The effect of simvastatin treatment on endothelial cell response to shear stress and tumor necrosis factor alpha stimulation

• DOI: 10.1186/s12938-015-0057-x
• Publication Date: 2015-06-19T13:55:23Z
• Authors: Melissa Dick; Katherine MacDonald; Jean-Claude Tardif; Richard L Leask
• Keywords: Mechanotransduction

Statin drugs are one of the most commonly prescribed pharmaceuticals by physicians. By blocking rate-limiting step in cholesterol biosynthesis pathway, statins inhibit synthesis, which benefits patient health. However, since many other important cellular processes regulated within this they may also be influenced statin therapy. These pleiotropic effects have not been fully investigated, but believed to positively influence endothelial cells (ECs), line vasculature a confluent monolayer. Few studies considered effect blood flow on ECs and how augment EC response statins.In study, treatment is investigated for stimulated with tumor necrosis factor alpha (TNF-α), an inflammatory cytokine that promotes atheroprone endothelium. Additionally, exposed physiologically relevant wall shear stress (WSS) 12.5 dynes/cm(2) using three-dimensional tissue culture model provide realistic hemodynamic environment. analyzed morphology light microscopy as well cytoskeletal structure alignment confocal microscopy. Statistical analysis performed results both one-way variance Bonferroni post-tests two-tailed t test.We shown caused adapt rounded, morphology, significantly higher shape index. Oppositely, TNF-α stimulation elongate atheroprotective lower WSS were unable reverse any statin-induced cell rounding or F-actin disruption.Further work therefore needed determine why cause genotype, causes genotype. Despite morphological changes due stimulation, still respond WSS. Understanding will allow more targeted treatments hypercholestemia potentially diseases.