Articles by Paul Jonak in JoVE
Other articles by Paul Jonak on PubMed
Differential Response of Endothelial Cells to Simvastatin when Conditioned with Steady, Non-reversing Pulsatile or Oscillating Shear Stress Annals of Biomedical Engineering. Jan, 2011 | Pubmed ID: 20737288 Few studies have investigated whether fluid mechanics can impair or enhance endothelial cell response to pharmacological agents such as statin drugs. We evaluated and compared Kruppel-like factor 2 (KLF2), endothelial nitric oxide synthase (eNOS), and thrombomodulin (TM) expression in human abdominal aortic endothelial cells (HAAEC) treated with increasing simvastatin concentrations (0.1, 1 or 10Â Î¼M) under static culture and shear stress (steady, non-reversing pulsatile, and oscillating). Simvastatin, steady flow, and non-reversing pulsatile flow each separately upregulated KLF2, eNOS, and TM mRNA. At lower simvastatin concentrations (0.1 and 1Â Î¼M), the combination of statin and unidirectional steady or pulsatile flow produced an overall additive increase in mRNA levels. At higher simvastatin concentration (10Â Î¼M), a synergistic increase in eNOS and TM mRNA expression was observed. In contrast, oscillating flow impaired KLF2 and TM, but not eNOS expression by simvastatin at 1Â Î¼M. A higher simvastatin concentration of 10Â Î¼M overcame the inhibitory effect of oscillating flow. Our findings suggest that oscillating shear stress renders the endothelial cells less responsive to simvastatin than cells exposed to unidirectional steady or pulsatile flow. Consequently, the pleiotropic effects of statins in vivo may be less effective in endothelial cells exposed to atheroprone hemodynamics.
Statin Therapy Influences Endothelial Cell Morphology and F-actin Cytoskeleton Structure when Exposed to Static and Laminar Shear Stress Conditions Life Sciences. May, 2013 | Pubmed ID: 23517776 To determine how statin drugs (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) affect endothelial cell (EC) shape and F-actin cytoskeleton arrangement in the presence of physiologically relevant wall shear stress (WSS) of 12.5dyn/cm(2).