Deficient eNOS phosphorylation is a mechanism for diabetic vascular dysfunction contributing to increased stroke size.

ABSTRACT:

Background and purpose

Phosphorylation of eNOS, an important post-translational modulator of its enzymatic activity, is reduced in diabetes mellitus. We hypothesized that modulation of eNOS phosphorylation could overcome diabetic vascular dysfunction and improves the outcome to stroke.

Methods

We used the db/db mouse model of type 2 diabetes mellitus. We mated db/db mice with eNOS knock-in mice that carry single amino acid mutations at the S1176 phosphorylation site; the phosphomimetic SD mutation (serine replaced by aspartate) shows increased eNOS enzymatic activity, whereas the unphosphorylatable SA mutation (serine replaced by alanine) shows decreased eNOS activity. We characterized the vascular anatomy, baseline physiological parameters, and vascular reactivity. We used

SUBMITTER: Li Q 

PROVIDER: S-EPMC3864831 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature