Extensive Proliferation of a Subset of Differentiated, yet Plastic, Medial Vascular Smooth Muscle Cells Contributes to Neointimal Formation in Mouse Injury and Atherosclerosis Models
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Rationale: Vascular smooth muscle cell (VSMC) accumulation is a hallmark of atherosclerosis and vascular injury. However, fundamental aspects of proliferation and the phenotypic changes within individual VSMCs, which underlie vascular disease, remain unresolved. In particular, it is not known whether all VSMCs proliferate and display plasticity or whether individual cells can switch to multiple phenotypes. Objective: To assess whether proliferation and plasticity in disease is a general characteristic of VSMCs or a feature of a subset of cells. Methods and Results: Using multicolor lineage labeling, we demonstrate that VSMCs in injury-induced neointimal lesions and in atherosclerotic plaques are oligoclonal, derived from few expanding cells. Lineage tracing also revealed that the progeny of individual VSMCs contributes to both alpha smooth muscle actin (aSma)–positive fibrous cap and Mac3-expressing macrophage-like plaque core cells. Costaining for phenotypic markers further identified a double-positive aSma+ Mac3+ cell population, which is specific to VSMC-derived plaque cells. In contrast, VSMC-derived cells generating the neointima after vascular injury generally retained the expression of VSMC markers and the upregulation of Mac3 was less pronounced. Monochromatic regions in atherosclerotic plaques and injury-induced neointima did not contain VSMC-derived cells expressing a different fluorescent reporter protein, suggesting that proliferation-independent VSMC migration does not make a major contribution to VSMC accumulation in vascular disease. Conclusions: We demonstrate that extensive proliferation of a low proportion of highly plastic VSMCs results in the observed VSMC accumulation after injury and in atherosclerotic plaques. Therapeutic targeting of these hyperproliferating VSMCs might effectively reduce vascular disease without affecting vascular integrity.
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Lineage tracing studies have unambiguously demonstrated that VSMCs contribute substantially to plaque formation in murine models of atherosclerosis, generating 30-70% of all plaque cells.
“Lineage tracing studies have unambiguously demonstrated that VSMCs contribute substantially to plaque formation in murine models of atherosclerosis, generating 30-70% of all plaque cells 11,18-20,22,23 .”
From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [20]
Within plaques a large proportion of reporter-expressing VSMC-derived cells do not have detectable levels of the contractile smooth muscle cell marker αSMA.
“Within plaques a large proportion of reporter-expressing VSMC-derived cells do not have detectable levels of the contractile smooth muscle cell marker α SMA 11,20 .”
From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [20]
Some plaque reporter-expressing cells were positive for Mac-3, Lgals3 and CD68, markers previously used to study macrophages in atherosclerosis.
“Instead, some plaque reporter-expressing cells were positive for Mac-3 20 , Lgals3 11 and CD68 17 - markers that have been previously used to study macrophages in atherosclerosis.”
From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [20]
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Vascular smooth muscle cells in atherosclerosis
Bennett, M. R., Sinha, S., & Owens, G. K. (2016) · Circulation Research · doi:10.1161/circresaha.115.306361 · Cited by 2,179 · see citing works
Self-citationSnippert, H. J., van der Flier, L. G., Sato, T., van Es, J. H., van den Born, M., Kroon-Veenboer, C., Barker, N., Klein, A. M., van Rheenen, J., Simons, B. D., et al. (2010) · Cell · doi:10.1016/j.cell.2010.09.016 · Cited by 1,951 · see citing works
Self-citationClowes, A. W., Reidy, M. A., & Mm, C. (1983) · PubMed · Cited by 1,439 · see citing works
Shankman, L. S., Gomez, D., Cherepanova, O. A., Salmon, M., Alencar, G. F., Haskins, R. M., Swiatlowska, P., Newman, A. A. C., Greene, E. S., Straub, A. C., et al. (2015) · Nature Medicine · doi:10.1038/nm.3866 · Cited by 1,218 · see citing works
Piedrahita, J. A., Zhang, S. H., Hagaman, J. R., Oliver, P. M., & Maeda, N. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.10.4471 · Cited by 944 · see citing works
Regulation and characteristics of vascular smooth muscle cell phenotypic diversity
Rensen, S. S., Doevendans, P. A., & van Eys, G. J. J. M. (2007) · Netherlands Heart Journal · doi:10.1007/bf03085963 · Cited by 917 · see citing works
Evidence for a Monoclonal Origin of Human Atherosclerotic Plaques
Benditt, E. P., & Benditt, J. M. (1973) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.70.6.1753 · Cited by 913 · see citing works
Shankman, L. S., Gomez, D. A., Cherepanova, O. A., Salmon, M., Alencar, G. F., Haskins, R. M., Swiatlowska, P., Newman, A. A. C., Greene, E. S., Straub, A. C., et al. (2016) · Nature Medicine · doi:10.1038/nm0216-217a · Cited by 775 · see citing works
Alexander, M. R., & Owens, G. K. (2011) · Annual Review of Physiology · doi:10.1146/annurev-physiol-012110-142315 · Cited by 771 · see citing works
G12-G13–LARG–mediated signaling in vascular smooth muscle is required for salt-induced hypertension
Wirth, A., Benyó, Z., Lukasova, M., Leutgeb, B., Wettschureck, N., Gorbey, S., Örsy, P., Horváth, B., Maser‐Gluth, C., Greiner, E. F., et al. (2007) · Nature Medicine · doi:10.1038/nm1666 · Cited by 671 · see citing works
Clarke, M. C. H., Figg, N. L., Maguire, J. J., Davenport, A. P., Goddard, M. J., Littlewood, T. D., & Bennett, M. R. (2006) · Nature Medicine · doi:10.1038/nm1459 · Cited by 645 · see citing works
Self-citationMatthews, C., Gorenne, I., Scott, S., Figg, N., Kirkpatrick, P., Ritchie, A., Goddard, M., & Bennett, M. (2006) · Circulation Research · doi:10.1161/01.res.0000233315.38086.bc · Cited by 615 · cited 1× · see citing works
“replicative exhaustion, telomere shortening, and increased senescence observed in human plaques.(22,23) Consistent with”
Self-citationTransdifferentiation of Vascular Smooth Muscle Cells to Macrophage-Like Cells During Atherogenesis
Feil, S., Fehrenbacher, B., Lukowski, R., Essmann, F., Schulze-Osthoff, K., Schaller, M., & Feil, R. (2014) · Circulation Research · doi:10.1161/circresaha.115.304634 · Cited by 578 · see citing works
Significance of quiescent smooth muscle migration in the injured rat carotid artery.
CLOWES, A. W., & Schwartz, S. M. (1985) · Circulation Research · doi:10.1161/01.res.56.1.139 · Cited by 575 · see citing works
Remodeling With Neointima Formation in the Mouse Carotid Artery After Cessation of Blood Flow
Kumar, A. F., & Lindner, V. (1997) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.17.10.2238 · Cited by 532 · see citing works
Significance of quiescent smooth muscle migration in the injured rat carotid artery.
WClowes, A., & MSchwartz, S. (1985) · Circulation Research · Cited by 337 · see citing works
Gardner, S. E., Humphry, M., Bennett, M. R., & Clarke, M. C. H. (2015) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.115.305896 · Cited by 285 · see citing works
Self-citationDetection of histone modifications at specific gene loci in single cells in histological sections
Gomez, D., Shankman, L. S., Nguyen, A. T., & Owens, G. K. (2013) · Nature Methods · doi:10.1038/nmeth.2332 · Cited by 253 · see citing works
Multiple repressor pathways contribute to phenotypic switching of vascular smooth muscle cells
Kawai‐Kowase, K., & Owens, G. K. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00394.2006 · Cited by 245 · see citing works
Smooth muscle cell progenitors are primed to muscularize in pulmonary hypertension
Sheikh, A. Q., Misra, A., Rosas, I. O., Adams, R. H., & Greif, D. M. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aaa9712 · Cited by 174 · see citing works
Herring, B. P., Hoggatt, A. M., Burlak, C., & Offermanns, S. (2014) · Vascular Cell · doi:10.1186/2045-824x-6-21 · Cited by 140 · see citing works
Nemenoff, R. A., Horita, H. N., Ostriker, A. C., Furgeson, S. B., Simpson, P. A., VanPutten, V., Crossno, J. T., Offermanns, S., & Weiser‐Evans, M. C. M. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.223701 · Cited by 133 · see citing works
Smooth Muscle Phenotypic Modulation—A Personal Experience
Campbell, J. H., & CAMPBELL, G. R. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.243212 · Cited by 126 · see citing works
Lineage tracing of cells involved in atherosclerosis
Albarrán-Juárez, J., Kaur, H., Grimm, M., Offermanns, S., & Wettschureck, N. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.06.012 · Cited by 90 · see citing works
Yu, H., Clarke, M. C. H., Figg, N. L., Littlewood, T. D., & Bennett, M. R. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.235622 · Cited by 76 · see citing works
