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Cardiovasc. Med."],"abstract":"<jats:p>Atherosclerosis, the fundamental pathological basis of most cardiovascular diseases which remain the leading cause of global mortality, is driven by both lipid accumulation and dynamic cellular reprogramming within the vessel wall. Central to this process is the remarkable phenotypic plasticity of vascular smooth muscle cells (VSMCs). Far from being terminally differentiated, VSMCs undergo profound transitions from a contractile state to diverse states, including synthetic, macrophage-like, foam cell-like, and fibroblast-like states, which critically influence plaque formation, stability, and rupture. This review synthesizes the multilayered molecular mechanisms governing VSMC plasticity, encompassing transcriptional networks, epigenetic reprogramming, and microenvironmental cues. Moreover, this review highlights recent breakthroughs enabled by single-cell omics and lineage tracing, that have revealed unprecedented heterogeneity and clonal expansion of VSMCs within atherosclerotic lesions. Furthermore, we explore the translational potential of targeting VSMC plasticity, and discuss emerging strategies, including phenotype-specific modulation, immunotherapy, nanomedicine, and senotherapeutics. Finally, we outline future directions focused on dynamic regulatory networks, spatial pathophysiology, and the integration of aging biology to advance precision medicine in atherosclerosis. In summary, VSMC phenotypic plasticity is a core mechanism underlying the initiation and progression of atherosclerosis. Precise modulation of this process holds promise for overcoming current therapeutic limitations and driving a paradigm shift toward mechanism-guided personalized therapy for cardiovascular diseases.<\/jats:p>","DOI":"10.31083\/rcm50363","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:17:46Z","timestamp":1788437866000},"source":"Crossref","is-referenced-by-count":1,"title":["Vascular Smooth Muscle Cell Plasticity in Atherosclerosis: Mechanisms, Recent Advances, and Therapeutic Implications"],"prefix":"10.31083","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3095-2155","authenticated-orcid":true,"given":"Tianhan","family":"Li","sequence":"first","affiliation":[{"name":"School of Basic Medicine, Henan Medical University, 453003 Xinxiang, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4435-7164","authenticated-orcid":true,"given":"Xinyao","family":"Niu","sequence":"additional","affiliation":[{"name":"School of Medical Technology, Henan Medical University, 453003 Xinxiang, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5342-2720","authenticated-orcid":true,"given":"Liaoxun","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Medical Technology, Henan Medical University, 453003 Xinxiang, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9174-4037","authenticated-orcid":true,"given":"Yinming","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Medical Technology, Henan Medical University, 453003 Xinxiang, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7810-9941","authenticated-orcid":true,"given":"Lichen","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medical Technology, Henan Medical University, 453003 Xinxiang, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Engelen SE, Robinson AJB, Zurke YX, Monaco C. Therapeutic strategies targeting inflammation and immunity in atherosclerosis: how to proceed? Nature Reviews. Cardiology. 2022; 19: 522\u2013542.","DOI":"10.1038\/s41569-021-00668-4"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Soehnlein O, Libby P. Targeting inflammation in atherosclerosis - from experimental insights to the clinic. Nature Reviews. Drug Discovery. 2021; 20: 589\u2013610.","DOI":"10.1038\/s41573-021-00198-1"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Alencar GF, Owsiany KM, Karnewar S, Sukhavasi K, Mocci G, Nguyen AT, et al. Stem Cell Pluripotency Genes Klf4 and Oct4 Regulate Complex SMC Phenotypic Changes Critical in Late-Stage Atherosclerotic Lesion Pathogenesis. Circulation. 2020; 142: 2045\u20132059.","DOI":"10.1161\/CIRCULATIONAHA.120.046672"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Pan H, Ho SE, Xue C, Cui J, Johanson QS, Sachs N, et al. Atherosclerosis Is a Smooth Muscle Cell-Driven Tumor-Like Disease. Circulation. 2024; 149: 1885\u20131898.","DOI":"10.1161\/CIRCULATIONAHA.123.067587"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Miano JM, Fisher EA, Majesky MW. Fate and State of Vascular Smooth Muscle Cells in Atherosclerosis. Circulation. 2021; 143: 2110\u20132116.","DOI":"10.1161\/CIRCULATIONAHA.120.049922"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Bennett MR, Sinha S, Owens GK. Vascular Smooth Muscle Cells in Atherosclerosis. Circulation Research. 