Kurzfassung

In the present research proposal, we plan to study the potential of WS1442 to reverse eNOS uncoupling. For this purpose, the atherosclerosis‐prone, hypercholesterolemic ApoE‐KO mice on Western‐type diet will be treated orally with WS1442 for 14 days. Then, eNOS coupling status will be analyzed in the heart, the aorta, and the peri‐aortic adipose tissue. As BH4 deficiency (due to enhance oxidation or reduced biosynthesis) represents the major cause of eNOS uncoupling, redox enzymes (NADPH...In the present research proposal, we plan to study the potential of WS®1442 to reverse eNOS uncoupling. For this purpose, the atherosclerosis‐prone, hypercholesterolemic ApoE‐KO mice on Western‐type diet will be treated orally with WS®1442 for 14 days. Then, eNOS coupling status will be analyzed in the heart, the aorta, and the peri‐aortic adipose tissue. As BH4 deficiency (due to enhance oxidation or reduced biosynthesis) represents the major cause of eNOS uncoupling, redox enzymes (NADPH oxidases, xanthine oxidase, SOD1‐3, catalase, GPx1) and BH4‐synthesizing enzymes (GTPCH1 and DHFR) will be studied. In addition, eNOS expression, eNOS phosphorylation and eNOS S‐glutathionylation will also be studied to explore the underlying mechanisms.» weiterlesen» einklappen