Self-citationMechanical properties and structure of carotid arteries in mice lacking desmin
Lacolley, P. J., Challande, P., Boumaza, S., Cohuet, G., Laurent, S., Boutouyrie, P., Grimaud, J.-A., Paulin, D., Lamazière, J. D., & Li, Z. (2001) · Cardiovascular Research · doi:10.1016/s0008-6363(01)00278-4 · Cited by 73 · see citing works
Yu, H., Stoneman, V. E. A., Clarke, M. C. H., Figg, N. L., Xin, H., Kotlikoff, M. I., Littlewood, T. D., & Bennett, M. R. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.218578 · Cited by 69 · see citing works
Self-citationIntegrin β3 inhibition is a therapeutic strategy for supravalvular aortic stenosis
Misra, A., Sheikh, A. Q., Kumar, A., Luo, J., Zhang, J., Hinton, R. B., Smoot, L. B., Kaplan, P. B., Urbán, Z., Qyang, Y., et al. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20150688 · Cited by 53 · see citing works
Alterations in population dynamics of arterial smooth muscle cells during atherogenesis
Thomas, W. A., Florentin, R. A., Reiner, J. M., Lee, W. M., & Lee, K. T. (1976) · Experimental and Molecular Pathology · doi:10.1016/0014-4800(76)90009-5 · Cited by 52 · see citing works
Characterization of Proliferating Lesion‐Resident Cells During All Stages of Atherosclerotic Growth
Lhoták, Š., Gyulay, G., Cutz, J., Al‐Hashimi, A., Trigatti, B. L., Richards, C. D., Igdoura, S. A., Steinberg, G. R., Bramson, J. L., Ask, K., et al. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.116.003945 · Cited by 45 · see citing works
Yang, P., Hong, M. S., Fu, C., Schmit, B. M., Su, Y., Berceli, S. A., & Jiang, Z. (2015) · Surgery · doi:10.1016/j.surg.2015.08.015 · Cited by 20 · see citing works
Josephy, P. D., Bibeau, K. L., & Evans, D. H. (2000) · Environmental and Molecular Mutagenesis · doi:10.1002/1098-2280(2000)35:4 · Cited by 15 · see citing works
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- [29]Andreassi MG Botto N Colombo MG Biagini A Clerico A Genetic instability and atherosclerosis: can somatic mutations account for the development of cardiovascular diseases? Environ Mol Mutagen 2000 35 265 269 doi: 10.1002/1098-2280 10861945 · DOI
Cited by
Sorted by citations
Borén, J., Chapman, M. J., Krauss, R. M., Packard, C. J., Bentzon, J. F., Binder, C. J., Daemen, M. J., Demer, L. L., Hegele, R. A., Nicholls, S. J., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz962 · Cited by 1,601 · see citing works
Vascular smooth muscle cells in atherosclerosis
Basatemur, G. L., Jørgensen, H. F., Clarke, M. C. H., Bennett, M. R., & Mallat, Z. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-019-0227-9 · Cited by 1,099 · see citing works
Self-citationTargeting inflammation in atherosclerosis — from experimental insights to the clinic
Soehnlein, O., & Libby, P. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00198-1 · Cited by 1,042 · see citing works
Wirka, R. C., Wagh, D. A., Paik, D. T., Pjanic, M., Nguyen, T., Miller, C. L., Kundu, R., Nagao, M., Coller, J., Koyano, T. K., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0512-5 · Cited by 880 · see citing works
Ouimet, M., Barrett, T. J., & Fisher, E. (2019) · Circulation Research · doi:10.1161/circresaha.119.312617 · Cited by 416 · see citing works
Pan, H., Xue, C., Auerbach, B. J., Fan, J., Bashore, A. C., Cui, J. G., Yang, D. Y., Trignano, S. B., Liu, W., Shi, J., et al. (2020) · Circulation · doi:10.1161/circulationaha.120.048378 · Cited by 623 · see citing works
Vascular smooth muscle cells in atherosclerosis: time for a re-assessment
Grootaert, M. O. J., & Bennett, M. R. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab046 · Cited by 518 · see citing works
Self-citationSmooth muscle cell fate and plasticity in atherosclerosis
Allahverdian, S., Chaâbane, C., Boukais, K., Francis, G. A., & Bochaton‐Piallat, M. (2018) · Cardiovascular Research · doi:10.1093/cvr/cvy022 · Cited by 507 · see citing works
Kim, K., Shim, D., Lee, J. S., Zaitsev, K., Williams, J. W., Kim, K.-W., Jang, M.-Y., Seok Jang, H., Yun, T. J., Lee, S. H., et al. (2018) · Circulation Research · doi:10.1161/circresaha.118.312804 · Cited by 434 · see citing works
How vascular smooth muscle cell phenotype switching contributes to vascular disease
Cao, G., Xuan, X., Hu, J. H., Zhang, R., Jin, H., & Dong, H. (2022) · Cell Communication and Signaling · doi:10.1186/s12964-022-00993-2 · Cited by 440 · see citing works
Smooth muscle cell-driven vascular diseases and molecular mechanisms of VSMC plasticity