2016; 118: 692\u2013702.","DOI":"10.1161\/CIRCRESAHA.115.306361"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Touyz RM, Alves-Lopes R, Rios FJ, Camargo LL, Anagnostopoulou A, Arner A, et al. Vascular smooth muscle contraction in hypertension. Cardiovascular Research. 2018; 114: 529\u2013539.","DOI":"10.1093\/cvr\/cvy023"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Grootaert MOJ, Bennett MR. Vascular smooth muscle cells in atherosclerosis: time for a re-assessment. Cardiovascular Research. 2021; 117: 2326\u20132339.","DOI":"10.1093\/cvr\/cvab046"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Lambert J, J\u00f8rgensen HF. Vascular smooth muscle cell phenotypic switching and plaque stability: a role for CHI3L1. Cardiovascular Research. 2021; 117: 2691\u20132693.","DOI":"10.1093\/cvr\/cvab099"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Zhao X, Tian J, Ye Z, Xu M, Song X, Huang R. Evaluation of Therapeutic Agents Targeting the Pathogenesis of Coronary Artery Spasm: A Mini Review. Current Vascular Pharmacology. 2021; 19: 347\u2013358.","DOI":"10.2174\/1570161118666200603131119"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Cao G, Xuan X, Hu J, Zhang R, Jin H, Dong H. How vascular smooth muscle cell phenotype switching contributes to vascular disease. Cell Communication and Signaling: CCS. 2022; 20: 180.","DOI":"10.1186\/s12964-022-00993-2"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Pagiatakis C, Sun D, Tobin SW, Miyake T, McDermott JC. TGF\u03b2-TAZ\/SRF signalling regulates vascular smooth muscle cell differentiation. The FEBS Journal. 2017; 284: 1644\u20131656.","DOI":"10.1111\/febs.14070"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Munshaw S, Bruche S, Redpath AN, Jones A, Patel J, Dub\u00e9 KN, et al. Thymosin \u03b24 protects against aortic aneurysm via endocytic regulation of growth factor signaling. The Journal of Clinical Investigation. 2021; 131: e127884.","DOI":"10.1172\/JCI127884"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Xing M, Chen W, Ji Y, Song W. SLC44A2-mediated phenotypic switch of vascular smooth muscle cells contributes to aortic aneurysm. The Journal of Clinical Investigation. 2024; 134: e183527.","DOI":"10.1172\/JCI183527"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Hamczyk MR, Nevado RM, Gonzalo P, Andr\u00e9s-Manzano MJ, Nogales P, Quesada V, et al. Endothelial-to-Mesenchymal Transition Contributes to Accelerated Atherosclerosis in Hutchinson-Gilford Progeria Syndrome. Circulation. 2024; 150: 1612\u20131630.","DOI":"10.1161\/CIRCULATIONAHA.123.065768"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Da X, Li Z, Huang X, He Z, Yu Y, Tian T, et al. AGGF1 therapy inhibits thoracic aortic aneurysms by enhancing integrin \u03b17-mediated inhibition of TGF-\u03b21 maturation and ERK1\/2 signaling. Nature Communications. 2023; 14: 2265.","DOI":"10.1038\/s41467-023-37809-x"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Yap C, Mieremet A, de Vries CJM, Micha D, de Waard V. Six Shades of Vascular Smooth Muscle Cells Illuminated by KLF4 (Kr\u00fcppel-Like Factor 4). 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Nature Communications. 2024; 15: 6919.","DOI":"10.1038\/s41467-024-51350-5"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Su C, Liu M, Yao X, Hao W, Ma J, Ren Y, et al. Vascular injury activates the ELK1\/SND1\/SRF pathway to promote vascular smooth muscle cell proliferative phenotype and neointimal hyperplasia. Cellular and Molecular Life Sciences: CMLS. 2024; 81: 59.","DOI":"10.1007\/s00018-023-05095-x"},{"key":"ref28","unstructured":"Saggini R, Pellegrino R. MAPK is implicated in sepsis, immunity, and inflammation. International Journal of Infection. 2024; 8: 100\u2013104."},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Wei Z, Chong H, Jiang Q, Tang Y, Xu J, Wang H, et al. Smooth Muscle Overexpression of PGC1\u03b1 Attenuates Atherosclerosis in Rabbits. Circulation Research. 2021; 129: e72\u2013e86.","DOI":"10.1161\/CIRCRESAHA.120.317705"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Xu Q. Biomechanical-stress-induced signaling and gene expression in the development of arteriosclerosis. Trends in Cardiovascular Medicine. 2000; 10: 35\u201341.","DOI":"10.1016\/s1050-1738(00)00042-6"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Zhang H, Lin L, Yang A, Liang Y, Huang B. Scutellarin alleviates tensile stress-induced proliferation and migration of venous smooth muscle cells via mediating the p38 MAPK pathway. Tissue & Cell. 2024; 87: 102300.","DOI":"10.1016\/j.tice.2024.102300"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Li J, Li X, Song S, Sun Z, Li Y, Yang L, et al. Mitochondria spatially and temporally modulate VSMC phenotypes via interacting with cytoskeleton in cardiovascular diseases. Redox Biology. 