Collateral Flow Evokes Distinct Endothelial Gene Expression

Biomechanical forces influence vascular function, but the molecular mechanisms regulating many of these mechano-activated cellular events remain largely uncharacterized. In particular, the vascular endothelium can sense alterations in hemodynamic shear stress which, in the context of adaptive remodeling or arteriogenesis, has been shown to lead to the generation of endothelial-derived signals critical for controlling blood vessel structure and function. Here, we sought to define the arteriogenic responses evoked in endothelial cells exposed to flow using transciptional profiling. Analysis of these transcriptional programs identified several genes previously shown to be important for endothelial-smooth muscle interactions and vascular remodeling, including the transcription factor kruppel-like factor 2 (KLF2). A lumped parameter model of the human coronary collateral circulation was used to simulate previously uncharacterized normal (NCC) and adaptive remodeling (ACC) coronary collateral shear stress waveforms. These waveforms were then applied to cultured human endothelial cells (EC) and the resulting differences in EC gene expression were assessed by genome-wide transcriptional profiling to identify genes distinctly regulated by collateral flow.