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4369 Reprogramming of vascular smooth muscle cells to multipotent progenitor cells contributes to progression of atherosclerosis
OBJECTIVES/GOALS: Our lab previously identified a population of vascular smooth muscle (SMC)-derived progenitor cells (AdvSca1-SM) which expand robustly in response to disease and can differentiate into multiple cell types. We now aim to define the role of these AdvSca1-SM cells in atherosclerotic p...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cambridge University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8822919/ http://dx.doi.org/10.1017/cts.2020.315 |
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author | Dubner, Allison Milfred Lu, Sizhao Jolly, Austin Strand, Keith Mutryn, Marie Tucker, Rebecca Moulton, Karen Nemenoff, Raphael A. Weiser-Evans, Mary C.M. |
author_facet | Dubner, Allison Milfred Lu, Sizhao Jolly, Austin Strand, Keith Mutryn, Marie Tucker, Rebecca Moulton, Karen Nemenoff, Raphael A. Weiser-Evans, Mary C.M. |
author_sort | Dubner, Allison Milfred |
collection | PubMed |
description | OBJECTIVES/GOALS: Our lab previously identified a population of vascular smooth muscle (SMC)-derived progenitor cells (AdvSca1-SM) which expand robustly in response to disease and can differentiate into multiple cell types. We now aim to define the role of these AdvSca1-SM cells in atherosclerotic plaque progression. METHODS/STUDY POPULATION: Goal one uses SMC lineage tracing mice and a model of atherosclerosis to track reprogramming of SMCs to AdvSca1-SM cells in the setting of disease. Arteries are analyzed using flow cytometry and immunofluorescence to quantify changes in number of mature SMCs and AdvSca1-SM cells. Goal two uses AdvSca1-SM lineage tracing mice with high cholesterol-induced atherosclerosis and plaque neovascularization. Arteries are analyzed to quantify expansion of AdvSca1-SM cells, subsequent re-differentiation into mature SMC, endothelial cells, or macrophages, and contribution to plaque neovascularization. Mechanistic findings from both goals are being investigated in diseased human coronary arteries. RESULTS/ANTICIPATED RESULTS: Flow cytometry from SMC lineage tracing mice revealed a 7- to 13-fold expansion of AdvSca1-SM cells in carotid arteries (p<0.001) and aortas (p = 0.03) after 6 weeks of western diet; no differences in macrophage numbers were observed. Additional SMC and AdvSca1-SM cell lineage tracing mice are on atherogenic diets to assess early and advanced atherosclerosis. We predict that AdvSca1-SM cells will contribute to macrophage accumulation as well as plaque neovascularization in the setting of severe atherosclerosis. Translational relevance of mechanisms driving SMC reprogramming and AdvSca1-SM cell contribution to plaque progression are being applied to studies of diseased human coronary arteries. DISCUSSION/SIGNIFICANCE OF IMPACT: Our data suggest a role for AdvSca1-SM cells in atherosclerosis. Ongoing work will clarify the mechanisms driving plaque-associated AdvSca1-SM expansion and define the ultimate fates of these cells. In vivo modulation of this process could provide the basis for future anti-atherosclerotic therapies. CONFLICT OF INTEREST DESCRIPTION: AD - CCTSI TOTTS TL1TR002533; SL - 18POST34030397 from the American Heart Association; AJ – no conflicts; KS - 1F31HL147393 from the National Heart, Lung, and Blood Institute, NIH; MM – no conflicts; RT – no conflicts; KSM – no conflicts; RAN - R01CA236222 from the National Cancer Institute, NIH, and 2018-03 from the Lungevity Foundation; and MCMW-E - R01 HL121877 from the National Heart, Lung, and Blood Institute, NIH, and 25A8679 from the Chernowitz Foundation. |
format | Online Article Text |