2023; 64: 102778.","DOI":"10.1016\/j.redox.2023.102778"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Zhang T, Cao RJ, Niu JL, Chen ZH, Mu SQ, Cao T, et al. G6PD maintains the VSMC synthetic phenotype and accelerates vascular neointimal hyperplasia by inhibiting the VDAC1-Bax-mediated mitochondrial apoptosis pathway. Cellular & Molecular Biology Letters. 2024; 29: 47.","DOI":"10.1186\/s11658-024-00566-w"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Jia Y, Mao C, Ma Z, Huang J, Li W, Ma X, et al. PHB2 Maintains the Contractile Phenotype of VSMCs by Counteracting PKM2 Splicing. Circulation Research. 2022; 131: 807\u2013824.","DOI":"10.1161\/CIRCRESAHA.122.321005"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Fu Z, Yang S, Chang X, Liu P, Wang Y. Vascular smooth muscle cell metabolic reprogramming and phenotypic remodeling in atherosclerosis. Cell Death Discovery. 2025; 12: 64.","DOI":"10.1038\/s41420-025-02932-9"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Yu Y, Cai Y, Yang F, Yang Y, Cui Z, Shi D, et al. Vascular smooth muscle cell phenotypic switching in atherosclerosis. Heliyon. 2024; 10: e37727.","DOI":"10.1016\/j.heliyon.2024.e37727"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Zhang Y, Sun L, Li F, Li Y, Zhou Q. Paeoniflorin suppresses the phenotypic transformation of vascular smooth muscle cells during atherosclerosis by regulating the MAPK\/NF-\u03baB pathways and ABCA1 expression. Cellular Signalling. 2026; 143: 112477.","DOI":"10.1016\/j.cellsig.2026.112477"},{"key":"ref38","unstructured":"Avivar-Valderas A. Inhibition of PI3K\u03b2 and mTOR influence the immune response and the defense mechanism against pathogens. International Journal of Infection. 2023; 7: 46\u201349."},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Su WY, Tian LY, Guo LP, Huang LQ, Gao WY. PI3K signaling-regulated metabolic reprogramming: From mechanism to application. Biochimica et biophysica acta. Reviews on cancer. 2023; 1878: 188952.","DOI":"10.1016\/j.bbcan.2023.188952"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Shu Z, Li X, Zhang W, Huyan Z, Cheng D, Xie S, et al. MG-132 activates sodium palmitate-induced autophagy in human vascular smooth muscle cells and inhibits senescence via the PI3K\/AKT\/mTOR axis. Lipids in Health and Disease. 2024; 23: 282.","DOI":"10.1186\/s12944-024-02268-w"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Zhu N, Guo ZF, Kazama K, Yi B, Tongmuang N, Yao H, et al. Epigenetic regulation of vascular smooth muscle cell phenotypic switch and neointimal formation by PRMT5. Cardiovascular Research. 2023; 119: 2244\u20132255.","DOI":"10.1093\/cvr\/cvad110"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Yorn C, Kim H, Jeong K. Influence of DNA Methylation on Vascular Smooth Muscle Cell Phenotypic Switching. International Journal of Molecular Sciences. 2024; 25: 3136.","DOI":"10.3390\/ijms25063136"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"Chakraborty R, Ostriker AC, Xie Y, Dave JM, Gamez-Mendez A, Chatterjee P, et al. Histone Acetyltransferases p300 and CBP Coordinate Distinct Chromatin Remodeling Programs in Vascular Smooth Muscle Plasticity. Circulation. 2022; 145: 1720\u20131737.","DOI":"10.1161\/CIRCULATIONAHA.121.057599"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"Ni H, Haemmig S, Deng Y, Chen J, Simion V, Yang D, et al. A Smooth Muscle Cell-Enriched Long Noncoding RNA Regulates Cell Plasticity and Atherosclerosis by Interacting With Serum Response Factor. Arteriosclerosis, Thrombosis, and Vascular Biology. 2021; 41: 2399\u20132416.","DOI":"10.1161\/ATVBAHA.120.315911"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Lin JJ, Chen R, Yang LY, Gong M, Du MY, Mu SQ, et al. Hsa_circ_0001402 alleviates vascular neointimal hyperplasia through a miR-183-5p-dependent regulation of vascular smooth muscle cell proliferation, migration, and autophagy. Journal of Advanced Research. 2024; 60: 93\u2013110.","DOI":"10.1016\/j.jare.2023.07.010"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Boettger T, Beetz N, Kostin S, Schneider J, Kr\u00fcger M, Hein L, et al. Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143\/145 gene cluster. The Journal of Clinical Investigation. 2009; 119: 2634\u20132647.","DOI":"10.1172\/JCI38864"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"Alexander MR, Owens GK. Epigenetic control of smooth muscle cell differentiation and phenotypic switching in vascular development and disease. Annual Review of Physiology. 2012; 74: 13\u201340.","DOI":"10.1146\/annurev-physiol-012110-142315"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"Liu ZL, Li Y, Lin YJ, Shi MM, Fu MX, Li ZQ, et al. Aging aggravates aortic aneurysm and dissection via miR-1204-MYLK signaling axis in mice. Nature Communications. 