Shear Stress Attenuates Inward Remodeling in Cultured Mouse Thoracodorsal Arteries in an eNOS-Dependent, but Not Hemodynamic Manner, and Increases Cx37 Expression

Abstract

<b><i>Background:</i></b> Arteries chronically constricted in culture remodel to smaller diameters. Conversely, elevated luminal shear stress (SS) promotes outward remodeling of arteries in vivo and prevents inward remodeling in culture in a nitric oxide synthase (NOS)-dependent manner. <b><i>Objectives:</i></b> To determine whether SS-induced prevention of inward remodeling in cultured arteries is specifically eNOS-dependent and requires dilation, and whether SS alters the expression of eNOS and other genes potentially involved in remodeling. <b><i>Methods:</i></b> Female mouse thoracodorsal arteries were cannulated, pressurized to 80 mm Hg, and cultured for 2 days with low SS (<7 dyn/cm<sup>2</sup>), high SS (≥15 dyn/cm<sup>2</sup>), high SS + L-NAME (NOS inhibitor, 10<sup>–4</sup> M), or high SS in arteries from eNOS–/– mice. In separate arteries cultured 1 day with low or high SS, eNOS and connexin (Cx) 37, Cx40, and Cx43 mRNA were assessed with real-time PCR. <b><i>Results:</i></b> High SS caused little change in passive diameters after culture (–4.7 ± 2.0%), which was less than low SS (–18.9 ± 1.4%; <i>p</i> < 0.0001), high SS eNOS–/– (–18.0 ± 1.5; <i>p</i> < 0.001), or high SS + L-NAME (–12.0 ± 0.6%; nonsignificant) despite similar constriction during culture. Cx37 mRNA expression was increased (<i>p</i> < 0.05) with high SS, but other gene levels were not different. <b><i>Conclusions:</i></b> eNOS is involved in SS-induced prevention of inward remodeling in cultured small arteries. This effect does not require NO-mediated dilation. SS increased Cx37.

Activation of Smad2/3 signaling by low fluid shear stress mediates artery inward remodeling

“…The best studied gene target of the MEKK3-Klf2 axis is eNOS (NOS3), which is a critical mediator of vasodilation and therefore a top candidate for opposing inward remodeling. eNOS is a well-validated Klf2 target gene that has been implicated in the regulation of artery lumen diameter (23,24). Two different siRNAs against eNOS gave nearly complete KD of eNOS but had no effect on Smad2/3 nuclear localization in high flow (SI Appendix, Fig.…”

Cardiovascular, Metabolic and Inflammatory Changes after Ovariectomy and Estradiol Substitution in Hereditary Hypertriglyceridemic Rats

“…The explanation for this negative finding could be that the change of Cx37 gene expression was not yet detectable relatively soon after ovariectomy and could be relatively delayed compared to the change of the expression of gene for Nos3 . In addition, changes of Cx37 activity and gap junctions were described mainly in the smaller vessels including mice and dependent on changes of shear stress [ 25 , 26 ]. Therefore, in abdominal aorta, the changes of shear stress in rats compared to mice could be less pronounced in this location due simply to larger diameter and in contrast to Nos3 gene, Cx37 gene could be less sensitive to these changes.…”