortic chemokine MCP-1 production and macrophage recruitment, leading to a reduction in aortic dissections. We also established clinical relevance by showing increased Th17 infiltration into the aortic adventitial-medial border in patients with ascending aortic dissections. These findings indicate that IL-6 signaling converges on Th17 recruitment and IL-17A signaling upstream of macrophage recruitment, mediating vascular inflammation and aortic dissections. In another mouse model with spontaneous aortic aneurysms due to Marfan Syndrome (MFS) caused by Fbn-1 gene mutation (mgR homozygotes), we also reported elevated IL-6 signaling and increased macrophage recruitment in ascending aneurysmal tissues. To study the role of IL-6 signaling, we generated mgR homozygotes with IL-6 deficiency (DKOs), which showed reduction in aneurysmal dilation at late stage of disease with unaffected survival rate. Moreover, we reported that IL-6 deficiency led to decreased ECM degradation that is associated with reduced levels of local MMPs. These findings suggests the activation of IL-6-mediated inflammatory signaling contributed to aneurysmal progression in MFS through recruitment of leukocytes and stimulation of MMP expression, thus aggravating ECM degradation and vascular remodeling.","abstract_html":"Interleukin-6 (IL-6), a member of a superfamily of cardioactive cytokines, has been identified as an independent biomarker of vascular diseases including atherosclerosis and aortic aneurysms. Local vascular IL-6 secretion can be induced by dysregulated angiotensin II (Ang II) signaling, producing leukocyte infiltration that results in life-threatening aortic aneurysms and dissections. Precise mechanisms by which IL-6 signaling induces leukocyte recruitment remain unknown. In this study, we employed two experimental animal models to study the role of IL-6 activation in the development and progression of aortic aneurysms. In an Ang II-treated C57BL/6 mice model, we tested the relationship of IL-6 signaling with Th17-induced inflammation in the formation of Ang II-induced aortic dissections. We found that Ang II infusion induced aortic dissections and CD4+-interleukin 17A (IL-17A)-expressing, Th17 cell accumulation in C57BL/6 mice. IL-6-deficient mice showed blunted local Th17 activation, macrophage recruitment, and reduced incidence of aortic dissections, suggesting the importance of IL-6 signaling in inducing Th17-mediated aneurysmal progression. We further showed the pathological roles of Th17 lymphocytes by depleting Th17 by IL-17A neutralization or genetic mutation and showed decreased aortic chemokine MCP-1 production and macrophage recruitment, leading to a reduction in aortic dissections. We also established clinical relevance by showing increased Th17 infiltration into the aortic adventitial-medial border in patients with ascending aortic dissections. These findings indicate that IL-6 signaling converges on Th17 recruitment and IL-17A signaling upstream of macrophage recruitment, mediating vascular inflammation and aortic dissections. In another mouse model with spontaneous aortic aneurysms due to Marfan Syndrome (MFS) caused by Fbn-1 gene mutation (mgR homozygotes), we also reported elevated IL-6 signaling and increased macrophage recruitment in ascending aneurysmal tissues. To study the role of IL-6 signaling, we generated mgR homozygotes with IL-6 deficiency (DKOs), which showed reduction in aneurysmal dilation at late stage of disease with unaffected survival rate. Moreover, we reported that IL-6 deficiency led to decreased ECM degradation that is associated with reduced levels of local MMPs. These findings suggests the activation of IL-6-mediated inflammatory signaling contributed to aneurysmal progression in MFS through recruitment of leukocytes and stimulation of MMP expression, thus aggravating ECM degradation and vascular remodeling.","abstract_has_math":false,"creators":["Ju, Xiaoxi 1984-"],"institution":"The University of Texas Medical Branch at Galveston","degree_name":"Biochemistry and Molecular Biology (Doctoral)","degree_level":"Doctoral","degree_discipline":"Cell Biology and Molecular Biology","degree_department":null,"school":null,"contributors":[],"advisors":["Fujise, Ken"],"committee_chairs":[],"committee_members":["Brasier, Allan R","Tilton, Ronald G","Milewicz, Dianna M","Vargas, Gracie","Wakamiya, Maki"],"year":null,"date_issued":"","date_published":null,"updated_at":"2026-07-24T05:50:51Z","subjects":["Interleukin-6","Aortic aneurysms","Aortic dissections","Angiotensin II","Th17","marfan syndrome"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2152.3/828","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Fujise, Ken"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Brasier, Allan R","Tilton, Ronald G","Milewicz, Dianna M","Vargas, Gracie","Wakamiya, Maki"]},{"key":"dc:creator","label":"Author","values":["Ju, Xiaoxi 1984-"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2016-11-14T15:22:55Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2016-11-14T15:22:55Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Cell Biology and Molecular Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Biochemistry and Molecular Biology (Doctoral)"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Texas Medical Branch at Galveston"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Interleukin-6","Aortic aneurysms","Aortic dissections","Angiotensin II","Th17","marfan syndrome"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/2152.3/828"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Interleukin-6 (IL-6), a member of a superfamily of cardioactive cytokines, has been identified as an independent biomarker of vascular diseases including atherosclerosis and aortic aneurysms. Local vascular IL-6 secretion can be induced by dysregulated angiotensin II (Ang II) signaling, producing leukocyte infiltration