2024; 15: 5985.","DOI":"10.1038\/s41467-024-50036-2"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"Maegdefessel L, Fasolo F. Long Non-Coding RNA Function in Smooth Muscle Cell Plasticity and Atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology. 2025; 45: 172\u2013185.","DOI":"10.1161\/ATVBAHA.124.320393"},{"key":"ref50","doi-asserted-by":"publisher","unstructured":"Fasolo F, Paloschi V, Maegdefessel L. Long non-coding RNAs at the crossroad of vascular smooth muscle cell phenotypic modulation in atherosclerosis and neointimal formation. Atherosclerosis. 2023; 374: 34\u201343.","DOI":"10.1016\/j.atherosclerosis.2022.11.021"},{"key":"ref51","doi-asserted-by":"publisher","unstructured":"Terriaca S, Ferlosio A, Scioli MG, Coppa F, Bertoldo F, Pisano C, et al. miRNA Regulation of Cell Phenotype and Parietal Remodeling in Atherosclerotic and Non-Atherosclerotic Aortic Aneurysms: Differences and Similarities. International Journal of Molecular Sciences. 2024; 25: 2641.","DOI":"10.3390\/ijms25052641"},{"key":"ref52","doi-asserted-by":"publisher","unstructured":"Rodor J, Klimi E, Brown SD, Krilis G, Braga L, Ring NAR, et al. Functional screening identifies miRNAs with a novel function inhibiting vascular smooth muscle cell proliferation. Molecular Therapy: the Journal of the American Society of Gene Therapy. 2025; 33: 615\u2013630.","DOI":"10.1016\/j.ymthe.2024.12.037"},{"key":"ref53","doi-asserted-by":"publisher","unstructured":"Ashraf JV, Al Haj Zen A. Role of Vascular Smooth Muscle Cell Phenotype Switching in Arteriogenesis. International Journal of Molecular Sciences. 2021; 22: 10585.","DOI":"10.3390\/ijms221910585"},{"key":"ref54","doi-asserted-by":"publisher","unstructured":"M\u00e9ndez-Barbero N, Guti\u00e9rrez-Mu\u00f1oz C, Blanco-Colio LM. Cellular Crosstalk between Endothelial and Smooth Muscle Cells in Vascular Wall Remodeling. International Journal of Molecular Sciences. 2021; 22: 7284.","DOI":"10.3390\/ijms22147284"},{"key":"ref55","doi-asserted-by":"publisher","unstructured":"Wang X, Li H, Zhang Y, Liu Q, Sun X, He X, et al. Suppression of miR-4463 promotes phenotypic switching in VSMCs treated with Ox-LDL. Cell and Tissue Research. 2021; 383: 1155\u20131165.","DOI":"10.1007\/s00441-020-03338-y"},{"key":"ref56","doi-asserted-by":"publisher","unstructured":"Li S, Cao S, Li P, Zhang F, Ren G, Wang X, et al. Endothelial BMP6 Drives Hemodynamic-Dependent VSMCs Calcification in Carotid Atherosclerosis. Advanced Science (Weinheim, Baden-Wurttemberg, Germany). 2026; 13: e02801.","DOI":"10.1002\/advs.202502801"},{"key":"ref57","doi-asserted-by":"publisher","unstructured":"Liu X, Zheng T, Zhang Y, Zhao Y, Liu F, Dai S, et al. Endothelial Dickkopf-1 Promotes Smooth Muscle Cell-derived Foam Cell Formation via USP53-mediated Deubiquitination of SR-A During Atherosclerosis. International Journal of Biological Sciences. 2024; 20: 2943\u20132964.","DOI":"10.7150\/ijbs.91957"},{"key":"ref58","doi-asserted-by":"publisher","unstructured":"Zheng G, Zhao Y, Li Z, Hua Y, Zhang J, Miao Y, et al. GLSP and GLSP-derived triterpenes attenuate atherosclerosis and aortic calcification by stimulating ABCA1\/G1-mediated macrophage cholesterol efflux and inactivating RUNX2-mediated VSMC osteogenesis. Theranostics. 2023; 13: 1325\u20131341.","DOI":"10.7150\/thno.80250"},{"key":"ref59","doi-asserted-by":"publisher","unstructured":"Tan J, Liang Y, Yang Z, He Q, Tong J, Deng Y, et al. Single-Cell Transcriptomics Reveals Crucial Cell Subsets and Functional Heterogeneity Associated With Carotid Atherosclerosis and Cerebrovascular Events. Arteriosclerosis, Thrombosis, and Vascular Biology. 2023; 43: 2312\u20132332.","DOI":"10.1161\/ATVBAHA.123.318974"},{"key":"ref60","doi-asserted-by":"publisher","unstructured":"Beck-Joseph J, Tabrizian M, Lehoux S. Molecular Interactions Between Vascular Smooth Muscle Cells and Macrophages in Atherosclerosis. Frontiers in Cardiovascular Medicine. 2021; 8: 737934.","DOI":"10.3389\/fcvm.2021.737934"},{"key":"ref61","doi-asserted-by":"publisher","unstructured":"Robichaud S, Rasheed A, Pietrangelo A, Doyoung Kim A, Boucher DM, Emerton C, et al. Autophagy Is Differentially Regulated in Leukocyte and Nonleukocyte Foam Cells During Atherosclerosis. Circulation Research. 2022; 130: 831\u2013847.","DOI":"10.1161\/CIRCRESAHA.121.320047"},{"key":"ref62","doi-asserted-by":"publisher","unstructured":"Yin Z, Zhang J, Zhao M, Liu J, Xu Y, Peng S, et al. EDIL3\/Del-1 prevents aortic dissection through enhancing internalization and degradation of apoptotic vascular smooth muscle cells. Autophagy. 2024; 20: 2405\u20132425.","DOI":"10.1080\/15548627.2024.2367191"},{"key":"ref63","doi-asserted-by":"publisher","unstructured":"Weih F, Gr\u00e4bner R, Hu D, Beer M, Habenicht AJR. Control of dichotomic innate and adaptive immune responses by artery tertiary lymphoid organs in atherosclerosis. Frontiers in Physiology. 