Preprint Highlight: PGC1α regulates the endothelial response to fluid shear stress via telomerase reverse transcriptase control of heme oxygenase-1.

Abstract

Endothelial cell alignment in response to fluid flow is critical for normal vascular function; however, the regulatory pathways that underlie this planar polarized cell behavior remain elusive. Applying both cell culture and in vivo mouse model approaches, the authors reveal a novel peroxisome proliferator gamma coactivator‐1α (PGC‐1α)‐driven signaling pathway that is required for endothelial alignment in response to laminar fluid shear stress. This work proposes a noncanonical function of telomerase reverse transcriptase (TERT) in modulating mitochondrial dynamics in endothelial cells, unique from its established role in telomere maintenance. This study is of broad interest, as this novel molecular pathway shown to regulate endothelial homeostasis, polarity, stress response, and quiescence may also impact these properties in diverse tissues.