Frismantiene, A., Philippova, M., Erné, P., & Resink, T. J. (2018) · Cellular Signalling · doi:10.1016/j.cellsig.2018.08.019 · Cited by 408 · see citing works
DNA hypermethylation in disease: mechanisms and clinical relevance
Ehrlich, M. (2019) · Epigenetics · doi:10.1080/15592294.2019.1638701 · Cited by 375 · see citing works
Fate and state of vascular smooth muscle cells in atherosclerosis
Miano, J. M., Fisher, E. A., & Majesky, M. W. (2021) · Circulation · doi:10.1161/circulationaha.120.049922 · Cited by 318 · see citing works
Dobnikar, L., Taylor, A. L., Chappell, J., Oldach, P., Harman, J. J., Oerton, E., Dzierzak, E. A., Bennett, M. R., Spivakov, M., & Jørgensen, H. F. (2018) · Nature Communications · doi:10.1038/s41467-018-06891-x · Cited by 303 · see citing works
Self-citationRole of Vascular Smooth Muscle Cell Plasticity and Interactions in Vessel Wall Inflammation
Sorokin, V., Vickneson, K., Kofidis, T., Woo, C. C., Lin, X. Y., Foo, R., & Shanahan, C. M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.599415 · Cited by 292 · see citing works
Smooth Muscle Cell Phenotypic Diversity
Liu, M., & Gomez, D. A. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.312131 · Cited by 284 · see citing works
Six Shades of Vascular Smooth Muscle Cells Illuminated by KLF4 (Krüppel-Like Factor 4)
Yap, C., Mieremet, A., de Vries, C. J. M., Micha, D., & de Waard, V. (2021) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.121.316600 · Cited by 281 · see citing works
Resident and Monocyte-Derived Macrophages in Cardiovascular Disease
Honold, L., & Nahrendorf, M. (2018) · Circulation Research · doi:10.1161/circresaha.117.311071 · Cited by 272 · see citing works
Smooth muscle cell and arterial aging: basic and clinical aspects
Lacolley, P. J., Regnault, V., & Avolio, A. P. (2018) · Cardiovascular Research · doi:10.1093/cvr/cvy009 · Cited by 222 · see citing works
Integrin beta3 regulates clonality and fate of smooth muscle-derived atherosclerotic plaque cells
Misra, A., Feng, Z., Chandran, R. R., Kabir, I., Rotllan, N., Aryal, B., Sheikh, A. Q., Ding, L., Qin, L., Fernández-Hernando, C., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04447-7 · Cited by 207 · see citing works
Phenotypic Switching of Vascular Smooth Muscle Cells in Atherosclerosis
Chen, R., McVey, D. G., Shen, D., Huang, X., & Ye, S. (2023) · Journal of the American Heart Association · doi:10.1161/jaha.123.031121 · Cited by 210 · see citing works
Li, Z., Solomonidis, E. G., Meloni, M., Taylor, R. S., Duffin, R., Dobie, R., Pinto, M. M., Henderson, B. E. P., Louwe, P. A., D’Amico, G., et al. (2019) · European Heart Journal · doi:10.1093/eurheartj/ehz305 · Cited by 208 · see citing works
Self-citationTargeting smooth muscle cell phenotypic switching in vascular disease
Chakraborty, R., Chatterjee, P., Dave, J. M., Ostriker, A. C., Greif, D. M., Rzucidlo, E. M., & Martin, K. A. (2021) · JVS Vascular Science · doi:10.1016/j.jvssci.2021.04.001 · Cited by 185 · see citing works
Vascular Smooth Muscle Cell Plasticity and Autophagy in Dissecting Aortic Aneurysms
Clément, M., Chappell, J., Raffort, J., Lareyre, F., Vandestienne, M., Taylor, A. L., Finigan, A., Harrison, J., Bennett, M. R., Bruneval, P., et al. (2019) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.118.311727 · Cited by 184 · see citing works
Self-citationJacobsen, K., Lund, M. B., Shim, J., Gunnersen, S., Füchtbauer, E.-M., Kjolby, M., Carramolino, L., & Bentzon, J. F. (2017) · JCI Insight · doi:10.1172/jci.insight.95890 · Cited by 172 · see citing works
Promoters to Study Vascular Smooth Muscle
Chakraborty, R., Saddouk, F. Z., Carrao, A. C. R., Krause, D. S., Greif, D. M., & Martin, K. A. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.312449 · Cited by 171 · see citing works
Vascular Macrophages in Atherosclerosis
Xu, H., Jiang, J., Chen, W., Li, W., & Chen, Z. (2019) · Journal of Immunology Research · doi:10.1155/2019/4354786 · Cited by 173 · see citing works
Fasolo, F., Jin, H., Winski, G., Chernogubova, E., Pauli, J., Winter, H., Li, D. Y., Glukha, N., Bauer, S., Metschl, S., et al. (2021) · Circulation · doi:10.1161/circulationaha.120.052023 · Cited by 167 · see citing works
Zhang, F. S., Guo, X. Q., Xia, Y., & Mao, L. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-04079-z · Cited by 170 · see citing works
Macrophages in vascular inflammation and atherosclerosis