2012; 3: 226.","DOI":"10.3389\/fphys.2012.00226"},{"key":"ref64","doi-asserted-by":"publisher","unstructured":"Pan H, Xue C, Auerbach BJ, Fan J, Bashore AC, Cui J, et al. 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Metabolites. 2025; 15: 243.","DOI":"10.3390\/metabo15040243"},{"key":"ref74","doi-asserted-by":"publisher","unstructured":"Mohmand-Borkowski A, Rozmyslowicz T. Immunohistochemical Localization of Fibroblast Activation Protein in Coronary Arteries with Different Forms of Atherosclerosis. Metabolites. 2024; 14: 573.","DOI":"10.3390\/metabo14110573"},{"key":"ref75","doi-asserted-by":"publisher","unstructured":"Meletta R, M\u00fcller Herde A, Chiotellis A, Isa M, Rancic Z, Borel N, et al. Evaluation of the radiolabeled boronic acid-based FAP inhibitor MIP-1232 for atherosclerotic plaque imaging. Molecules (Basel, Switzerland). 2015; 20: 2081\u20132099.","DOI":"10.3390\/molecules20022081"},{"key":"ref76","doi-asserted-by":"publisher","unstructured":"Wang Y, Nanda V, Direnzo D, Ye J, Xiao S, Kojima Y, et al. Clonally expanding smooth muscle cells promote atherosclerosis by escaping efferocytosis and activating the complement cascade. 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Diverse cellular architecture of atherosclerotic plaque derives from clonal expansion of a few medial SMCs. JCI Insight. 2017; 2: e95890.","DOI":"10.1172\/jci.insight.95890"},{"key":"ref83","doi-asserted-by":"publisher","unstructured":"Luo L, Fu C, Bell CF, Wang Y, Leeper NJ. Role of vascular smooth muscle cell clonality in atherosclerosis. Frontiers in Cardiovascular Medicine. 2023; 10: 1273596.","DOI":"10.3389\/fcvm.2023.1273596"},{"key":"ref84","doi-asserted-by":"publisher","unstructured":"Worssam MD, Lambert J, Oc S, Taylor JCK, Taylor AL, Dobnikar L, et al. Cellular mechanisms of oligoclonal vascular smooth muscle cell expansion in cardiovascular disease. Cardiovascular Research. 2023; 119: 1279\u20131294.","DOI":"10.1093\/cvr\/cvac138"},{"key":"ref85","doi-asserted-by":"publisher","unstructured":"Lin A, Brittan M, Baker AH, Dimmeler S, Fisher EA, Sluimer JC, et al. Clonal Expansion in Cardiovascular Pathology. JACC. 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Age-associated proinflammatory secretory phenotype in vascular smooth muscle cells from the non-human primate Macaca mulatta: reversal by resveratrol treatment. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2012; 67: 811\u2013820.","DOI":"10.1093\/gerona\/glr228"},{"key":"ref89","doi-asserted-by":"publisher","unstructured":"Xu X, Zhang DD, Kong P, Gao YK, Huang XF, Song Y, et al. Sox10 escalates vascular inflammation by mediating vascular smooth muscle cell transdifferentiation and pyroptosis in neointimal hyperplasia. Cell Reports. 2023; 42: 112869.","DOI":"10.1016\/j.celrep.2023.112869"},{"key":"ref90","doi-asserted-by":"publisher","unstructured":"G\u0142uchowska A, Cysewski D, Baj-Krzyworzeka M, Szatanek R, W\u0119glarczyk K, Podszywa\u0142ow-Bartnicka P, et al. Unbiased proteomic analysis of extracellular vesicles secreted by senescent human vascular smooth muscle cells reveals their ability to modulate immune cell functions. GeroScience. 2022; 44: 2863\u20132884.","DOI":"10.1007\/s11357-022-00625-0"},{"key":"ref91","doi-asserted-by":"publisher","unstructured":"Gadecka A, Koblowska M, Kossowska H, Iwanicka-Nowicka R, Janiszewska D, Mosieniak G, et al. Senescence-associated alterations in histone H3 modifications, HP1 alpha levels and distribution, and in the transcriptome of vascular smooth muscle cells in different types of senescence. Cell Communication and Signaling: CCS. 2025; 23: 321.","DOI":"10.1186\/s12964-025-02315-8"},{"key":"ref92","doi-asserted-by":"publisher","unstructured":"Li X, Chen M, Chen X, He X, Li X, Wei H, et al. TRAP1 drives smooth muscle cell senescence and promotes atherosclerosis via HDAC3-primed histone H4 lysine 12 lactylation. European Heart Journal. 2024; 45: 4219\u20134235.","DOI":"10.1093\/eurheartj\/ehae379"},{"key":"ref93","doi-asserted-by":"publisher","unstructured":"Ma W, Jia K, Cheng H, Xu H, Li Z, Zhang H, et al. Orphan Nuclear Receptor NR4A3 Promotes Vascular Calcification via Histone Lactylation. Circulation Research. 2024; 134: 1427\u20131447.","DOI":"10.1161\/CIRCRESAHA.123.323699"},{"key":"ref94","doi-asserted-by":"publisher","unstructured":"Grootaert MOJ, Finigan A, Figg NL, Uryga AK, Bennett MR. SIRT6 Protects Smooth Muscle Cells From Senescence and Reduces Atherosclerosis. Circulation Research. 