Effects of different types of fluid shear stress on endothelial cell proliferation and survival

Abstract

We attempted to clarify the effect of different types of shear stress on endothelial cell (EC) proliferation and survival. Bovine aortic ECs were subjected to either steady laminar, 1 Hz pulsatile, or 1 Hz to and fro shear at 14 dyne/cm(2). % of BrdU positive EC was 14.3 +/- 1.6% in steady, 21.5 +/- 3.2% in pulsatile, and 11.4 +/- 2.4% in to and fro after 4 h, respectively (P < 0.05). Pulsatile shear compared with static control. Rapamycin reduced BrdU incorporation in all shear regimens (P < 0.001). However, it was still higher in EC exposed to pulsatile shear than the other regimens (P < 0.005). PD98059 completely abolished the increased BrdU incorporation in all shear regimens, including pulsatile shear. Pulsatile shear had significantly elevated ERK1/2 phosphorylation at 5 min compared with steady (P < 0.05) and to and fro shear (P < 0.01) while there was no significant difference in pp70(S6k) phosphorylation between any shear regimen. The ratio of apoptotic cells in serum deprived EC in the presence of steady laminar, pulsatile and to and fro shear for 4 h were 2.7 +/- 0.78%, 2.7 +/- 0.42%, and 2.9 +/- 0.62%, respectively while after the addition of serum for 4 h, it was 4.3 +/- 0.73%. All shear regimens phosphorylated AKT in a time-dependent manner with no significant difference between regimens. Our results demonstrate that different types of shear stress regimens have different effects on EC and may account for the variable response of EC to hemodynamics in the circulation.

Effect of Frequency of Uniform and Disturbed Pulsatility Flow on Tissue Factor Expression of Human Umbilical Vein Endothelial Cells

“…Likewise, we showed that bovine aortic ECs exposed to pulsatile flow frequencies of 0.5 and 1.0 Hz, but not 1.5 Hz, exhibited elongated morphologies and oriented with the direction of flow [22]. Our laboratory also demonstrated that 1 Hz but not 0.1, 0.5, or 1.5 Hz was optimal for bovine aortic ECs proliferation when exposed to PFF [8]. Interestingly, frequency had no effect on proliferation of bovine aortic ECs exposed to TFF [8].…”

“…Our laboratory also demonstrated that 1 Hz but not 0.1, 0.5, or 1.5 Hz was optimal for bovine aortic ECs proliferation when exposed to PFF [8]. Interestingly, frequency had no effect on proliferation of bovine aortic ECs exposed to TFF [8]. Other investigators have also reported that anti-inflammatory responses of porcine aortic ECs exposed to 1 Hz forward flow are reversed at 2 Hz [23].…”

“…Our laboratory has investigated the role of mechanical forces on ECs [7][8][9][10], and we have previously reported a significant increase in TF expression of ECs exposed to disturbed flow [7,11,12]. The purpose of this study is to compare the effect of frequency of disturbed and uniform flow on EC expression of TF.…”

Surgically implantable magnetic resonance angiography coils improve resolution to allow visualization of blood flow dynamics

“…In particular, mouse models are extremely useful, as several genetic mutations that influence arterial development and behavior have been described. 32,33 Ultimately, wall shear stress is the result of blood flow against the arterial wall, and has been shown to influence endothelial 9,12 and smooth muscle cell behavior. 5,11 Previous investigators have used computational fluid dynamics to estimate wall shear stress in blood vessels using MRI, 34 and this technique could be combined with coil-assisted imaging to allow calculation of wall shear stress in small animal models.…”

“…1,5,6 Often cell types are isolated and exposed to a single type of flow in an in vitro model such as laminar, to-and-fro, orbital or more complicated patterns. These in vitro studies have led to the identification of several molecular mediators that respond to different flow patterns, [7][8][9][10][11] and recently a shear stress receptor for endothelial cells has been identified. 12 One limitation of these models is that vascular disease is a complex process, involving multiple cell types and interactions between cells and molecular mediators.…”