{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/113308"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/113308","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Β-carotene promotes atherosclerosis resolution and alleviates liver inflammation in a reversible murine model of atherosclerosis: A potential role of regulatory T cells","abstract":"Background: β-carotene has several health benefits on lipid metabolism, most of which are mediated through its provitamin A activity. Our laboratory has recently shown that β-carotene conversion to vitamin A is associated with reduced circulating cholesterol levels in mice and humans. Objective: To study the effect of β-carotene on atherosclerosis regression and hepatic inflammation. Methods: We utilized various animal models to study atherosclerosis regression: In our first model, we used weekly injections of an antisense oligonucleotide targeting the expression of the low-density lipoprotein receptor (LDLR ASO). To facilitate the development of atherosclerotic lesions, we fed these mice a Western diet (0.3% cholesterol, 41% of calories from fat) deficient in vitamin A (WD-VAD) for 16 weeks, after which we harvested the baseline group. The remaining mice underwent regression by stopping the LDLR ASO injections and injecting them once with LDLR SO, which binds and deactivates LDLR ASO. To study the role of β-carotene on atherosclerosis regression, we maintained a subset of mice on the same diet (WD-VAD), and another subset fed with a WD-VAD supplemented with 50 mg/kg of β-carotene (WD-β-carotene) for three weeks. To test the implication of regulatory T cells (Tregs) in β-carotene-induced atherosclerosis regression, we treated a group of mice with an anti-CD25 monoclonal antibody to deplete Tregs during regression. For all experiments, aortic roots, plasma, and tissues were collected and analyzed using morphometric and biochemical methods. Liver samples were harvested for RNA sequencing and histological analyses. Results: Baseline mice showed an increase in cholesterol levels in comparison to all regression groups, independently of the presence of β-carotene in the diet. These changes occurred independently of alterations in body weight. For the LDLR ASO model, histological analyses of aortic roots failed to show differences in atherosclerotic lesion area between groups, although we observed a reduction in the macrophage content in both regression groups that was more pronounced in WD-β-carotene-fed mice; baseline vs regression-VAD (~30%, P=0.053), and baseline vs regression-β-carotene (~42%, P<0.005). Collagen content in plaques, an indicator of plaque stability in humans, showed an increase in both regression groups; baseline vs regression-VAD (~217%, P <0.005), and baseline vs regression-β-carotene (~308%, P<0.0001). Lastly, anti-CD25 infusions decreased Tregs content in plasma and spleen. We also analyzed the liver using RNA sequencing and immunostaining. We found that the baseline mice showed a significant increase in hepatic macrophage accumulation in comparison to both regression groups. However, β-carotene showed a more pronounced effect on reducing hepatic inflammation compared to VAD. Conclusion: β-carotene enhances atherosclerosis resolution, as observed by a reduction in plaque macrophage content accompanied with an increase in collagen content. Atherosclerosis resolution is associated with a reduction in hepatic macrophage content and β-carotene enhances these positive effects.","abstract_html":"Background: β-carotene has several health benefits on lipid metabolism, most of which are mediated through its provitamin A activity. Our laboratory has recently shown that β-carotene conversion to vitamin A is associated with reduced circulating cholesterol levels in mice and humans. Objective: To study the effect of β-carotene on atherosclerosis regression and hepatic inflammation. Methods: We utilized various animal models to study atherosclerosis regression: In our first model, we used weekly injections of an antisense oligonucleotide targeting the expression of the low-density lipoprotein receptor (LDLR ASO). To facilitate the development of atherosclerotic lesions, we fed these mice a Western diet (0.3% cholesterol, 41% of calories from fat) deficient in vitamin A (WD-VAD) for 16 weeks, after which we harvested the baseline group. The remaining mice underwent regression by