Cochain, C., & Zernecke, A. (2017) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-017-1941-y · Cited by 164 · see citing works
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Pan, H., Ho, S. E., Xue, C., Cui, J. G., Johanson, Q., Sachs, N., Ross, L. S., Li, F., Solomon, R. A., Connolly, E. S., et al. (2024) · Circulation · doi:10.1161/circulationaha.123.067587 · Cited by 153 · see citing works
Arterial Sca1+ Vascular Stem Cells Generate De Novo Smooth Muscle for Artery Repair and Regeneration
Tang, J., Wang, H., Huang, X., Li, F., Zhu, H., Li, Y., He, L., Zhang, H., Pu, W., Liu, K., et al. (2019) · Cell stem cell · doi:10.1016/j.stem.2019.11.010 · Cited by 151 · see citing works
Elmarasi, M., Elmakaty, I., Elsayed, B., Elsayed, A., Zein, J. A., Boudaka, A., & Eid, A. H. (2024) · Journal of Cellular Physiology · doi:10.1002/jcp.31200 · Cited by 154 · see citing works
The role of smooth muscle cells in plaque stability: Therapeutic targeting potential
Harman, J. J., & Jørgensen, H. F. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14779 · Cited by 147 · see citing works
Self-citationAhmed, A. S. I., Dong, K., Liu, J., Wen, T., Yu, L., Xu, F., Kang, X., Osman, I., Hu, G., Bunting, K. M., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1803725115 · Cited by 145 · see citing works
Nox, Reactive Oxygen Species and Regulation of Vascular Cell Fate
Burtenshaw, D., Hakimjavadi, R., Redmond, E. M., & Cahill, P. A. (2017) · Antioxidants · doi:10.3390/antiox6040090 · Cited by 136 · see citing works
Vascular smooth muscle cells in intimal hyperplasia, an update
Déglise, S., Bechelli, C., & Allagnat, F. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2022.1081881 · Cited by 135 · see citing works
Wang, Y., Nanda, V., DiRenzo, D. M., Ye, J., Xiao, S., Kojima, Y., Howe, K. L., Jarr, K.-U., Flores, A. M., Tsantilas, P., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2006348117 · Cited by 132 · see citing works
Role of Resident Stem Cells in Vessel Formation and Arteriosclerosis
Zhang, L., Bhaloo, S. I., Chen, T., Zhou, B., & Xu, Q. (2018) · Circulation Research · doi:10.1161/circresaha.118.313058 · Cited by 132 · see citing works
Aortic Aneurysms and Dissections Series
Shen, Y. H., LeMaire, S. A., Webb, N. R., Cassis, L. A., Daugherty, A., & Lu, H. S. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.313991 · Cited by 130 · see citing works
TGFβ, smooth muscle cells and coronary artery disease: a review
Low, E. L., Baker, A. H., & Bradshaw, A. C. (2018) · Cellular Signalling · doi:10.1016/j.cellsig.2018.09.004 · Cited by 122 · see citing works
Reactive Oxygen Species (ROS), Intimal Thickening, and Subclinical Atherosclerotic Disease
Burtenshaw, D., Kitching, M., Redmond, E. M., Megson, I. L., & Cahill, P. A. (2019) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2019.00089 · Cited by 123 · see citing works
Vulnerable Plaque, Characteristics, Detection, and Potential Therapies
Hafiane, A. (2019) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd6030026 · Cited by 124 · see citing works
Cao, G., Xuan, X., Li, Y., Hu, J. H., Zhang, R., Jin, H., & Dong, H. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01120-5 · Cited by 116 · see citing works
Akoumianakis, I., Sanna, F., Margaritis, M., Badi, I., Akawi, N. A., Herdman, L., Coutinho, P., Fagan, H. A., Antonopoulos, A. S., Oikonomou, E. K., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aav5055 · Cited by 97 · see citing works
Translational opportunities of single-cell biology in atherosclerosis
de Winther, M. P. J., Bäck, M., Evans, P. C., Gomez, D. A., Gonçalves, I., Jørgensen, H. F., Koenen, R. R., Lutgens, E., Norata, G. D., Osto, E., et al. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehac686 · Cited by 96 · see citing works
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Steffes, L. C., Froistad, A. A., Andruska, A., Boehm, M., McGlynn, M. N., Zhang, F., Zhang, W., Hou, D., Tian, X., Miquerol, L., et al. (2020) · Circulation · doi:10.1161/circulationaha.120.045750 · Cited by 92 · see citing works
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Vacante, F., Rodor, J., Lalwani, M. K., Mahmoud, A. D., Bennett, M., Pace, A. L. D., Miller, E., van Kuijk, K., de Bruijn, J., Gijbels, M. J., et al. (2021) · Circulation Research · doi:10.1161/circresaha.120.318688 · Cited by 92 · see citing works
Self-citationVascular smooth muscle cell phenotypic switching in atherosclerosis
Yu, Y., Cai, Y., Yang, F., Yang, Y., Cui, Z., Shi, D., & Bai, R. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e37727 · Cited by 96 · see citing works
Osman, I., He, X., Liu, J., Dong, K., Wen, T., Zhang, F., Yu, L., Hu, G., Xin, H., Zhang, W., et al. (2019) · Circulation Research · doi:10.1161/circresaha.118.314187 · Cited by 89 · see citing works
Ni, Z., Deng, J., Potter, C. M. F., Nowak, W. N., Gu, W., Zhang, Z., Chen, T., Chen, Q., Hu, Y., Zhou, B., et al. (2019) · Circulation Research · doi:10.1161/circresaha.119.314855 · Cited by 86 · see citing works
Mußbacher, M., Schossleitner, K., Kral-Pointner, J. B., Salzmann, M., Schrammel, A., & Schmid, J. A. (2022) · Current Atherosclerosis Reports · doi:10.1007/s11883-022-01023-9 · Cited by 86 · see citing works
Xu, X., Zhang, D., Kong, P., Gao, Y., Huang, X.-F., Song, Y., Zhang, W., Guo, R., Li, C., Chen, B., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112869 · Cited by 86 · see citing works
Lee, G.-L., Yeh, C.-C., Wu, J.-Y., Lin, H., Wang, Y., Kuo, Y.-Y., Hsieh, Y.-T., Hsu, Y., & Kuo, C.-C. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.118.311874 · Cited by 84 · see citing works
Efficacy and limitations of senolysis in atherosclerosis
Garrido, A. M., Kaistha, A., Uryga, A. K., Oc, S., Foote, K., Shah, A., Finigan, A., Figg, N., Dobnikar, L., Jørgensen, H., et al. (2022) · Cardiovascular Research · doi:10.1093/cvr/cvab208 · Cited by 83 · see citing works
“example in Myh11-Cre/Rosa26-Confetti mice; flow cytometric sorting of isolated confettiþ cells followed by single cell sequencing (scRNAseq) can then quantify mRNA expression specifically in VSMCs.(14,22) Normal healthy aortas of Myh11-Cre/Rosa26-Confetti mice showed cell clusters corresponding to VSMCs (Myh11þ), adve…”
BackgroundInfluentialSelf-citationTGFβ signaling pathways in human health and disease
Chen, P., Qin, L., & Simons, M. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1113061 · Cited by 84 · see citing works
Connexins: Key Players in the Control of Vascular Plasticity and Function
Pohl, U. (2020) · Physiological Reviews · doi:10.1152/physrev.00010.2019 · Cited by 78 · see citing works
Senescent cells suppress innate smooth muscle cell repair functions in atherosclerosis
Childs, B. G., Zhang, C., Shuja, F., Sturmlechner, I., Trewartha, S., Velasco, R. F., Baker, D. J., Li, H., & van Deursen, J. M. (2021) · Nature Aging · doi:10.1038/s43587-021-00089-5 · Cited by 76 · see citing works
Uryga, A. K., Grootaert, M. O. J., Garrido, A. M., Oc, S., Foote, K., Chappell, J., Finigan, A., Rossiello, F., d’Adda di Fagagna, F., Aravani, D., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-02123-z · Cited by 73 · see citing works
Self-citationA role for collagen type IV in cardiovascular disease?
Steffensen, L. B., & Rasmussen, L. M. (2018) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00070.2018 · Cited by 73 · see citing works
Vendrov, A. E., Stevenson, M., Alahari, S., Pan, H., Wickline, S. A., Madamanchi, N. R., & Runge, M. S. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.117.006775 · Cited by 73 · see citing works
Lineage tracking of origin and fate of smooth muscle cells in atherosclerosis
Bentzon, J. F., & Majesky, M. W. (2017) · Cardiovascular Research · doi:10.1093/cvr/cvx251 · Cited by 72 · see citing works
Li, B., Zang, G., Zhong, W. H., Chen, R., Zhang, Y., Yang, P., & Yan, J. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109593 · Cited by 70 · see citing works
Mechanisms of fibrous cap formation in atherosclerosis
Alonso-Herranz, L., Albarrán-Juárez, J., & Bentzon, J. F. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1254114 · Cited by 72 · see citing works
Novel Insights Regarding Nitric Oxide and Cardiovascular Diseases
Infante, T., Costa, D., & Claudio Napoli, A. (2021) · Angiology · doi:10.1177/0003319720979243 · Cited by 67 · see citing works
Redox control of vascular smooth muscle cell function and plasticity
Durgin, B. G., & Straub, A. C. (2018) · Laboratory Investigation · doi:10.1038/s41374-018-0032-9 · Cited by 69 · see citing works
cGMP Signaling and Vascular Smooth Muscle Cell Plasticity
Lehners, M., Dobrowinski, H., Feil, S. C., & Feil, R. (2018) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd5020020 · Cited by 67 · see citing works
Härdtner, C., Kornemann, J., Krebs, K., Ehlert, C. A., Jander, A., Zou, J., Starz, C., Rauterberg, S., Sharipova, D., Dufner, B., et al. (2020) · Basic Research in Cardiology · doi:10.1007/s00395-020-00838-4 · Cited by 66 · see citing works
