{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:59:50Z","timestamp":1785437990123,"version":"3.56.0"},"reference-count":100,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82274405"],"award-info":[{"award-number":["82274405"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82274405"],"award-info":[{"award-number":["82274405"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Joint Fund Cultivation Project of the Natural Science Foundation of Heilongjiang Province in 2025","award":["PL2025H240"],"award-info":[{"award-number":["PL2025H240"]}]},{"name":"Basic Research Support Program for Outstanding Young Teachers in Undergraduate Universities of Heilongjiang Province","award":["YQJH2024227"],"award-info":[{"award-number":["YQJH2024227"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Atherosclerosis (AS) is the primary underlying cause of cardiovascular and cerebrovascular diseases. The occurrence and development of AS are closely related to lipid deposition, chronic inflammation, phenotypic modulation of vascular smooth muscle cells (VSMCs), and extracellular matrix (ECM) remodeling. Numerous studies indicate that low-density lipoprotein receptor-associated protein 1 (LRP1), as a multifunctional receptor, contributes to vascular homeostasis in AS and vascular remodeling by regulating lipid handling, inflammatory responses, transforming growth factor beta (TGF\u03b2) signaling, and platelet-derived growth factor receptor beta (PDGFR\u03b2) trafficking. Rather than treating the LRP1-TGF\u03b2-PDGFR\u03b2 relationship as a fully established linear pathway, this review distinguishes demonstrated mechanisms from inferred cross-talk and proposes an integrated, cell- and stage-dependent regulatory model. This article systematically elaborates on the structure and function of LRP1; LRP1-mediated regulation of TGF\u03b2 and PDGFR\u03b2 in AS and vascular remodeling; the possible relationship among LRP1, TGF\u03b2, and PDGFR\u03b2; and cell-specific effects in VSMCs, macrophages, endothelial cells, and pericytes. Meanwhile, this article summarizes potential translational strategies such as lipid-lowering, anti-inflammatory therapy, PDGFR\u03b2 inhibitor repositioning, TGF\u03b2 pathway modulation, biomarker-based stratification, and LRP1-targeted delivery. A deeper understanding of the cell-specificity and stage-dependence of the LRP1-TGF\u03b2-PDGFR\u03b2 signaling network may help elucidate the progression mechanism of AS and provide new ideas for risk stratification and precise intervention.<\/jats:p>","DOI":"10.3390\/ijms27125421","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T03:27:21Z","timestamp":1781666841000},"page":"5421","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Research Progress on the Molecular Mechanism of LRP1 and TGF\u03b2-PDGFR\u03b2 Signaling Network in Atherosclerosis and Vascular Remodeling"],"prefix":"10.3390","volume":"27","author":[{"given":"Xuan","family":"Guo","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Xue","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingtong","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinbiao","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyue","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukun","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenying","family":"Niu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114177","DOI":"10.1016\/j.biopha.2022.114177","article-title":"Celastrol: The new dawn in the treatment of vascular remodeling diseases","volume":"158","author":"Tan","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1161\/CIRCRESAHA.124.325269","article-title":"LRP1 Repression by SNAIL Results in ECM Remodeling in Genetic Risk for Vascular Diseases","volume":"135","author":"Liu","year":"2024","journal-title":"Circ. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/s41586-021-03392-8","article-title":"The changing landscape of atherosclerosis","volume":"592","author":"Libby","year":"2021","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/j.cell.2022.04.004","article-title":"Atherosclerosis: Recent developments","volume":"185","author":"Lusis","year":"2022","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Luo, T., Zhang, Z., Xu, J., Liu, H., Cai, L., Huang, G., Wang, C., Chen, Y., Xia, L., and Ding, X. (2023). Atherosclerosis treatment with nanoagent: Potential targets, stimulus signals and drug delivery mechanisms. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1205751"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"111667","DOI":"10.1016\/j.biopha.2021.111667","article-title":"The molecular mechanism of LRP1 in physiological vascular homeostasis and signal transduction pathways","volume":"139","author":"He","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1111\/os.70035","article-title":"LRP1 Mediates Endocytosis Activity and Is a Potential Therapeutic Target in Osteoarthritis","volume":"17","author":"Wu","year":"2025","journal-title":"Orthop. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e185975","DOI":"10.1172\/jci.insight.185975","article-title":"LRP1 regulates asthmatic airway smooth muscle proliferation through FGF2\/ERK signaling","volume":"10","author":"Deng","year":"2025","journal-title":"JCI Insight"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"D1670","DOI":"10.1093\/nar\/gkae973","article-title":"Generic Diagramming Platform (GDP): A comprehensive database of high-quality biomedical graphics","volume":"53","author":"Jiang","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s11883-025-01364-1","article-title":"The Role of the PI3K\/Akt\/mTOR Pathway in Atherosclerosis: Mechanisms, Therapeutic Potential, and Emerging Targeted Treatments","volume":"27","author":"Zhang","year":"2025","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"107833","DOI":"10.1016\/j.phrs.2025.107833","article-title":"VSMCs in atherosclerosis: Implications on the role of inflammation and extracellular matrix remodelling","volume":"218","author":"Jarad","year":"2025","journal-title":"Pharmacol. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1007\/s00109-024-02439-3","article-title":"Mechanism of efferocytosis in atherosclerosis","volume":"102","author":"Shu","year":"2024","journal-title":"J. Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/s41569-024-01037-7","article-title":"Efferocytosis in atherosclerosis","volume":"21","author":"Adkar","year":"2024","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Guo, J., and Du, L. (2024). An update on ox-LDL-inducing vascular smooth muscle cell-derived foam cells in atherosclerosis. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1481505"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1097\/MOL.0000000000000776","article-title":"LDL receptor-related protein 1 and its interacting partners in tissue homeostasis","volume":"32","author":"Jaeschke","year":"2021","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"121412","DOI":"10.1016\/j.lfs.2023.121412","article-title":"Slug enables redox-sensitive trans-activation of LRP1 by COUP-TFII: Implication in antifibrotic intervention in the kidneys","volume":"316","author":"Wu","year":"2023","journal-title":"Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e163822","DOI":"10.1172\/jci.insight.163822","article-title":"LRP1 in vascular mural cells modulates cerebrovascular integrity and function in the presence of APOE4","volume":"8","author":"Oue","year":"2023","journal-title":"JCI Insight"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1161\/CIRCRESAHA.125.326297","article-title":"Lkb1 Downregulation Links PVAT Remodeling to Aortic Dilation or Aneurysm","volume":"137","author":"Cai","year":"2025","journal-title":"Circ. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"113171","DOI":"10.1016\/j.celrep.2023.113171","article-title":"Myeloid BAF60a deficiency alters metabolic homeostasis and exacerbates atherosclerosis","volume":"42","author":"Zhao","year":"2023","journal-title":"Cell Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.trsl.2024.05.009","article-title":"LncRNA MFRL regulates the phenotypic switch of vascular smooth muscle cells to attenuate arterial remodeling by encoding a novel micropeptide MFRLP","volume":"272","author":"Liu","year":"2024","journal-title":"Transl. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"G\u00e9m, J.B., Kov\u00e1cs, K.B., Szalai, L., Szakad\u00e1ti, G., Porkol\u00e1b, E., Szalai, B., Turu, G., T\u00f3th, A.D., Szekeres, M., and Hunyady, L. (2021). Characterization of Type 1 Angiotensin II Receptor Activation Induced Dual-Specificity MAPK Phosphatase Gene Expression Changes in Rat Vascular Smooth Muscle Cells. Cells, 10.","DOI":"10.3390\/cells10123538"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"122811","DOI":"10.1016\/j.lfs.2024.122811","article-title":"M1\/M2 macrophage-targeted nanotechnology and PROTAC for the treatment of atherosclerosis","volume":"352","author":"Ma","year":"2024","journal-title":"Life Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"101250","DOI":"10.1016\/j.molmet.2021.101250","article-title":"Myeloid cell-specific Irf5 deficiency stabilizes atherosclerotic plaques in Apoe\u2212\/\u2212 mice","volume":"53","author":"Leipner","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1161\/ATVBAHA.121.316854","article-title":"Macrophage LRP1 (Low-Density Lipoprotein Receptor-Related Protein 1) Is Required for the Effect of CD47 Blockade on Efferocytosis and Atherogenesis\u2014Brief Report","volume":"42","author":"Mueller","year":"2022","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Liu, S.-F., Veetil, N.N., Li, Q., Kucherenko, M.M., Knosalla, C., and Kuebler, W.M. (2022). Pulmonary hypertension: Linking inflammation and pulmonary arterial stiffening. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.959209"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1016\/j.bpj.2023.02.030","article-title":"Computational modeling of TGF-\u03b22:T\u03b2RI:T\u03b2RII receptor complex assembly as mediated by the TGF-\u03b2 coreceptor betaglycan","volume":"122","author":"Madamanchi","year":"2023","journal-title":"Biophys. J."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Danielpour, D. (2024). Advances and Challenges in Targeting TGF-\u03b2 Isoforms for Therapeutic Intervention of Cancer: A Mechanism-Based Perspective. Pharmaceuticals, 17.","DOI":"10.3390\/ph17040533"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/s41573-021-00198-1","article-title":"Targeting inflammation in atherosclerosis\u2014From experimental insights to the clinic","volume":"20","author":"Soehnlein","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Mendoza, F.A., Piera-Velazquez, S., and Jimenez, S.A. (2025). Role of Growth Factors in the Pathogenesis of Systemic-Sclerosis-Associated Fibrosis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26199596"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1161\/ATVBAHA.123.321067","article-title":"Loss of Smooth Muscle Tenascin-X Inhibits Vascular Remodeling Through Increased TGF-\u03b2 Signaling","volume":"44","author":"Liang","year":"2024","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"16323","DOI":"10.1038\/s41598-024-67006-9","article-title":"EVs-miR-17-5p attenuates the osteogenic differentiation of vascular smooth muscle cells potentially via inhibition of TGF-\u03b2 signaling under high glucose conditions","volume":"14","author":"Baba","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"C1721","DOI":"10.1152\/ajpcell.00587.2023","article-title":"NEAT1 regulates VSMC differentiation and calcification in as long noncoding RNA NEAT1 enhances phenotypic and osteogenic switching of vascular smooth muscle cells in atherosclerosis via scaffolding EZH2","volume":"326","author":"Yin","year":"2024","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e2408660","DOI":"10.1002\/advs.202408660","article-title":"Hepatic Steatosis Aggravates Vascular Calcification via Extracellular Vesicle-Mediated Osteochondrogenic Switch of Vascular Smooth Muscle Cells","volume":"12","author":"Zeng","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s12987-021-00260-5","article-title":"Brain endothelial LRP1 maintains blood\u2013brain barrier integrity","volume":"18","author":"Storck","year":"2021","journal-title":"Fluids Barriers CNS"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"107457","DOI":"10.1016\/j.vph.2024.107457","article-title":"The role of Epsins in atherosclerosis: From molecular mechanisms to therapeutic applications","volume":"158","author":"Dabravolski","year":"2025","journal-title":"Vasc. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e20202207","DOI":"10.1084\/jem.20202207","article-title":"Endothelial LRP1 protects against neurodegeneration by blocking cyclophilin A","volume":"218","author":"Nikolakopoulou","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Hou, Z., Deng, L., Fang, F., Zhao, T., Zhang, Y., Li, G., Miao, M.Z., Zhang, Y., Yu, H., and Liu, X. (2025). Endothelial cells under disturbed flow release extracellular vesicles to promote inflammatory polarization of macrophages and accelerate atherosclerosis. BMC Biol., 23.","DOI":"10.1186\/s12915-025-02125-x"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Chen, J., Su, Y., Pi, S., Hu, B., and Mao, L. (2021). The Dual Role of Low-Density Lipoprotein Receptor-Related Protein 1 in Atherosclerosis. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.682389"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/s41392-024-01840-1","article-title":"Macrophages in cardiovascular diseases: Molecular mechanisms and therapeutic targets","volume":"9","author":"Chen","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/s42255-020-00338-8","article-title":"Multiple cell types contribute to the atherosclerotic lesion fibrous cap by PDGFR\u03b2 and bioenergetic mechanisms","volume":"3","author":"Newman","year":"2021","journal-title":"Nat. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e19114","DOI":"10.7717\/peerj.19114","article-title":"CDCP1 knockdown suppresses PDGFR\u03b2\/AKT pathway-mediated vascular smooth muscle cell proliferation by inhibiting PDGFR\u03b2 endocytosis","volume":"13","author":"Ji","year":"2025","journal-title":"PeerJ"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7398","DOI":"10.1038\/s41467-024-51881-x","article-title":"PTPN14 aggravates neointimal hyperplasia via boosting PDGFR\u03b2 signaling in smooth muscle cells","volume":"15","author":"Ma","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"109702","DOI":"10.1016\/j.intimp.2023.109702","article-title":"Thymosin \u03b24 preserves vascular smooth muscle phenotype in atherosclerosis via regulation of low density lipoprotein related protein 1 (LRP1)","volume":"115","author":"Munshaw","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e127884","DOI":"10.1172\/JCI127884","article-title":"Thymosin \u03b24 protects against aortic aneurysm via endocytic regulation of growth factor