stopping the LDLR ASO injections and injecting them once with LDLR SO, which binds and deactivates LDLR ASO. To study the role of β-carotene on atherosclerosis regression, we maintained a subset of mice on the same diet (WD-VAD), and another subset fed with a WD-VAD supplemented with 50 mg/kg of β-carotene (WD-β-carotene) for three weeks. To test the implication of regulatory T cells (Tregs) in β-carotene-induced atherosclerosis regression, we treated a group of mice with an anti-CD25 monoclonal antibody to deplete Tregs during regression. For all experiments, aortic roots, plasma, and tissues were collected and analyzed using morphometric and biochemical methods. Liver samples were harvested for RNA sequencing and histological analyses. Results: Baseline mice showed an increase in cholesterol levels in comparison to all regression groups, independently of the presence of β-carotene in the diet. These changes occurred independently of alterations in body weight. For the LDLR ASO model, histological analyses of aortic roots failed to show differences in atherosclerotic lesion area between groups, although we observed a reduction in the macrophage content in both regression groups that was more pronounced in WD-β-carotene-fed mice; baseline vs regression-VAD (~30%, P=0.053), and baseline vs regression-β-carotene (~42%, P&lt;0.005). Collagen content in plaques, an indicator of plaque stability in humans, showed an increase in both regression groups; baseline vs regression-VAD (~217%, P &lt;0.005), and baseline vs regression-β-carotene (~308%, P&lt;0.0001). Lastly, anti-CD25 infusions decreased Tregs content in plasma and spleen. We also analyzed the liver using RNA sequencing and immunostaining. We found that the baseline mice showed a significant increase in hepatic macrophage accumulation in comparison to both regression groups. However, β-carotene showed a more pronounced effect on reducing hepatic inflammation compared to VAD. Conclusion: β-carotene enhances atherosclerosis resolution, as observed by a reduction in plaque macrophage content accompanied with an increase in collagen content. Atherosclerosis resolution is associated with a reduction in hepatic macrophage content and β-carotene enhances these positive effects.","abstract_has_math":false,"creators":["Albakri, Asma'a Ghaleb Ali"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Nutritional Sciences","degree_department":null,"school":null,"contributors":["Amengual, Jaume","Swanson, Kelly","Nakamura, Manabu","Erdman, John"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-01-12T22:56:05Z","date_published":"2022-01-12T22:56:05Z","updated_at":"2026-07-22T22:24:53Z","subjects":["β-carotene","atherosclerosis regression","low density lipoprotein","regulatory T cells","Hepatic inflammation"],"languages":["en"],"rights":["Copyright 2021 Asma’a Ghaleb Ali Albakri"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/113308","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Amengual, Jaume","Swanson, Kelly","Nakamura, Manabu","Erdman, John"]},{"key":"dc:creator","label":"Author","values":["Albakri, Asma'a Ghaleb Ali"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2022-01-12T22:56:05Z","2024-01-12T22:56:20Z","2021-07-15","2021-08"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Nutritional Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["β-carotene","atherosclerosis regression","low density lipoprotein","regulatory T cells","Hepatic inflammation"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2021 Asma’a Ghaleb Ali Albakri"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/113308"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Background: β-carotene has several health benefits on lipid metabolism, most of which are mediated through its provitamin A activity. Our laboratory has recently shown that β-carotene conversion to vitamin A is associated with reduced circulating cholesterol levels in mice and humans. Objective: To study the effect of β-carotene on atherosclerosis regression and hepatic inflammation. Methods: We utilized various animal models to study atherosclerosis regression: In our first model, we used weekly injections of an antisense oligonucleotide targeting the expression of the low-density lipoprotein receptor (LDLR ASO). To facilitate the development of atherosclerotic lesions, we fed these mice a Western diet (0.3% cholesterol, 41% of