Xue, Y., Luo, M., Hu, X., Li, X., Shen, J., Zhu, W., Huang, L., Hu, Y., Guo, Y., Liu, L., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-04255-2 · Cited by 66 · see citing works
Vendrov, A. E., Sumida, A., Canugovi, C., Lozhkin, A. P., Hayami, T., Madamanchi, N. R., & Runge, M. S. (2018) · Redox Biology · doi:10.1016/j.redox.2018.11.021 · Cited by 64 · see citing works
Lim, W., Corden, B., Ng, B., Vanezis, K., D’Agostino, G. A., Widjaja, A. A., Song, W., Xie, C., Su, L., Kwek, X.-Y., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-74944-7 · Cited by 60 · see citing works
Santini, M. P., Malide, D. A., Hoffman, G. E., Pandey, G. S., d’Escamard, V., Nomura-Kitabayashi, A., Rovira, I. I., Kataoka, H., Ochando, J., Harvey, R. P., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2019.12.045 · Cited by 58 · see citing works
Wu, W., Zhang, W., Choi, M., Zhao, J., Gao, P. T., Xue, M., Singer, H. A., Jourd’heuil, D., & Long, X. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101137 · Cited by 62 · see citing works
Harman, J. J., Dobnikar, L., Chappell, J., Stokell, B. G., Dalby, A., Foote, K., Finigan, A. J., Freire-Pritchett, P., Taylor, A. L., Worssam, M. D., et al. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.312765 · Cited by 62 · see citing works
Self-citationNi, H., Haemmig, S., Deng, Y., Chen, J., Simion, V., Yang, D., Sukhova, G. K., Shvartz, E., Wara, A. K., Cheng, H. S., et al. (2021) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.315911 · Cited by 61 · see citing works
Cellular mechanisms of oligoclonal vascular smooth muscle cell expansion in cardiovascular disease
Worssam, M. D., Lambert, J., Oc, S., Taylor, J. C. K., Taylor, A. L., Dobnikar, L., Chappell, J., Harman, J. J., Figg, N. L., Finigan, A. J., et al. (2022) · Cardiovascular Research · doi:10.1093/cvr/cvac138 · Cited by 61 · see citing works
Self-citationCheng, P. P., Wirka, R. C., Kim, J. B., Kim, H.-J., Nguyen, T., Kundu, R. K., Zhao, Q., Sharma, D., Pedroza, A. J., Nagao, M., et al. (2022) · Nature Cardiovascular Research · doi:10.1038/s44161-022-00042-8 · Cited by 61 · see citing works
Immune Mechanisms of Plaque Instability
Gerhardt, T., Haghikia, A., Stapmanns, P., & Leistner, D. M. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.797046 · Cited by 63 · see citing works
Cai, Y., Wen, J., Ma, S., Mai, Z., Zhan, Q., Wang, Y., Zhang, Y., Chen, H., Li, H., Wu, W., et al. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.666449 · Cited by 56 · see citing works
Cho, D. I., Ahn, M. J., Cho, H. H., Cho, M., Jun, J. H., Kang, B. G., Lim, S. Y., Yoo, S. J., Kim, M. R., Kim, H.-S., et al. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-00937-x · Cited by 55 · see citing works
Lipid accumulation and novel insight into vascular smooth muscle cells in atherosclerosis
Liu, Y., Yuan, P.-Z., Wu, J., & Hu, B. (2021) · Journal of Molecular Medicine · doi:10.1007/s00109-021-02109-8 · Cited by 56 · see citing works
Burtenshaw, D., Regan, B., Owen, K., Collins, D. A., MCENEANEY, D. J., Megson, I. L., Redmond, E. M., & Cahill, P. A. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.853451 · Cited by 55 · see citing works
Perivascular cell-specific knockout of the stem cell pluripotency gene Oct4 inhibits angiogenesis
Hess, D. L., Kelly‐Goss, M. R., Cherepanova, O. A., Nguyen, A. T., Baylis, R. A., Tkachenko, S., Annex, B. H., Peirce, S. M., & Owens, G. K. (2019) · Nature Communications · doi:10.1038/s41467-019-08811-z · Cited by 52 · see citing works
van Kuijk, K., Kuppe, C., Betsholtz, C., Vanlandewijck, M., Kramann, R., & Sluimer, J. C. (2019) · Cardiovascular Research · doi:10.1093/cvr/cvz185 · Cited by 52 · see citing works
Silencing Myeloid Netrin-1 Induces Inflammation Resolution and Plaque Regression
Schlegel, M., Sharma, M., Brown, E. J., Newman, A. A. C., Cyr, Y., Afonso, M. S., Corr, E. M., Koelwyn, G. J., Solingen, C. V., Guzman, J., et al. (2021) · Circulation Research · doi:10.1161/circresaha.121.319313 · Cited by 51 · see citing works
Deaton, R. A., Bulut, G. B., Serbulea, V., Salamon, A., Shankman, L. S., Nguyen, A. T., & Owens, G. K. (2022) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.122.318160 · Cited by 51 · see citing works
Knockout rat models mimicking human atherosclerosis created by Cpf1-mediated gene targeting
Lee, J. G., Ha, C. H., Yoon, B., Cheong, S.-A., Kim, G., Lee, D. J., Woo, D., Kim, Y., Nam, S.-Y., Lee, S.-W., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-38732-2 · Cited by 50 · see citing works
