Human prostaglandin transporter gene (hPGT) is regulated by fluid mechanical stimuli in cultured endothelial cells and expressed in vascular endothelium in vivo

Background-biomechanical forces generated by blood flow within the cardiova scular system have been proposed as important modulators of regional endoth elial phenotype and function. This process is thought to involve the regula tion of vascular gene expression by physiological fluid mechanical stimuli such as fluid sheer stresses. Methods and Results-We demonstrate sustained upregulation of a recently ide ntified gene encoding a human prostaglandin transporter (hPGT) in cultured human vascular endothelium exposed to a physiological fluid mechanical stim ulus in vitro. This biomechanical induction is selective in that steady lam inar shear stress is sufficient to upregulate the hPGT gene at the level of transcriptional activation, whereas a comparable level of turbulent sheer stress (a nonphysiological stimulus) is not. Various biochemical stimuli, s uch as bacterial endotoxin and the inflammatory cytokines recombinant human interleukin 1 beta cytokines (rhIL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), did not significantly induce hPGT. Using a specific antiserum to hPGT, we demonstrate endothelial expression within the arterial vascula ture and the microcirculation of highly vascularized tissues such as the he art. Conclusions-Our results identify hPGT as an inducible gene in vascular endo thelium and suggest that biomechanical stimuli generated by blood flow in v ivo may be important determinants of hPGT expression. Furthermore, this dem onstration of regulated endothelial expression of hPGT implicates this mole cule in the regional metabolism of prostanoids within the cardiovascular sy stem.