Abstract 2057: Serine Hydroxymethyltransferase 2 In Hepatocytes Regulates One-carbon Metabolism, Circulating VLDL And Atherosclerosis

• DOI: 10.1161/atvb.44.suppl_1.2057
• Publication Date: 2024-07-24T13:03:55Z
• Authors: Mary P McKinney; Alia Ghrayeb; Alexandra Finney; SUMIT K ANAND; Sumati Rohilla; Sandeep Das; Brenna Pearson-ga...; Lin Tan; Philip Lorenzi; Wayne W Orr; Arif Yurdagul; Inbal Mor; Eyal Gottlieb; Oren Rom
• Keywords: Serine hydroxymethyltransferase

While the role of lipids in atherosclerotic cardiovascular disease (ASCVD) is well studied, contribution amino acids becoming increasingly recognized. We and others reported that ratio glycine to serine reduced association with ASCVD severity. Primarily expressed liver, hydroxymethyltransferase 2 (SHMT2) thought be responsible for bulk biosynthesis from serine. recently reversed SHMT2 activity fatty livers drives depletion ( Ghrayeb et al. Cell Metab 2024 ). Nevertheless, whether regulation glycine/serine metabolism by hepatic affects atherosclerosis remains unknown. Utilizing novel hepatocyte-specific Shmt2 knockout mice HKO ) crossed apolipoprotein E-deficient Apoe -/- mice, metabolomics, transcriptomics, we studied hepatocyte atherosclerosis. found a significant increase glycine:serine plasma / compered flox fed Western diet. In decreased S-adenosylmethionine (SAM) increased adenosylhomocysteine (SAH) resulted SAM:SAH ratio. steatosis was unaltered, had lower phosphatidylcholine (PC) PC:phosphatidylethanolamine (PE) ratio, key regulators VLDL assembly secretion. Accordingly, FPLC demonstrated triglyceride cholesterol contents mice. Moreover, RNA-seq qPCR analyses revealed downregulation proinflammatory mediators Tnf, Ir1b, Ccr5 an upregulation acid β-oxidation Acadm , Acadl Finally, histological analysis aortic sinuses plaque size female These studies uncover as regulator one-carbon