Fibrocytes: A Critical Review and Practical Guide
Reinhardt, J. W., & Breuer, C. K. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.784401 · Cited by 42 · see citing works
Erythrocyte Efferocytosis by the Arterial Wall Promotes Oxidation in Early-Stage Atheroma in Humans
Delbosc, S., Bayles, R., Khallou‐Laschet, J., Ollivier, V., Ho‐Tin‐Noé, B., Touat, Z., Deschildre, C., Morvan, M., Louedec, L., Gouya, L., et al. (2017) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2017.00043 · Cited by 45 · see citing works
Worssam, M. D., & Jørgensen, H. F. (2021) · Biochemical Society Transactions · doi:10.1042/bst20210138 · Cited by 44 · see citing works
Self-citationDiRenzo, D. M., Owens, G. K., & Leeper, N. J. (2017) · Circulation Research · doi:10.1161/circresaha.116.310091 · Cited by 44 · see citing works
Cao, K., Zhang, T., Li, Z., Song, M., Li, A., Yan, J., Guo, S., Wang, L., Huang, S., Li, Z., et al. (2023) · The Journal of Pathology · doi:10.1002/path.6052 · Cited by 44 · see citing works
Gong, X., Liu, Y., Liu, H., Cao, N., Zeng, L., Tian, M., Zeng, C., Hu, Y., Zhang, R., Chen, Y., et al. (2024) · Theranostics · doi:10.7150/thno.87201 · Cited by 43 · see citing works
Smooth Muscle Heterogeneity and Plasticity in Health and Aortic Aneurysmal Disease
Hu, Y., Cai, Z., & He, B. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411701 · Cited by 42 · see citing works
An update on ox-LDL-inducing vascular smooth muscle cell-derived foam cells in atherosclerosis
Guo, J., & Du, L. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1481505 · Cited by 44 · see citing works
Smooth muscle cells in atherosclerosis: essential but overlooked translational perspectives
Azar, P., Jarr, K.-U., Gomez, D. A., Jørgensen, H. F., Leeper, N. J., & Bochaton‐Piallat, M. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf337 · Cited by 45 · see citing works
Self-citationAdult Stem Cells in Vascular Remodeling
Wang, D., Li, L. K., Dai, T., Wang, A.-J., & Li, S. (2018) · Theranostics · doi:10.7150/thno.19577 · Cited by 42 · see citing works
Yao, D., Xu, L., Xu, O., Li, R., Chen, M., Shen, H., Zhu, H., Zhang, F., Yao, D., Chen, Y.-F., et al. (2018) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.117.310468 · Cited by 41 · see citing works
Lacey, M. R., Baribault, C., Ehrlich, K. C., & Ehrlich, M. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.11.031 · Cited by 41 · see citing works
- Authors
- Chappell, J., Harman, J. L., Narasimhan, V. M., Yu, H., Foote, K., Simons, B. D., Bennett, M. R., & Jørgensen, H. F.
- Affiliations
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- From the Cardiovascular Medicine Division, Department of Medicine (J.C., J.L.H., H.Y., K.F., M.R.B., H.F.J.), Cavendish Laboratory, Department of Physics (B.D.S.), The Wellcome Trust/Cancer Research UK Gurdon Institute (B.D.S.), and Wellcome Trust-Medical Research Council Stem Cell Institute (B.D.S.), University of Cambridge, United Kingdom; and The Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom (V.M.N.).
- Corresponding author
- Jørgensen, Helle F.
- ORCID
- Venue
- Circulation Research
- Published
- 2016-12-09
- Volume
- 119
- Issue
- 12
- Pages
- 1313-1323
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC5149073
- OpenAlex
- W2525459565
- Cited by
- 437
- References
- 32
- Citations by year
- 2026: 39 · 2025: 38 · 2024: 45 · 2023: 56 · 2022: 62 · 2021: 62 · 2020: 39 · 2019: 45 · 2018: 29 · 2017: 17 · 2016: 3
- FWCI
- 18.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Circulation Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- Wellcome Trust (098357/Z/12/Z, 100574/Z/12/Z)
- British Heart Foundation (PG/13/25/30014, PG/16/11/32021, PG/12/86/29930, RM/13/3/30159, RG/13/14/30314, FS/15/38/31516, RE/13/6/30180)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cerebrovascular and Carotid Artery Diseases
- Keywords
- vascular smooth muscle cells, vascular smooth muscle cell proliferation, phenotypic plasticity, intimal hyperplasia, atherosclerosis, atherosclerotic plaque, lineage tracing, alpha-smooth muscle actin, VSMC migration, vascular injury
- MeSH terms
- Animals, Disease Models, Animal, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Muscle, Smooth, Vascular, Mice, Knockout, Myocytes, Smooth Muscle, Cell Proliferation, Atherosclerosis, Mice, Vascular System Injuries, Neointima
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