Glucose‐6‐phosphate dehydrogenase is involved in regulation of arterial smooth muscle phenotype in metabolic syndrome (1076.5)

Rationale: Coronary artery undergoes remodeling in metabolic syndrome that increases the risk of developing cardiovascular diseases. However, the effects of metabolic syndrome in the remodeling of the coronary artery are not clearly understood. Recently we have shown that Glucose‐6‐Phosphate Dehydrogenase (G6PD) activity is involved in regulation of vascular smooth muscle phenotype. Therefore, we hypothesize that G6PD activity is involved in regulation of arterial smooth muscle phenotype in metabolic syndrome. Methods: To test this hypothesis we assayed G6PD activity in coronary arteries of pig model of metabolic syndrome (obese and lean) and in left internal mammary/radial arteries of human with metabolic syndrome (obese‐diabetic and obese‐non‐diabetic). We also assayed the markers of smooth muscle phenotype in these arteries. Results: G6PD activity was increased (P<0.05; N=3) in arteries of obese‐diabetic (0.44±0.08 nmol/min/mg protein) as compared to obese‐non‐diabetic (0.13±0.03 nmol/min/mg protein) patients. Similarly, G6PD activity was also increased (P<0.05; N=10‐12) in the arteries of obese (2.9±0.8 nmol/min/mg protein) as compared to lean (1.2±0.5 nmol/min/mg protein) pigs. Interestingly, we also found that the myosin heavy chain ‐ a gold standard marker of smooth muscle phenotype was downregulated in obese‐diabetic human and obese pig arteries as compared to arteries of obese‐non‐diabetic humans and lean pigs. Similarly, myocardin levels were also decreased. Conclusion: It appears that maladaptation of glucose metabolism and increased G6PD activity is involved in the regulation of arterial smooth muscle phenotype in metabolic syndrome.