DNA Methyltransferase 1-Dependent DNA Hypermethylation Constrains Arteriogenesis by Augmenting Shear Stress Set Point.

ABSTRACT:

Background

Arteriogenesis is initiated by increased shear stress and is thought to continue until shear stress is returned to its original "set point." However, the molecular mechanism(s) through which shear stress set point is established by endothelial cells (ECs) are largely unstudied. Here, we tested the hypothesis that DNA methyltransferase 1 (DNMT1)-dependent EC DNA methylation affects arteriogenic capacity via adjustments to shear stress set point.

Methods and results

In femoral artery ligation-operated C57BL/6 mice, collateral artery segments exposed to increased shear stress without a change in flow direction (ie, nonreversed flow) exhibited global DNA hypermethylation (increased 5-methylcytosine staining intensity) and constrained arteriogenesis (30% less diameter

SUBMITTER: Heuslein JL 

PROVIDER: S-EPMC5779061 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature