biostudies-literatureUnknownTan JMENIDDK NIH HHSNHLBI NIH HHSNIAMS NIH HHSVascular smooth muscle cells (SMCs) normally exist in a contractile state but can undergo fate switching to produce various cell phenotypes in response to pathologic stimuli^1-3. In atherosclerosis, these phenotypically modulated SMCs regulate plaque composition and influence the risk of major adverse cardiovascular events^4,5. We found that PRDM16, a transcription factor that is genetically associated with cardiovascular disease, is highly expressed in arterial SMCs and downregulated during SMC fate switching in human and mouse atherosclerosis. Loss of <i>Prdm16</i> in SMCs of mice activates a synthetic modulation program under homeostatic conditions. Single cell analyses show that loss of <i>Prdm16</i> drives a synthetic program in all SMC populations. Upon exposure tbioRxiv : the preprint server for biology2025.02.19.639186https://www.ebi.ac.uk/biostudies/studies/S-EPMC11870537biostudies-literaturePRDM16 controls smooth muscle cell fate in atherosclerosis.PMC11870537R01 HL169766R01 HL148239R21 AR078650R01 HL164577R01 DK120982R01 DK123356R01 HL166916R01 HL150359Miller CLLutgens EBarbara EWeller AHXue CReilly MPCalhoun RPTan JMESeale PAuguste GLim HWWinter HDrareni KFong SCheng LMaegdefessel LfalsePRDM16 controls smooth muscle cell fate in atherosclerosis.Vascular smooth muscle cells (SMCs) normally exist in a contractile state but can undergo fate switching to produce various cell phenotypes in response to pathologic stimuli^1-3. In atherosclerosis, these phenotypically modulated SMCs regulate plaque composition and influence the risk of major adverse cardiovascular events^4,5. We found that PRDM16, a transcription factor that is genetically associated with cardiovascular disease, is highly expressed in arterial SMCs and downregulated during SMC fate switching in human and mouse atherosclerosis. Loss of <i>Prdm16</i> in SMCs of mice activates a synthetic modulation program under homeostatic conditions. Single cell analyses show that loss of <i>Prdm16</i> drives a synthetic program in all SMC populations. Upon exposure t2025-01-01T00:00:00Z2025 Feb2026-04-18T03:18:22.13Z2025-04-04T00:29:43.647ZS-EPMC118705374002772910.1101/2025.02.19.639186