eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2026-09-30 19 3 2690 2698 10.13005/bpj/3525 73466 article Maira Alsaeed 1 Gursev Dhaunsi 1 Department of Pediatrics, College of Medicine, Kuwait University, Jabriya, Kuwait High glucose and palmitic acid levels are believed to increase cellular oxidative stress and the risk of cardiovascular complications related to diabetes and obesity. We examined the effect of an Eicosapentaenoic acid (EPA), a cardioprotective agent, on Vascular endothelial growth factor (VEGF) function in rat aortic smooth muscles cells treated high glucose and palmitic acid. Primary cultures of smooth muscle cells were set up by enzymic digestion of the medial layer and maintained in DMEM F-12 medium. Confluent cell cultures were treated with palmitic acid (500 µM) and /or EPA (100 µM) with / without high glucose (25 mM). Mitogenic function of VEGF (100ng/ml) was measured by BrdU incorporation and NADPH oxidase (NOX) activity was assayed by chemiluminescence method. VEGF receptor1 expression was assessed by Western blotting. VEGF-induced BrdU incorporation was increased (p < 0.01) by high glucose and addition of palmitic acid further potentiated DNA synthesis. Both high glucose and palmitic acid increased (p < 0.01) the enzymatic activity of NOX and VEGF receptor levels. Diphenyliodonium, a NOX inhibitor, attenuated glucose or Palmitic acid -mediated increase in VEGF-mediated BrdU incorporation. Further, EPA (100 µM) also markedly reduced the incremental effect on NOX activity, VEGF receptor expression and VEGF mitogenic function.  These results suggest that NOX-mediated increase in VEGF mitogenic activity by high glucose and palmitic acid may be involved in diabetes and obesity related events, and EPA is a potential therapeutic agent. https://biomedpharmajournal.org/vol19no3/eicosapentaenoic-acid-attenuates-high-glucose-and-palmitic-acid-induced-vegf-function-via-nadph-oxidase-inhibition-in-vascular-smooth-muscle-cells/ Hyperglycemia NADPH oxidase Eicosapentaenoic acid Obesity Vascular smooth muscle cells VEGF