Divergent effects of genetic and pharmacological inhibition of Nox2 NADPH oxidase on insulin resistance related vascular damage.

Divergent effects of genetic and pharmacological inhibition of Nox2 NADPH oxidase on insulin resistance related vascular damage. Am J Physiol Cell Physiol. 2020 May 13;: Authors: Maqbool A, Watt N, Haywood N, Viswambharan H, Skromna A, Makava N, Visnagri A, Shawer HM, Bridge K, Muminov SK, Griffin K, Beech DJ, Wheatcroft SB, Porter KE, Simmons KJ, Sukumar P, Shah AM, Cubbon RM, Kearney MT, Yuldasheva NY Abstract Insulin resistance leads to excessive endothelial cell (EC) superoxide generation and accelerated atherosclerosis. The principal source of superoxide from the insulin-resistant endothelium is the Nox2 isoform of NADPH oxidase. Here we examine the therapeutic potential of Nox2 inhibition on: superoxide generation in saphenous vein EC (SVEC) from patients with advanced atherosclerosis and type 2 diabetes; and on vascular function, vascular damage and lipid deposition in Apolipoprotein E deficient (ApoE-/-) mice with EC specific insulin resistance (ESMIRO). To examine the effect of genetic inhibition of Nox2, ESMIRO mice deficient in ApoE-/- and Nox2 (ESMIRO/ApoE-/-/Nox2-/y) were generated and compared to ESMIRO/ApoE-/-/Nox2+/y littermates. To examine the effect of pharmacological inhibition of Nox2 we administered gp91dstat or scrambled peptide to ESMIRO/ApoE-/- mice. SVEC from diabetic patients had increased expression of Nox2 protein with concomitant increase in superoxide generation which could be reduced by the Nox2 inhibit...
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Tags: Am J Physiol Cell Physiol Source Type: research