signaling","volume":"131","author":"Munshaw","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1177\/0271678X221145092","article-title":"PDGFR\u03b2-positive cell-mediated post-stroke remodeling of fibronectin and laminin \u03b12 for tissue repair and functional recovery","volume":"43","author":"Shibahara","year":"2023","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"113698","DOI":"10.1016\/j.isci.2025.113698","article-title":"Mapping atherogenesis mechanisms in smooth muscle cells by targeting genes linked to coronary artery disease","volume":"28","author":"Markov","year":"2025","journal-title":"iScience"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"8255","DOI":"10.1038\/s41467-025-63202-x","article-title":"Integrated single-cell atlas of human atherosclerotic plaques","volume":"16","author":"Traeuble","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1016\/j.jacc.2024.02.053","article-title":"Personalized Intervention Based on Early Detection of Atherosclerosis: JACC State-of-the-Art Review","volume":"83","author":"Nielsen","year":"2024","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/s41440-025-02540-1","article-title":"Recent advances and emerging perspectives in vascular and cardiovascular research: A 2025 update","volume":"49","author":"Kishimoto","year":"2026","journal-title":"Hypertens. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"eadx1736","DOI":"10.1126\/science.adx1736","article-title":"Targeting modulated vascular smooth muscle cells in atherosclerosis via FAP-directed immunotherapy","volume":"392","author":"Amrute","year":"2026","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e13742","DOI":"10.1111\/cpr.13742","article-title":"CircSMAD3 represses VSMC phenotype switching and neointima formation via promoting hnRNPA1 ubiquitination degradation","volume":"58","author":"Mei","year":"2025","journal-title":"Cell Prolif."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"357","DOI":"10.3892\/etm.2024.12646","article-title":"GATA2-miR-374a axis promotes vascular smooth muscle cells proliferation, migration via targeting circTADA2A\/RORA axis","volume":"28","author":"Tu","year":"2024","journal-title":"Exp. Ther. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"118582","DOI":"10.1016\/j.atherosclerosis.2024.118582","article-title":"Gene inactivation of lysyl oxidase in smooth muscle cells reduces atherosclerosis burden and plaque calcification in hyperlipidemic mice","volume":"397","author":"Kumar","year":"2024","journal-title":"Atherosclerosis"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1093\/cvr\/cvae035","article-title":"Smooth muscle cell-specific matrix metalloproteinase 3 deletion reduces osteogenic transformation and medial artery calcification","volume":"120","author":"Xie","year":"2024","journal-title":"Cardiovasc. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.7150\/thno.87201","article-title":"Re-analysis of single-cell transcriptomics reveals a critical role of macrophage-like smooth muscle cells in advanced atherosclerotic plaque","volume":"14","author":"Gong","year":"2024","journal-title":"Theranostics"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Luo, L., Fu, C., Bell, C.F., Wang, Y., and Leeper, N.J. (2023). Role of vascular smooth muscle cell clonality in atherosclerosis. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1273596"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e37727","DOI":"10.1016\/j.heliyon.2024.e37727","article-title":"Vascular smooth muscle cell phenotypic switching in atherosclerosis","volume":"10","author":"Yu","year":"2024","journal-title":"Heliyon"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41420-025-02932-9","article-title":"Vascular smooth muscle cell metabolic reprogramming and phenotypic remodeling in atherosclerosis","volume":"12","author":"Fu","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e031121","DOI":"10.1161\/JAHA.123.031121","article-title":"Phenotypic Switching of Vascular Smooth Muscle Cells in Atherosclerosis","volume":"12","author":"Chen","year":"2023","journal-title":"J. Am. Heart Assoc."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"28240","DOI":"10.31083\/RCM28240","article-title":"Vascular Smooth Muscle Cells: A Therapeutic Target in Atherosclerosis","volume":"26","author":"Zhao","year":"2025","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1093\/cvr\/cvab046","article-title":"Vascular smooth muscle cells in atherosclerosis: Time for a re-assessment","volume":"117","author":"Grootaert","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1186\/s12964-022-00993-2","article-title":"How vascular smooth muscle cell phenotype switching contributes to vascular disease","volume":"20","author":"Cao","year":"2022","journal-title":"Cell Commun. Signal."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"106","DOI":"10.12997\/jla.2023.12.2.106","article-title":"Roles of Vascular Smooth Muscle Cells in Atherosclerotic Calcification","volume":"12","author":"Woo","year":"2023","journal-title":"J. Lipid Atheroscler."