calories from fat) deficient in vitamin A (WD-VAD) for 16 weeks, after which we harvested the baseline group. The remaining mice underwent regression by stopping the LDLR ASO injections and injecting them once with LDLR SO, which binds and deactivates LDLR ASO. To study the role of β-carotene on atherosclerosis regression, we maintained a subset of mice on the same diet (WD-VAD), and another subset fed with a WD-VAD supplemented with 50 mg/kg of β-carotene (WD-β-carotene) for three weeks. To test the implication of regulatory T cells (Tregs) in β-carotene-induced atherosclerosis regression, we treated a group of mice with an anti-CD25 monoclonal antibody to deplete Tregs during regression. For all experiments, aortic roots, plasma, and tissues were collected and analyzed using morphometric and biochemical methods. Liver samples were harvested for RNA sequencing and histological analyses. Results: Baseline mice showed an increase in cholesterol levels in comparison to all regression groups, independently of the presence of β-carotene in the diet. These changes occurred independently of alterations in body weight. For the LDLR ASO model, histological analyses of aortic roots failed to show differences in atherosclerotic lesion area between groups, although we observed a reduction in the macrophage content in both regression groups that was more pronounced in WD-β-carotene-fed mice; baseline vs regression-VAD (~30%, P=0.053), and baseline vs regression-β-carotene (~42%, P<0.005). Collagen content in plaques, an indicator of plaque stability in humans, showed an increase in both regression groups; baseline vs regression-VAD (~217%, P <0.005), and baseline vs regression-β-carotene (~308%, P<0.0001). Lastly, anti-CD25 infusions decreased Tregs content in plasma and spleen. We also analyzed the liver using RNA sequencing and immunostaining. We found that the baseline mice showed a significant increase in hepatic macrophage accumulation in comparison to both regression groups. However, β-carotene showed a more pronounced effect on reducing hepatic inflammation compared to VAD. Conclusion: β-carotene enhances atherosclerosis resolution, as observed by a reduction in plaque macrophage content accompanied with an increase in collagen content. Atherosclerosis resolution is associated with a reduction in hepatic macrophage content and β-carotene enhances these positive effects.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2023-08-01","The student, Asma'a Albakri, accepted the attached license on 2021-07-12 at 15:12.","The student, Asma'a Albakri, submitted this Dissertation for approval on 2021-07-12 at 15:32.","This Dissertation was approved for publication on 2021-07-15 at 07:57.","DSpace SAF Submission Ingestion Package generated from Vireo submission #16879 on 2022-01-12 at 13:04:40","Made available in DSpace on 2022-01-12T22:56:05Z (GMT). No. of bitstreams: 4 ALBAKRI-DISSERTATION-2021.pdf: 4411184 bytes, checksum: 821fde9dbcc81b732827014d770b14a8 (MD5) Albakri Asma'a_PhD Dissertation_210712.docx: 17801699 bytes, checksum: 20d78a2733a86fc9c1c5468f374c3b21 (MD5) LICENSE.txt: 4211 bytes, checksum: 5dbe1c46b841b830246abcf08d67e973 (MD5) PROQUEST_LICENSE.txt: 4557 bytes, checksum: bf568356c42b6712927195cf3adc9e30 (MD5) Previous issue date: 2021-07-15","Embargo set by: Seth Robbins for item 121237 Lift date: 2024-01-12T22:56:20Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Author requested closed access (OA after 2yrs) in Vireo ETD system","Limited"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Β-carotene promotes atherosclerosis resolution and alleviates liver inflammation in a reversible murine model of atherosclerosis: A potential role of regulatory T cells"]}]}],"canonical_facts":{"dc:contributor":["Amengual, Jaume","Swanson, Kelly","Nakamura, Manabu","Erdman, John"],"dc:creator":["Albakri, Asma'a Ghaleb Ali"],"dc:date":["2022-01-12T22:56:05Z","2024-01-12T22:56:20Z","2021-07-15","2021-08"],"dc:description":["Background: β-carotene has several health benefits on lipid metabolism, most of which are mediated through its provitamin A activity. Our laboratory has recently shown that β-carotene conversion to vitamin A is associated with reduced circulating cholesterol levels in mice and humans. Objective: To study the effect of β-carotene on atherosclerosis regression and hepatic inflammation. Methods: We utilized various animal