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- W4387620936 abstract "Background: The contractile phenotype of differentiated VSMCs is essential for vascular function. When exposed to Cholesterol (CHO), VSMCs dedifferentiate and acquire characteristics of foam cells, lipid-laden macrophage-like cells that comprise the Atherosclerotic plaques. CHO uptake by VSMCs is either removed by ABCA1-mediated efflux or is stored in lipid droplets as cholesterol esters (CEs). CEs are formed by the reaction of CHO with fatty acids catalyzed by SOAT1. Thus, we hypothesize that fatty acid biosynthesis controls the formation of VSMC-derived foam cells. Results: In VSMCs, CHO treatment upregulates the lipogenic enzymes FASN (3.6±1 vs. 9.0±0.9 AU p<0.01) and acetyl-CoA carboxylase (ACC) (2.8±0.5 vs. 10.2±2.3 AU p=0.02) and induces the phosphorylation of ATP Citrate Lyase (ACLY) (1.4±0 vs. 6.2±1 AU). Consistent with the literature, these changes are accompanied by increased expression of the macrophage-related markers CD68 and KLF4. Significantly, downregulation of FASN inhibits the CHO-induced CD68 (9.1±0.8 vs. 4.6±1,9 p=0.002) and KLF4 (p=0.02) expression upregulation. FASN-deficient VSMCs failed to accumulate lipids and transition to a foam cell phenotype after CHO treatment measured by Oil Red O staining. Interestingly, FASN-deficient VSMCs have decreased expression of SOAT1 (p=0.04) and increased expression of the CHO efflux transporter ABCA1 (p=0.04). Conclusion: Our study shows lipogenic enzymes are upregulated during the VSMC to foam cell transition triggered by CHO treatment. FASN expression is required for VSMC-derived foam cell formation. Our data suggest that FASN participates in the esterification of CHO and foam cell formation and may contribute to atherosclerotic plaque accumulation. Thus, FASN may represent a novel target for therapeutic intervention." @default.
- W4387620936 created "2023-10-14" @default.
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- W4387620936 date "2023-08-04" @default.
- W4387620936 modified "2023-10-15" @default.
- W4387620936 title "Abstract P3029: The Role Of Fatty Acid Synthase In The Modulation Of Vascular Smooth Muscle Cells Into A Foam Cell Phenotype" @default.
- W4387620936 doi "https://doi.org/10.1161/res.133.suppl_1.p3029" @default.
- W4387620936 hasPublicationYear "2023" @default.
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