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"11282","DOI":"10.1038\/s41467-025-67679-4","article-title":"Single cell spatial transcriptomics integration deciphers the morphological heterogeneity of atherosclerotic carotid arteries","volume":"16","author":"Pauli","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Alonso-Herranz, L., Albarr\u00e1n-Ju\u00e1rez, J., and Bentzon, J.F. (2023). Mechanisms of fibrous cap formation in atherosclerosis. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1254114"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1161\/ATVBAHA.123.320274","article-title":"Secreted Protein Profiling of Human Aortic Smooth Muscle Cells Identifies Vascular Disease Associations","volume":"44","author":"Aherrahrou","year":"2024","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1161\/CIRCRESAHA.122.321538","article-title":"TXNIP Suppresses the Osteochondrogenic Switch of Vascular Smooth Muscle Cells in Atherosclerosis","volume":"132","author":"Woo","year":"2023","journal-title":"Circ. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"107256","DOI":"10.1016\/j.jbc.2024.107256","article-title":"Receptor-activated transcription factors and beyond: Multiple modes of Smad2\/3-dependent transmission of TGF-\u03b2 signaling","volume":"300","author":"Miyazawa","year":"2024","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Huang, Y., Ma, W., Guo, C., and Su, X. (2025). Mechanism of action and potential therapeutic targets of TGF-\u03b2-related signaling pathway and its downstream miRNA expression in pulmonary arterial hypertension. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1596767"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e164751","DOI":"10.1172\/jci.insight.164751","article-title":"LRP1 protects against excessive superior mesenteric artery remodeling by modulating angiotensin II\u2013mediated signaling","volume":"8","author":"Zhang","year":"2023","journal-title":"JCI Insight"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s11684-024-1056-8","article-title":"Targeting deubiquitinase OTUB1 protects vascular smooth muscle cells in atherosclerosis by modulating PDGFR\u03b2","volume":"18","author":"Xu","year":"2024","journal-title":"Front. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s00395-023-01023-z","article-title":"Macrophage profiling in atherosclerosis: Understanding the unstable plaque","volume":"119","author":"Gianopoulos","year":"2024","journal-title":"Basic Res. Cardiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/s41392-024-01764-w","article-title":"TGF-\u03b2 signaling in health, disease and therapeutics","volume":"9","author":"Deng","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/s41577-021-00584-1","article-title":"How the immune system shapes atherosclerosis: Roles of innate and adaptive immunity","volume":"22","author":"Roy","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e70008","DOI":"10.1002\/cph4.70008","article-title":"Redefining Macrophage Heterogeneity in Atherosclerosis: A Focus on Possible Therapeutic Implications","volume":"15","author":"Kanuri","year":"2025","journal-title":"Compr. Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Gong, S., Li, Y., Yan, K., Shi, Z., Leng, J., Bao, Y., and Ning, K. (2025). The Crosstalk Between Endothelial Cells, Smooth Muscle Cells, and Macrophages in Atherosclerosis. Int. J. Mol. Sci., 26.","DOI":"10.20944\/preprints202501.0324.v1"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e651","DOI":"10.1002\/mco2.651","article-title":"Endothelial dysfunction: Molecular mechanisms and clinical implications","volume":"5","author":"Wang","year":"2024","journal-title":"MedComm"},{"key":"ref_78","first-page":"250","article-title":"ROS-Induced Endothelial Dysfunction in the Pathogenesis of Atherosclerosis","volume":"16","author":"Yan","year":"2024","journal-title":"Aging Dis."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Zhang, L., Wu, X., and Hong, L. (2024). Endothelial Reprogramming in Atherosclerosis. Bioengineering, 11.","DOI":"10.3390\/bioengineering11040325"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s44161-024-00582-1","article-title":"Encompassing view of spatial and single-cell RNA sequencing renews the role of the microvasculature in human atherosclerosis","volume":"4","author":"Bleckwehl","year":"2025","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/s44161-025-00639-9","article-title":"Single-cell spatial transcriptomics of tertiary lymphoid organ-like structures in human atherosclerotic plaques","volume":"4","author":"Lai","year":"2025","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1038\/s43587-025-00889-z","article-title":"Single-cell and spatial transcriptomics map senescent vascular cells in arterial remodeling during atherosclerosis in mice","volume":"5","author":"Tsitsipatis","year":"2025","journal-title":"Nat. Aging"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1042\/CS20220797","article-title":"Vascular remodelling in cardiovascular diseases: Hypertension, oxidation, and inflammation","volume":"138","author":"Mikolajczyk","year":"2024","journal-title":"Clin. