{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:50:00Z","timestamp":1790779800222,"version":"4.1.0"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To delineate temporal and spatial dynamics of vascular smooth muscle cell (SMC) transcriptomic changes during aortic aneurysm development in Marfan syndrome (MFS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results:<\/jats:title>\n                    <jats:p>\n                      We performed single-cell RNA sequencing to study aortic root\/ascending aneurysm tissue from\n                      <jats:italic>Fbn1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>C1041G\/<\/jats:italic>\n                        +\n                      <\/jats:sup>\n                      (MFS) mice and healthy controls, identifying all aortic cell types. A distinct cluster of transcriptomically modulated SMCs (modSMCs) was identified in adult\n                      <jats:italic>Fbn1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>C1041G\/<\/jats:italic>\n                        +\n                      <\/jats:sup>\n                      mouse aortic aneurysm tissue only. Comparison with atherosclerotic aortic data (ApoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice) revealed similar patterns of SMC modulation but identified an MFS-specific gene signature, including plasminogen activator inhibitor-1 (\n                      <jats:italic>Serpine1<\/jats:italic>\n                      ) and Kruppel-like factor 4 (\n                      <jats:italic>Klf4<\/jats:italic>\n                      ). We identified 481 differentially expressed genes between modSMC and SMC subsets; functional annotation highlighted extracellular matrix modulation, collagen synthesis, adhesion, and proliferation. Pseudotime trajectory analysis of\n                      <jats:italic>Fbn1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>C1041G\/<\/jats:italic>\n                        +\n                      <\/jats:sup>\n                      SMC\/modSMC transcriptomes identified genes activated differentially throughout the course of phenotype modulation. While modSMCs were not present in young\n                      <jats:italic>Fbn1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>C1041G\/<\/jats:italic>\n                        +\n                      <\/jats:sup>\n                      mouse aortas despite small aortic aneurysm, multiple early modSMCs marker genes were enriched, suggesting activation of phenotype modulation. modSMCs were not found in nondilated adult\n                      <jats:italic>Fbn1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>C1041G\/<\/jats:italic>\n                        +\n                      <\/jats:sup>\n                      descending thoracic aortas. Single-cell RNA sequencing from human MFS aortic root aneurysm tissue confirmed analogous SMC modulation in clinical disease. Enhanced expression of TGF-\u03b2 (transforming growth factor beta)-responsive genes correlated with SMC modulation in mouse and human data sets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      Dynamic SMC phenotype modulation promotes extracellular matrix substrate modulation and aortic aneurysm progression in MFS. We characterize the disease-specific signature of modSMCs and provide temporal, transcriptomic context to the current understanding of the role TGF-\u03b2 plays in MFS aortopathy. Collectively, single-cell RNA sequencing implicates TGF-\u03b2 signaling and\n                      <jats:italic>Klf4<\/jats:italic>\n                      overexpression as potential upstream drivers of SMC modulation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.120.314670","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T05:01:01Z","timestamp":1595480461000},"page":"2195-2211","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":204,"title":["Single-Cell Transcriptomic Profiling of Vascular Smooth Muscle Cell Phenotype Modulation in Marfan Syndrome Aortic Aneurysm"],"prefix":"10.1161","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5291-5980","authenticated-orcid":true,"given":"Albert J.","family":"Pedroza","sequence":"first","affiliation":[{"name":"From the Department of Cardiothoracic Surgery (A.J.P., Y.T., R.S., S.C., K.N., N.Y., 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