that results in life-threatening aortic aneurysms and dissections. Precise mechanisms by which IL-6 signaling induces leukocyte recruitment remain unknown. In this study, we employed two experimental animal models to study the role of IL-6 activation in the development and progression of aortic aneurysms. In an Ang II-treated C57BL/6 mice model, we tested the relationship of IL-6 signaling with Th17-induced inflammation in the formation of Ang II-induced aortic dissections. We found that Ang II infusion induced aortic dissections and CD4+-interleukin 17A (IL-17A)-expressing, Th17 cell accumulation in C57BL/6 mice. IL-6-deficient mice showed blunted local Th17 activation, macrophage recruitment, and reduced incidence of aortic dissections, suggesting the importance of IL-6 signaling in inducing Th17-mediated aneurysmal progression. We further showed the pathological roles of Th17 lymphocytes by depleting Th17 by IL-17A neutralization or genetic mutation and showed decreased aortic chemokine MCP-1 production and macrophage recruitment, leading to a reduction in aortic dissections. We also established clinical relevance by showing increased Th17 infiltration into the aortic adventitial-medial border in patients with ascending aortic dissections. These findings indicate that IL-6 signaling converges on Th17 recruitment and IL-17A signaling upstream of macrophage recruitment, mediating vascular inflammation and aortic dissections. In another mouse model with spontaneous aortic aneurysms due to Marfan Syndrome (MFS) caused by Fbn-1 gene mutation (mgR homozygotes), we also reported elevated IL-6 signaling and increased macrophage recruitment in ascending aneurysmal tissues. To study the role of IL-6 signaling, we generated mgR homozygotes with IL-6 deficiency (DKOs), which showed reduction in aneurysmal dilation at late stage of disease with unaffected survival rate. Moreover, we reported that IL-6 deficiency led to decreased ECM degradation that is associated with reduced levels of local MMPs. These findings suggests the activation of IL-6-mediated inflammatory signaling contributed to aneurysmal progression in MFS through recruitment of leukocytes and stimulation of MMP expression, thus aggravating ECM degradation and vascular remodeling."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["The Role of IL-6 in Inflammatory Aortic Aneurysmal Diseases"]}]}],"canonical_facts":{"dc:contributor.advisor":["Fujise, Ken"],"dc:contributor.committeemember":["Brasier, Allan R","Tilton, Ronald G","Milewicz, Dianna M","Vargas, Gracie","Wakamiya, Maki"],"dc:creator":["Ju, Xiaoxi 1984-"],"dc:date.accessioned":["2016-11-14T15:22:55Z"],"dc:date.available":["2016-11-14T15:22:55Z"],"dc:description.abstract":["Interleukin-6 (IL-6), a member of a superfamily of cardioactive cytokines, has been identified as an independent biomarker of vascular diseases including atherosclerosis and aortic aneurysms. Local vascular IL-6 secretion can be induced by dysregulated angiotensin II (Ang II) signaling, producing leukocyte infiltration that results in life-threatening aortic aneurysms and dissections. Precise mechanisms by which IL-6 signaling induces leukocyte recruitment remain unknown. In this study, we employed two experimental animal models to study the role of IL-6 activation in the development and progression of aortic aneurysms. In an Ang II-treated C57BL/6 mice model, we tested the relationship of IL-6 signaling with Th17-induced inflammation in the formation of Ang II-induced aortic dissections. We found that Ang II infusion induced aortic dissections and CD4+-interleukin 17A (IL-17A)-expressing, Th17 cell accumulation in C57BL/6 mice. IL-6-deficient mice showed blunted local Th17 activation, macrophage recruitment, and reduced incidence of aortic dissections, suggesting the importance of IL-6 signaling in inducing Th17-mediated aneurysmal progression. We further showed the pathological roles of Th17 lymphocytes by depleting Th17 by IL-17A neutralization or genetic mutation and showed decreased aortic chemokine MCP-1 production and macrophage recruitment, leading to a reduction in aortic dissections. We also established clinical relevance by showing increased Th17 infiltration into the aortic adventitial-medial border in patients with ascending aortic dissections. These findings indicate that IL-6 signaling converges on Th17 recruitment and IL-17A signaling upstream of macrophage recruitment, mediating vascular inflammation and aortic dissections. In another mouse model with spontaneous aortic aneurysms due to Marfan Syndrome (MFS) caused by Fbn-1 gene mutation (mgR homozygotes), we also reported elevated IL-6 signaling and increased macrophage recruitment in ascending aneurysmal tissues. To study the role of IL-6 signaling, we generated mgR homozygotes with IL-6 deficiency (DKOs), which showed reduction in aneurysmal dilation at late stage of disease with unaffected survival rate. Moreover, we reported that IL-6 deficiency led to decreased ECM degradation that is associated with reduced levels of local MMPs. These findings suggests the activation of IL-6-mediated inflammatory signaling contributed to aneurysmal progression in MFS through recruitment of leukocytes and stimulation of MMP expression, thus aggravating ECM degradation and vascular remodeling."],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["http://hdl.handle.net/2152.3/828"],"dc:subject":["Interleukin-6","Aortic aneurysms","Aortic dissections","Angiotensin II","Th17","marfan syndrome"],"dc:title":["The Role of IL-6 in Inflammatory Aortic Aneurysmal Diseases"],"dc:type":["Thesis"],"thesis:degree_discipline":["Cell Biology and Molecular Biology"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Biochemistry and Molecular Biology (Doctoral)"],"thesis:institution_name":["The University of Texas Medical Branch at Galveston"]},"updated_at":"2026-07-24T05:50:51Z"}