id | pubmed-8822919 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cambridge University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-88229192022-02-18 4369 Reprogramming of vascular smooth muscle cells to multipotent progenitor cells contributes to progression of atherosclerosis Dubner, Allison Milfred Lu, Sizhao Jolly, Austin Strand, Keith Mutryn, Marie Tucker, Rebecca Moulton, Karen Nemenoff, Raphael A. Weiser-Evans, Mary C.M. J Clin Transl Sci Mechanistic Basic to Clinical OBJECTIVES/GOALS: Our lab previously identified a population of vascular smooth muscle (SMC)-derived progenitor cells (AdvSca1-SM) which expand robustly in response to disease and can differentiate into multiple cell types. We now aim to define the role of these AdvSca1-SM cells in atherosclerotic plaque progression. METHODS/STUDY POPULATION: Goal one uses SMC lineage tracing mice and a model of atherosclerosis to track reprogramming of SMCs to AdvSca1-SM cells in the setting of disease. Arteries are analyzed using flow cytometry and immunofluorescence to quantify changes in number of mature SMCs and AdvSca1-SM cells. Goal two uses AdvSca1-SM lineage tracing mice with high cholesterol-induced atherosclerosis and plaque neovascularization. Arteries are analyzed to quantify expansion of AdvSca1-SM cells, subsequent re-differentiation into mature SMC, endothelial cells, or macrophages, and contribution to plaque neovascularization. Mechanistic findings from both goals are being investigated in diseased human coronary arteries. RESULTS/ANTICIPATED RESULTS: Flow cytometry from SMC lineage tracing mice revealed a 7- to 13-fold expansion of AdvSca1-SM cells in carotid arteries (p<0.001) and aortas (p = 0.03) after 6 weeks of western diet; no differences in macrophage numbers were observed. Additional SMC and AdvSca1-SM cell lineage tracing mice are on atherogenic diets to assess early and advanced atherosclerosis. We predict that AdvSca1-SM cells will contribute to macrophage accumulation as well as plaque neovascularization in the setting of severe atherosclerosis. Translational relevance of mechanisms driving SMC reprogramming and AdvSca1-SM cell contribution to plaque progression are being applied to studies of diseased human coronary arteries. DISCUSSION/SIGNIFICANCE OF IMPACT: Our data suggest a role for AdvSca1-SM cells in atherosclerosis. Ongoing work will clarify the mechanisms driving plaque-associated AdvSca1-SM expansion and define the ultimate fates of these cells. In vivo modulation of this process could provide the basis for future anti-atherosclerotic therapies. CONFLICT OF INTEREST DESCRIPTION: AD - CCTSI TOTTS TL1TR002533; SL - 18POST34030397 from the American Heart Association; AJ – no conflicts; KS - 1F31HL147393 from the National Heart, Lung, and Blood Institute, NIH; MM – no conflicts; RT – no conflicts; KSM – no conflicts; RAN - R01CA236222 from the National Cancer Institute, NIH, and 2018-03 from the Lungevity Foundation; and MCMW-E - R01 HL121877 from the National Heart, Lung, and Blood Institute, NIH, and 25A8679 from the Chernowitz Foundation. Cambridge University Press 2020-07-29 /pmc/articles/PMC8822919/ http://dx.doi.org/10.1017/cts.2020.315 Text en © The Association for Clinical and Translational Science 2020 https://creativecommons.org/licenses/by/4.0/This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Mechanistic Basic to Clinical Dubner, Allison Milfred Lu, Sizhao Jolly, Austin Strand, Keith Mutryn, Marie Tucker, Rebecca Moulton, Karen Nemenoff, Raphael A. Weiser-Evans, Mary C.M. 4369 Reprogramming of vascular smooth muscle cells to multipotent progenitor cells contributes to progression of atherosclerosis |
title | 4369 Reprogramming of vascular smooth muscle cells to multipotent progenitor cells contributes to progression of atherosclerosis |
title_full | 4369 Reprogramming of vascular smooth muscle cells to multipotent progenitor cells contributes to progression of atherosclerosis |
title_fullStr | 4369 Reprogramming of vascular smooth muscle cells to multipotent progenitor cells contributes to progression of atherosclerosis |
title_full_unstemmed | 4369 Reprogramming of vascular smooth muscle cells to multipotent progenitor cells contributes to progression of atherosclerosis |
title_short | 4369 Reprogramming of vascular smooth muscle cells to multipotent progenitor cells contributes to progression of atherosclerosis |
title_sort | 4369 reprogramming of vascular smooth muscle cells to multipotent progenitor cells contributes to progression of atherosclerosis |
topic | Mechanistic Basic to Clinical |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8822919/ http://dx.doi.org/10.1017/cts.2020.315 |
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