Smooth muscle cells in atherosclerosis: clones but not carbon copies
Our knowledge of the contribution of vascular smooth muscle cells (SMCs) to atherosclerosis has greatly advanced in the previous decade with the development of techniques allowing for the unambiguous identification and phenotypic characterization of SMC populations within the diseased vascular wall....
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | JVS - Vascular Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666350321000067 |
| _version_ | 1798035914909286400 |
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| author | Cristina Espinosa-Diez, PhD Varun Mandi, BS Mingyuan Du Mingjun Liu, MS Delphine Gomez, PhD |
| author_facet | Cristina Espinosa-Diez, PhD Varun Mandi, BS Mingyuan Du Mingjun Liu, MS Delphine Gomez, PhD |
| author_sort | Cristina Espinosa-Diez, PhD |
| collection | DOAJ |
| description | Our knowledge of the contribution of vascular smooth muscle cells (SMCs) to atherosclerosis has greatly advanced in the previous decade with the development of techniques allowing for the unambiguous identification and phenotypic characterization of SMC populations within the diseased vascular wall. By performing fate mapping or single-cell transcriptomics studies, or a combination of both, the field has made key observations: SMCs populate atherosclerotic lesions by the selective expansion and investment of a limited number of medial SMCs, which undergo profound and diverse modifications of their original phenotype and function. Thus, if SMCs residing within atherosclerotic lesions and contributing to the disease are clones, they are not carbon copies and can play atheroprotective or atheropromoting roles, depending on the nature of their phenotypic transitions. Tremendous progress has been made in identifying the transcriptional mechanisms biasing SMC fate. In the present review, we have summarized the recent advances in characterizing SMC investment and phenotypic diversity and the molecular mechanisms controlling SMC fate in atherosclerotic lesions. We have also discussed some of the remaining questions associated with these breakthrough observations. These questions include the underlying mechanisms regulating the phenomenon of SMC oligoclonal expansion; whether single-cell transcriptomics is reliable and sufficient to ascertain SMC functions and contributions during atherosclerosis development and progression; and how SMC clonality and phenotypic plasticity affects translational research and the therapeutic approaches developed to prevent atherosclerosis complications. Finally, we have discussed the complementary approaches the field should lean toward by combining single-cell phenotypic categorization and functional studies to understand further the complex SMC behavior and contribution in atherosclerosis. |
| first_indexed | 2024-04-11T21:05:03Z |
| format | Article |
| id | doaj.art-7ccc0f6943244333a111a8b3780dfb6a |
| institution | Directory Open Access Journal |
| issn | 2666-3503 |
| language | English |
| last_indexed | 2024-04-11T21:05:03Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JVS - Vascular Science |
| spelling | doaj.art-7ccc0f6943244333a111a8b3780dfb6a2022-12-22T04:03:22ZengElsevierJVS - Vascular Science2666-35032021-01-012136148Smooth muscle cells in atherosclerosis: clones but not carbon copiesCristina Espinosa-Diez, PhD0Varun Mandi, BS1Mingyuan Du2Mingjun Liu, MS3Delphine Gomez, PhD4Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PaPittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PaPittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pa; Department of Vascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, ChinaPittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pa; Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PaPittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pa; Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pa; Correspondence: Delphine Gomez, PhD, Division of Cardiology, Department of Medicine, University of Pittsburgh, 200 Lothrop St, Biomedical Science Tower, Rm 1723, Pittsburgh, PA 15261Our knowledge of the contribution of vascular smooth muscle cells (SMCs) to atherosclerosis has greatly advanced in the previous decade with the development of techniques allowing for the unambiguous identification and phenotypic characterization of SMC populations within the diseased vascular wall. By performing fate mapping or single-cell transcriptomics studies, or a combination of both, the field has made key observations: SMCs populate atherosclerotic lesions by the selective expansion and investment of a limited number of medial SMCs, which undergo profound and diverse modifications of their original phenotype and function. Thus, if SMCs residing within atherosclerotic lesions and contributing to the disease are clones, they are not carbon copies and can play atheroprotective or atheropromoting roles, depending on the nature of their phenotypic transitions. Tremendous progress has been made in identifying the transcriptional mechanisms biasing SMC fate. In the present review, we have summarized the recent advances in characterizing SMC investment and phenotypic diversity and the molecular mechanisms controlling SMC fate in atherosclerotic lesions. We have also discussed some of the remaining questions associated with these breakthrough observations. These questions include the underlying mechanisms regulating the phenomenon of SMC oligoclonal expansion; whether single-cell transcriptomics is reliable and sufficient to ascertain SMC functions and contributions during atherosclerosis development and progression; and how SMC clonality and phenotypic plasticity affects translational research and the therapeutic approaches developed to prevent atherosclerosis complications. Finally, we have discussed the complementary approaches the field should lean toward by combining single-cell phenotypic categorization and functional studies to understand further the complex SMC behavior and contribution in atherosclerosis.http://www.sciencedirect.com/science/article/pii/S2666350321000067Cell differentiationCell plasticityCoronary artery diseaseTranscriptomicsVascular cellVascular disease |
| spellingShingle | Cristina Espinosa-Diez, PhD Varun Mandi, BS Mingyuan Du Mingjun Liu, MS Delphine Gomez, PhD Smooth muscle cells in atherosclerosis: clones but not carbon copies JVS - Vascular Science Cell differentiation Cell plasticity Coronary artery disease Transcriptomics Vascular cell Vascular disease |
| title | Smooth muscle cells in atherosclerosis: clones but not carbon copies |
| title_full | Smooth muscle cells in atherosclerosis: clones but not carbon copies |
| title_fullStr | Smooth muscle cells in atherosclerosis: clones but not carbon copies |
| title_full_unstemmed | Smooth muscle cells in atherosclerosis: clones but not carbon copies |
| title_short | Smooth muscle cells in atherosclerosis: clones but not carbon copies |
| title_sort | smooth muscle cells in atherosclerosis clones but not carbon copies |
| topic | Cell differentiation Cell plasticity Coronary artery disease Transcriptomics Vascular cell Vascular disease |
| url | http://www.sciencedirect.com/science/article/pii/S2666350321000067 |
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