G. S. De Silva1, M. S. Darwech1, K. S. Desai1, N. S. Harroun1, C. F. Semenkovich3, M. A. Zayed1,2 1Washington University In St. Louis,Division Of Vascular Surgery,Saint Louis, MO, USA 2Veterans Affairs St. Louis Health Care System,Division Of Vascular Surgery,Saint Louis, MO, USA 3Washington University In St. Louis,Division Of Endocrinology, Lipid, And Metabolism,Saint Louis, MO, USA
Introduction:
Ischemic stroke is the third most common cause of death in the United States, and diabetes (DM) is one of the strongest risk factors. In the setting of DM, de novo tissue lipogenesis is significantly altered, leading to differential expression of lipid species in various tissue beds. Central to this process is Fatty Acid Synthase (FAS), which regulates synthesis of long chain saturated fatty acids in various tissues. We recently observed higher levels of circulating serum FAS (sFAS) in patients with advanced vascular disease. We therefore hypothesized that sFAS expression and activity is altered between DM and non-DM patients
Methods:
For this study, we enrolled DM, non-DM, and control patients (no arterial occlusive disease) in an IRB-approved vascular biobank and database between October 2014 and February 2016. In consenting patients, fasting serum samples were collected and evaluated for sFAS content and activity using ELISA-based assays. Differences in sFAS content and activity across patient cohorts were summarized as mean ± SEM, and significance was determined using Kruskal-Wallis analysis, Mann-Whitney U test, and Spearman correlation analysis. All p-values 0.05 were considered to be significant
Results:
26 patients (13 DM, 13 Non-DM) undergoing carotid endarterectomy (CEA), as well as 13 control patients were prospectively enrolled and retrospectively reviewed. There were no significant differences between demographics of enrolled patients except the use of metformin in the DM cohort. sFAS activity was significantly higher in DM compared to non-DM patients (7.1 ± 0.85 vs 4.5 ± 0.74 pmoles of NADPH consumed/mg of protein; p=0.05). Both DM and non-DM patients had higher sFAS activity compared to control patients (2.7 ± 0.72; p =0.01). Although we did not observe a difference between FAS content between DM and non-DM patients (6.0 ± 1.4 vs 6.2 ± 1.2 ng/mL, p=0.99), patients with carotid artery stenosis had higher sFAS levels relative to control patients (6.1 ± 0.93 vs 1.5 ± 0.23 ng/mL; p<0.001)
Conclusion:
Our study confirms that sFAS circulates in the serum of DM and non-DM patients with high-grade carotid artery occlusive disease. sFAS activity appears to be higher in the serum of diabetic patients. These findings suggest that sFAS and its downstream effectors may serve as important biomarkers for disease progression in patients with DM and arterial occlusive disease.