2021; 128: 474\u2013491.","DOI":"10.1161\/CIRCRESAHA.120.318353"},{"key":"ref95","doi-asserted-by":"publisher","unstructured":"Childs BG, Zhang C, Shuja F, Sturmlechner I, Trewartha S, Fierro Velasco R, et al. Senescent cells suppress innate smooth muscle cell repair functions in atherosclerosis. Nature Aging. 2021; 1: 698\u2013714.","DOI":"10.1038\/s43587-021-00089-5"},{"key":"ref96","doi-asserted-by":"publisher","unstructured":"Wang J, Uryga AK, Reinhold J, Figg N, Baker L, Finigan A, et al. Vascular Smooth Muscle Cell Senescence Promotes Atherosclerosis and Features of Plaque Vulnerability. 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Atherosclerosis. 2025; 403: 119176.","DOI":"10.1016\/j.atherosclerosis.2025.119176"},{"key":"ref100","doi-asserted-by":"publisher","unstructured":"Tai S, Sun J, Zhou Y, Zhu Z, He Y, Chen M, et al. Metformin suppresses vascular smooth muscle cell senescence by promoting autophagic flux. Journal of Advanced Research. 2022; 41: 205\u2013218.","DOI":"10.1016\/j.jare.2021.12.009"},{"key":"ref101","doi-asserted-by":"publisher","unstructured":"Sung JY, Kim SG, Park SY, Kim JR, Choi HC. Telomere stabilization by metformin mitigates the progression of atherosclerosis via the AMPK-dependent p-PGC-1\u03b1 pathway. Experimental & Molecular Medicine. 2024; 56: 1967\u20131979.","DOI":"10.1038\/s12276-024-01297-w"},{"key":"ref102","doi-asserted-by":"publisher","unstructured":"Gadecka A, Nowak N, Bulanda E, Janiszewska D, Dudkowska M, Sikora E, et al. The senolytic cocktail, dasatinib and quercetin, impacts the chromatin structure of both young and senescent vascular smooth muscle cells. GeroScience. 2025; 47: 3907\u20133925.","DOI":"10.1007\/s11357-024-01504-6"},{"key":"ref103","doi-asserted-by":"publisher","unstructured":"Razazian M, Bahiraii S, Sohail A, Mandl M, Jannat I, Beilhack G, et al. Fisetin ameliorates vascular smooth muscle cell calcification via DUSP1-dependent p38 MAPK inhibition. Aging. 2025; 17: 885\u2013907.","DOI":"10.18632\/aging.206233"},{"key":"ref104","doi-asserted-by":"publisher","unstructured":"Kim SG, Sung JY, Kang YJ, Choi HC. PPAR\u03b3 activation by fisetin mitigates vascular smooth muscle cell senescence via the mTORC2-FoxO3a-autophagy signaling pathway. Biochemical Pharmacology. 2023; 218: 115892.","DOI":"10.1016\/j.bcp.2023.115892"},{"key":"ref105","doi-asserted-by":"publisher","unstructured":"Faleeva M, Ahmad S, Theofilatos K, Lynham S, Watson G, Whitehead M, et al. Sox9 Accelerates Vascular Aging by Regulating Extracellular Matrix Composition and Stiffness. Circulation Research. 2024; 134: 307\u2013324.","DOI":"10.1161\/CIRCRESAHA.123.323365"},{"key":"ref106","doi-asserted-by":"publisher","unstructured":"Chen P, Hong W, Chen Z, Gordillo-Martinez F, Wang S, Fan H, et al. CCAAT\/Enhancer-Binding Protein Alpha Is a Novel Regulator of Vascular Smooth Muscle Cell Osteochondrogenic Transition and Vascular Calcification. Frontiers in Physiology. 2022; 13: 755371.","DOI":"10.3389\/fphys.2022.755371"},{"key":"ref107","doi-asserted-by":"publisher","unstructured":"Cherepanova OA, Gomez D, Shankman LS, Swiatlowska P, Williams J, Sarmento OF, et al. Activation of the pluripotency factor OCT4 in smooth muscle cells is atheroprotective. Nature Medicine. 2016; 22: 657\u2013665.","DOI":"10.1038\/nm.4109"},{"key":"ref108","doi-asserted-by":"publisher","unstructured":"Domenga V, Fardoux P, Lacombe P, Monet M, Maciazek J, Krebs LT, et al. Notch3 is required for arterial identity and maturation of vascular smooth muscle cells. Genes & Development. 2004; 18: 2730\u20132735.","DOI":"10.1101\/gad.308904"},{"key":"ref109","doi-asserted-by":"publisher","unstructured":"Lepore JJ, Cheng L, Min Lu M, Mericko PA, Morrisey EE, Parmacek MS, et al. High-efficiency somatic mutagenesis in smooth muscle cells and cardiac myocytes in SM22alpha-Cre transgenic mice. Genesis. 2005; 41: 179\u2013184.","DOI":"10.1002\/gene.20112"},{"key":"ref110","doi-asserted-by":"publisher","unstructured":"Warthi G, Faulkner JL, Doja J, Ghanam AR, Gao P, Yang AC, et al. Generation and Comparative Analysis of an Itga8-CreERT2 Mouse with Preferential Activity in Vascular Smooth Muscle Cells. Nature Cardiovascular Research. 2022; 1: 1084\u20131100.","DOI":"10.1038\/s44161-022-00162-1"},{"key":"ref111","doi-asserted-by":"publisher","unstructured":"Wirth A, Beny\u00f3 Z, Lukasova M, Leutgeb B, Wettschureck N, Gorbey S, et al. G12-G13-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension. Nature Medicine. 2008; 14: 64\u201368.","DOI":"10.1038\/nm1666"},{"key":"ref112","doi-asserted-by":"crossref","unstructured":"Miwa T, Koyama T, Shirai M. Muscle specific expression of Cre recombinase under two actin promoters in transgenic mice. Genesis (New York, N.Y.: 2000). 2000; 26: 136\u2013138.","DOI":"10.1002\/(SICI)1526-968X(200002)26:2<136::AID-GENE11>3.0.CO;2-J"},{"key":"ref113","doi-asserted-by":"publisher","unstructured":"Chakraborty R, Chatterjee P, Dave JM, Ostriker AC, Greif DM, Rzucidlo EM, et al. Targeting smooth muscle cell phenotypic switching in vascular disease. JVS-vascular Science. 