models to study atherosclerosis regression: In our first model, we used weekly injections of an antisense oligonucleotide targeting the expression of the low-density lipoprotein receptor (LDLR ASO). To facilitate the development of atherosclerotic lesions, we fed these mice a Western diet (0.3% cholesterol, 41% of calories from fat) deficient in vitamin A (WD-VAD) for 16 weeks, after which we harvested the baseline group. The remaining mice underwent regression by stopping the LDLR ASO injections and injecting them once with LDLR SO, which binds and deactivates LDLR ASO. To study the role of β-carotene on atherosclerosis regression, we maintained a subset of mice on the same diet (WD-VAD), and another subset fed with a WD-VAD supplemented with 50 mg/kg of β-carotene (WD-β-carotene) for three weeks. To test the implication of regulatory T cells (Tregs) in β-carotene-induced atherosclerosis regression, we treated a group of mice with an anti-CD25 monoclonal antibody to deplete Tregs during regression. For all experiments, aortic roots, plasma, and tissues were collected and analyzed using morphometric and biochemical methods. Liver samples were harvested for RNA sequencing and histological analyses. Results: Baseline mice showed an increase in cholesterol levels in comparison to all regression groups, independently of the presence of β-carotene in the diet. These changes occurred independently of alterations in body weight. For the LDLR ASO model, histological analyses of aortic roots failed to show differences in atherosclerotic lesion area between groups, although we observed a reduction in the macrophage content in both regression groups that was more pronounced in WD-β-carotene-fed mice; baseline vs regression-VAD (~30%, P=0.053), and baseline vs regression-β-carotene (~42%, P<0.005). Collagen content in plaques, an indicator of plaque stability in humans, showed an increase in both regression groups; baseline vs regression-VAD (~217%, P <0.005), and baseline vs regression-β-carotene (~308%, P<0.0001). Lastly, anti-CD25 infusions decreased Tregs content in plasma and spleen. We also analyzed the liver using RNA sequencing and immunostaining. We found that the baseline mice showed a significant increase in hepatic macrophage accumulation in comparison to both regression groups. However, β-carotene showed a more pronounced effect on reducing hepatic inflammation compared to VAD. Conclusion: β-carotene enhances atherosclerosis resolution, as observed by a reduction in plaque macrophage content accompanied with an increase in collagen content. Atherosclerosis resolution is associated with a reduction in hepatic macrophage content and β-carotene enhances these positive effects.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2023-08-01","The student, Asma'a Albakri, accepted the attached license on 2021-07-12 at 15:12.","The student, Asma'a Albakri, submitted this Dissertation for approval on 2021-07-12 at 15:32.","This Dissertation was approved for publication on 2021-07-15 at 07:57.","DSpace SAF Submission Ingestion Package generated from Vireo submission #16879 on 2022-01-12 at 13:04:40","Made available in DSpace on 2022-01-12T22:56:05Z (GMT). No. of bitstreams: 4 ALBAKRI-DISSERTATION-2021.pdf: 4411184 bytes, checksum: 821fde9dbcc81b732827014d770b14a8 (MD5) Albakri Asma'a_PhD Dissertation_210712.docx: 17801699 bytes, checksum: 20d78a2733a86fc9c1c5468f374c3b21 (MD5) LICENSE.txt: 4211 bytes, checksum: 5dbe1c46b841b830246abcf08d67e973 (MD5) PROQUEST_LICENSE.txt: 4557 bytes, checksum: bf568356c42b6712927195cf3adc9e30 (MD5) Previous issue date: 2021-07-15","Embargo set by: Seth Robbins for item 121237 Lift date: 2024-01-12T22:56:20Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Author requested closed access (OA after 2yrs) in Vireo ETD system","Limited"],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/2142/113308"],"dc:language":["en"],"dc:rights":["Copyright 2021 Asma’a Ghaleb Ali Albakri"],"dc:subject":["β-carotene","atherosclerosis regression","low density lipoprotein","regulatory T cells","Hepatic inflammation"],"dc:title":["Β-carotene promotes atherosclerosis resolution and alleviates liver inflammation in a reversible murine model of atherosclerosis: A potential role of regulatory T cells"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Nutritional Sciences"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:24:53Z"}