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3415","DOI":"10.1093\/eurheartj\/ehae177","article-title":"2024 ESC Guidelines for the management of chronic coronary syndromes","volume":"45","author":"Vrints","year":"2024","journal-title":"Eur. Heart J."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1056\/NEJMoa2215024","article-title":"Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients","volume":"388","author":"Nissen","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3925","DOI":"10.1093\/eurheartj\/ehac361","article-title":"Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: A European Atherosclerosis Society consensus statement","volume":"43","author":"Kronenberg","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1161\/CIRCRESAHA.122.322360","article-title":"LncRNA PSMB8-AS1 Instigates Vascular Inflammation to Aggravate Atherosclerosis","volume":"134","author":"Li","year":"2024","journal-title":"Circ. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1093\/eurheartj\/ehaf174","article-title":"Long-term trials of colchicine for secondary prevention of vascular events: A meta-analysis","volume":"46","author":"Samuel","year":"2025","journal-title":"Eur. Heart J."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1161\/CIRCULATIONAHA.124.071344","article-title":"Colchicine and Atherothrombosis: Another Piece of the Puzzle","volume":"150","author":"Weber","year":"2024","journal-title":"Circulation"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"102835","DOI":"10.1016\/j.eclinm.2024.102835","article-title":"Colchicine for secondary prevention of ischaemic stroke and atherosclerotic events: A meta-analysis of randomised trials","volume":"76","author":"Fiolet","year":"2024","journal-title":"eClinicalMedicine"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e24284","DOI":"10.1002\/clc.24284","article-title":"The ABCs of the 2023 AHA\/ACC\/ACCP\/ASPC\/NLA\/PCNA guideline for the management of patients with chronic coronary disease","volume":"47","author":"Khorsandi","year":"2024","journal-title":"Clin. Cardiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"107570","DOI":"10.1016\/j.vph.2025.107570","article-title":"Smooth muscle cell phenotypic modulation during atherosclerosis","volume":"162","author":"Frausto","year":"2026","journal-title":"Vasc. Pharmacol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"123568","DOI":"10.1016\/j.lfs.2025.123568","article-title":"Edaravone targets PDGFR\u03b2 to attenuate VSMC phenotypic transition","volume":"370","author":"Tang","year":"2025","journal-title":"Life Sci."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Liuiz\u0117, A., and Mongirdien\u0117, A. (2024). TGF-\u03b2 Isoforms and GDF-15 in the Development and Progression of Atherosclerosis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042104"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Vistnes, M. (2024). Hitting the Target! Challenges and Opportunities for TGF-\u03b2 Inhibition for the Treatment of Cardiac fibrosis. Pharmaceuticals, 17.","DOI":"10.3390\/ph17030267"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1002\/ptr.8483","article-title":"New Roles of Artemisinins in Atherosclerosis Progression","volume":"39","author":"Majidiani","year":"2025","journal-title":"Phytother. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3445","DOI":"10.2147\/IJN.S508757","article-title":"How Advanced Is Nanomedicine for Atherosclerosis?","volume":"20","author":"Gu","year":"2025","journal-title":"Int. J. Nanomed."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Rong, Z., He, X., Fan, T., and Zhang, H. (2024). Nano Delivery System for Atherosclerosis. J. Funct. Biomater., 16.","DOI":"10.3390\/jfb16010002"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Karakasis, P., Theofilis, P., Vlachakis, P.K., Grigoriou, K., Patoulias, D., Antoniadis, A.P., and Fragakis, N. (2025). Reprogramming Atherosclerosis: Precision Drug Delivery, Nanomedicine, and Immune-Targeted Therapies for Cardiovascular Risk Reduction. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17081028"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1186\/s13195-025-01840-5","article-title":"Endothelial delivery of simvastatin by LRP1-targeted nanoparticles ameliorates pathogenesis of alzheimer\u2019s disease in a mouse model","volume":"17","author":"Pan","year":"2025","journal-title":"Alzheimer\u2019s Res. Ther."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5421\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T04:54:53Z","timestamp":1781844893000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5421"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,16]]},"references-count":100,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27125421"],"URL":"https:\/\/doi.org\/10.3390\/ijms27125421","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,16]]}}}