2021; 2: 79\u201394.","DOI":"10.1016\/j.jvssci.2021.04.001"},{"key":"ref114","doi-asserted-by":"publisher","unstructured":"He J, Gao Y, Yang C, Guo Y, Liu L, Lu S, et al. Navigating the landscape: Prospects and hurdles in targeting vascular smooth muscle cells for atherosclerosis diagnosis and therapy. Journal of Controlled Release: Official Journal of the Controlled Release Society. 2024; 366: 261\u2013281.","DOI":"10.1016\/j.jconrel.2023.12.047"},{"key":"ref115","doi-asserted-by":"publisher","unstructured":"Ma S, Motevalli SM, Chen J, Xu MQ, Wang Y, Feng J, et al. Precise theranostic nanomedicines for inhibiting vulnerable atherosclerotic plaque progression through regulation of vascular smooth muscle cell phenotype switching. Theranostics. 2018; 8: 3693\u20133706.","DOI":"10.7150\/thno.24364"},{"key":"ref116","doi-asserted-by":"publisher","unstructured":"Wu JH, Liu YX, Zong JB, Qiu M, Zhou YF, Li YN, et al. TTK Inhibition Alleviates Postinjury Neointimal Formation and Atherosclerosis. Advanced Science (Weinheim, Baden-Wurttemberg, Germany). 2025; 12: e2409250.","DOI":"10.1002\/advs.202409250"},{"key":"ref117","doi-asserted-by":"publisher","unstructured":"Yang S, Zhao Y, Cao S, Liu X, Feng M, Chen Y, et al. Kanglexin counters vascular smooth muscle cell dedifferentiation and associated arteriosclerosis through inhibiting PDGFR. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology. 2024; 130: 155704.","DOI":"10.1016\/j.phymed.2024.155704"},{"key":"ref118","doi-asserted-by":"publisher","unstructured":"Cho DI, Ahn MJ, Cho HH, Cho M, Jun JH, Kang BG, et al. ANGPTL4 stabilizes atherosclerotic plaques and modulates the phenotypic transition of vascular smooth muscle cells through KLF4 downregulation. Experimental & Molecular Medicine. 2023; 55: 426\u2013442.","DOI":"10.1038\/s12276-023-00937-x"},{"key":"ref119","doi-asserted-by":"publisher","unstructured":"Evans BR, Schulz J, Triantafyllidou V, Yerly A, Thakur M, Angliker N, et al. ChemR23 prevents phenotypic switching of vascular smooth muscle cells into macrophage-like foam cells in atherosclerosis. Cardiovascular Research. 2026; 122: 195\u2013213.","DOI":"10.1093\/cvr\/cvaf258"},{"key":"ref120","doi-asserted-by":"publisher","unstructured":"Li S, Chen K, Zhang Y, Yu Y, Zhang T, Jiang D, et al. TSPAN4 controls vascular smooth muscle cell phenotypic switching and intimal hyperplasia by targeting TPM1-regulated cytoskeletal organization. Clinical Science (London, England: 1979). 2025; 139: 1145\u20131161.","DOI":"10.1042\/CS20255833"},{"key":"ref121","doi-asserted-by":"publisher","unstructured":"Liu Y, Zeng L, Cai Q, Zeng Y, Zheng S, Gong X, et al. Cytoskeletal-related genes function as checkpoints for the maintenance of VSMC contractile phenotype and prevent pathological remodeling in arterial diseases. Journal of Advanced Research. 2026; 81: 689\u2013707.","DOI":"10.1016\/j.jare.2025.05.065"},{"key":"ref122","doi-asserted-by":"publisher","unstructured":"Zhu Y, Zhang JL, Yan XJ, Ji Y, Wang FF. Exploring a new mechanism between lactate and VSMC calcification: PARP1\/POLG\/UCP2 signaling pathway and imbalance of mitochondrial homeostasis. Cell Death & Disease. 2023; 14: 598.","DOI":"10.1038\/s41419-023-06113-3"},{"key":"ref123","doi-asserted-by":"publisher","unstructured":"Lin J, Wang X, Gu M, Chen Y, Xu J, Chau NV, et al. Geniposide ameliorates atherosclerosis by restoring lipophagy via suppressing PARP1\/PI3K\/AKT signaling pathway. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology. 2024; 129: 155617.","DOI":"10.1016\/j.phymed.2024.155617"},{"key":"ref124","doi-asserted-by":"publisher","unstructured":"Yang Y, Li X, Xiao S, Wei Q, Ren L, Yao Y, et al. PARylation of POLG Mediated by PARP1 Accelerates Ferroptosis-Induced Vascular Calcification via Activating Adora2a\/Rap1 Signaling. Arteriosclerosis, Thrombosis, and Vascular Biology. 2025; 45: 1175\u20131191.","DOI":"10.1161\/ATVBAHA.124.321682"},{"key":"ref125","doi-asserted-by":"publisher","unstructured":"Xu W, Wu Y, Mao R, Jia Y, Jiang H, Zhang F, et al. Poly(ADP-ribose) polymerase 1 orchestrates vascular smooth muscle cell homeostasis in arterial disease. Experimental & Molecular Medicine. 2025; 57: 1686\u20131699.","DOI":"10.1038\/s12276-025-01501-5"},{"key":"ref126","doi-asserted-by":"publisher","unstructured":"Wang SF, Yang LY, Zhao AQ, Wang ZY, Wang S, Gong M, et al. A Novel Hidden Protein p-414aa Encoded by circSETD2(14,15) Inhibits Vascular Remodeling. Circulation. 2025; 151: 1568\u20131582.","DOI":"10.1161\/CIRCULATIONAHA.124.070243"},{"key":"ref127","doi-asserted-by":"publisher","unstructured":"Xu S, Kamato D, Little PJ, Nakagawa S, Pelisek J, Jin ZG. Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics. Pharmacology & Therapeutics. 2019; 196: 15\u201343.","DOI":"10.1016\/j.pharmthera.2018.11.003"},{"key":"ref128","doi-asserted-by":"publisher","unstructured":"Libby P. The changing landscape of atherosclerosis. Nature. 2021; 592: 524\u2013533.","DOI":"10.1038\/s41586-021-03392-8"},{"key":"ref129","doi-asserted-by":"publisher","unstructured":"Rurik JG, Tomb\u00e1cz I, Yadegari A, M\u00e9ndez Fern\u00e1ndez PO, Shewale SV, Li L, et al. CAR T cells produced in vivo to treat cardiac injury. Science (New York, N.Y.). 2022; 375: 91\u201396.","DOI":"10.1126\/science.abm0594"},{"key":"ref130","doi-asserted-by":"publisher","unstructured":"Goebeler ME, Bargou RC. T cell-engaging therapies - BiTEs and beyond. Nature Reviews. Clinical Oncology. 2020; 17: 418\u2013434.","DOI":"10.1038\/s41571-020-0347-5"},{"key":"ref131","doi-asserted-by":"publisher","unstructured":"Aghajanian H, Kimura T, Rurik JG, Hancock AS, Leibowitz MS, Li L, et al. Targeting cardiac fibrosis with engineered T cells. 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Advanced Science (Weinheim, Baden-Wurttemberg, Germany). 2025; 12: e04990.","DOI":"10.1002\/advs.202504990"},{"key":"ref135","doi-asserted-by":"publisher","unstructured":"Maiseyeu A, Di L, Ravodina A, Barajas-Espinosa A, Sakamoto A, Chaplin A, et al. Plaque-targeted, proteolysis-resistant, activatable and MRI-visible nano-GLP-1 receptor agonist targets smooth muscle cell differentiation in atherosclerosis. Theranostics. 2022; 12: 2741\u20132757.","DOI":"10.7150\/thno.66456"},{"key":"ref136","doi-asserted-by":"publisher","unstructured":"Suzuki I, Ashraf A, Patel N, Huang Y, Lam B, Kim D, et al. Clinically relevant dosing of miR-145 micelles curbs atherosclerosis in vivo. Journal of Controlled Release: Official Journal of the Controlled Release Society. 2025; 384: 113930.","DOI":"10.1016\/j.jconrel.2025.113930"},{"key":"ref137","doi-asserted-by":"publisher","unstructured":"Chin DD, Poon C, Wang J, Joo J, Ong V, Jiang Z, et al. miR-145 micelles mitigate atherosclerosis by modulating vascular smooth muscle cell phenotype. Biomaterials. 2021; 273: 120810.","DOI":"10.1016\/j.biomaterials.2021.120810"},{"key":"ref138","doi-asserted-by":"publisher","unstructured":"Chin DD, Patel N, Lee W, Kanaya S, Cook J, Chung EJ. Long-term, in vivo therapeutic effects of a single dose of miR-145 micelles for atherosclerosis. Bioactive Materials. 2023; 27: 327\u2013336.","DOI":"10.1016\/j.bioactmat.2023.04.001"},{"key":"ref139","doi-asserted-by":"publisher","unstructured":"Li Z, Zhu H, Liu H, Liu D, Liu J, Jiang J, et al. Evolocumab loaded Bio-Liposomes for efficient atherosclerosis therapy. Journal of Nanobiotechnology. 2023; 21: 158.","DOI":"10.1186\/s12951-023-01904-4"},{"key":"ref140","doi-asserted-by":"publisher","unstructured":"Han JH, Heo JB, Lee HW, Park MH, Choi J, Yun EJ, et al. Novel carbazole attenuates vascular remodeling through STAT3\/CIAPIN1 signaling in vascular smooth muscle cells. Acta Pharmaceutica Sinica. B. 2025; 15: 1463\u20131479.","DOI":"10.1016\/j.apsb.2024.12.035"},{"key":"ref141","doi-asserted-by":"publisher","unstructured":"Feil S, Stowbur D, Sch\u00f6rg BF, Ehrlichmann W, Reischl G, Kneilling M, et al. Noninvasive Detection of Smooth Muscle Cell-Derived Hot Spots to Study Atherosclerosis by PET\/MRI in Mice. Circulation Research. 2023; 132: 747\u2013750.","DOI":"10.1161\/CIRCRESAHA.122.322296"},{"key":"ref142","doi-asserted-by":"publisher","unstructured":"Wu M, Ning J, Li J, Lai Z, Shi X, Xing H, et al. Feasibility of In Vivo Imaging of Fibroblast Activation Protein in Human Arterial Walls. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine. 2022; 63: 948\u2013951.","DOI":"10.2967\/jnumed.121.262863"},{"key":"ref143","doi-asserted-by":"publisher","unstructured":"Kosmala A, Serfling SE, Michalski K, Lindner T, Schirbel A, Higuchi T, et al. Molecular imaging of arterial fibroblast activation protein: association with calcified plaque burden and cardiovascular risk factors. European Journal of Nuclear Medicine and Molecular Imaging. 2023; 50: 3011\u20133021.","DOI":"10.1007\/s00259-023-06245-w"},{"key":"ref144","doi-asserted-by":"publisher","unstructured":"Criqui MH, Knox JB, Denenberg JO, Forbang NI, McClelland RL, Novotny TE, et al. Coronary Artery Calcium Volume and Density: Potential Interactions and Overall Predictive Value: The Multi-Ethnic Study of Atherosclerosis. JACC. Cardiovascular Imaging. 2017; 10: 845\u2013854.","DOI":"10.1016\/j.jcmg.2017.04.018"},{"key":"ref145","doi-asserted-by":"publisher","unstructured":"Wu Q, Pan W, Wu G, Wu F, Guo Y, Zhang X. CD40-targeting magnetic nanoparticles for MRI\/optical dual-modality molecular imaging of vulnerable atherosclerotic plaques. 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