MEF2B-Nox1 signaling is critical for stretch-induced phenotypic modulation of vascular smooth muscle cells.

ABSTRACT:

Objective

Blood vessel hemodynamics have profound influences on function and structure of vascular cells. One of the main mechanical forces influencing vascular smooth muscle cells (VSMC) is cyclic stretch (CS). Increased CS stimulates reactive oxygen species (ROS) production in VSMC, leading to their dedifferentiation, yet the mechanisms involved are poorly understood. This study was designed to test the hypothesis that pathological CS stimulates NADPH oxidase isoform 1 (Nox1)-derived ROS via MEF2B, leading to VSMC dysfunction via a switch from a contractile to a synthetic phenotype.

Approach and results

Using a newly developed isoform-specific Nox1 inhibitor and gene silencing technology, we demonstrate that a novel pathway, including MEF2B-Nox1-ROS, is upregulated under p

SUBMITTER: Rodriguez AI 

PROVIDER: S-EPMC4409426 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature