• Molecules and Cells
• /
• 제38권10호
• /
• pp.851-858
• /
• 2015

Disturbed blood flow with low-oscillatory shear stress (OSS) is a predominant atherogenic factor leading to dysfunctional endothelial cells (ECs). Recently, it was found that disturbed flow can directly induce endoplasmic reticulum (ER) stress in ECs, thereby playing a critical role in the development and progression of atherosclerosis. Ursodeoxycholic acid (UDCA), a naturally occurring bile acid, has long been used to treat chronic cholestatic liver disease and is known to alleviate endoplasmic reticulum (ER) stress at the cellular level. However, its role in atherosclerosis remains unexplored. In this study, we demonstrated the anti-atherogenic activity of UDCA via inhibition of disturbed flow-induced ER stress in atherosclerosis. UDCA effectively reduced ER stress, resulting in a reduction in expression of X-box binding protein-1 (XBP-1) and CEBP-homologous protein (CHOP) in ECs. UDCA also inhibits the disturbed flow-induced inflammatory responses such as increases in adhesion molecules, monocyte adhesion to ECs, and apoptosis of ECs. In a mouse model of disturbed flow-induced atherosclerosis, UDCA inhibits atheromatous plaque formation through the alleviation of ER stress and a decrease in adhesion molecules. Taken together, our results revealed that UDCA exerts anti-atherogenic activity in disturbed flow-induced atherosclerosis by inhibiting ER stress and the inflammatory response. This study suggests that UDCA may be a therapeutic agent for prevention or treatment of atherosclerosis.

• Molecules and Cells
• /
• 제37권6호
• /
• pp.435-440
• /
• 2014

Hemodynamic shear stress, the frictional force acting on vascular endothelial cells, is crucial for endothelial homeostasis under normal physiological conditions. When discussing blood flow effects on various forms of endothelial (dys)function, one considers two flow patterns: steady laminar flow and disturbed flow because endothelial cells respond differently to these flow types both in vivo and in vitro. Laminar flow which exerts steady laminar shear stress is atheroprotective while disturbed flow creates an atheroprone environment. Emerging evidence has provided new insights into the cellular mechanisms of flowdependent regulation of vascular function that leads to cardiovascular events such as atherosclerosis, atherothrombosis, and myocardial infarction. In order to study effects of shear stress and different types of flow, various models have been used. In this review, we will summarize our current views on how disturbed flow-mediated signaling pathways are involved in the development of atherosclerosis.

• Molecules and Cells
• /
• 제41권11호
• /
• pp.964-970
• /
• 2018

Atherosclerosis preferentially involves in prone area of low and disturbed blood flow while steady and high levels of laminar blood flow are relatively protected from atherosclerosis. Disturbed flow induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). ER stress is caused under stress that disturbs the processing and folding of proteins resulting in the accumulation of misfolded proteins in the ER and activation of the UPR. Prolonged or severe UPR leads to activate apoptotic signaling. Recent studies have indicated that disturbed flow significantly up-regulated $p-ATF6{\alpha}$, $p-IRE1{\alpha}$, and its target spliced XBP-1. However, the role of laminar flow in ER stress-mediated endothelial apoptosis has not been reported yet. The present study thus investigated the role of laminar flow in ER stress-dependent endothelial cell death. The results demonstrated that laminar flow protects ER stress-induced cleavage forms of PARP-1 and caspase-3. Also, laminar flow inhibits ER stress-induced $p-eIF2{\alpha}$, ATF4, CHOP, spliced XBP-1, ATF6 and JNK pathway; these effects are abrogated by pharmacological inhibition of PI3K with wortmannin. Finally, nitric oxide affects thapsigargin-induced cell death in response to laminar flow but not UPR. Taken together, these findings indicate that laminar flow inhibits UPR and ER stress-induced endothelial cell death via PI3K/Akt pathway.

• 한국농공학회지
• /
• 제35권3호
• /
• pp.74-80
• /
• 1993

Runoff simulation tests to investigate the flow mechanics of nonsuomerged overland flow in a natural grass intervening land system were condueted and a modified kinematic wave overland runoff model developed by Choi et al. (1993) was verified. Nonhomogeneity and heterogeneity of the soil, slope, local topography, infiltration, grass density, and the density and activity of the soil microhes and wild animals were the major factors affecting the flow. Streamlines were disturbed by grass stems and small concentrated flows due to the disturbed streamlines and local topography were observed a lot. Relatively larger concentrated flows were observed where bundles of grass were dominant than where individual grasses were growing. Predicted hydrographs were agreed verv well with measured hydrographs. Since the modified model considers grass density in computing flow depth and hydraulic radius, it can be better than existing kinematic wave model if it were used to route nonpoint source pollutant attenuation processes in many grass intervening land systems.

• 대한기계학회:학술대회논문집
• /
• 대한기계학회 2004년도 춘계학술대회
• /
• pp.1987-1992
• /
• 2004

Hemodynamics behavior of the blood flow is influenced by the presence of the arterial stenosis. If stenosis is present in an artery, normal blood flow is disturbed. In the present study, characteristics of steady and pulsatile flow of non-Newtonian fluid, the effects of stenosised geometry are analyzed by numerical simulation. One interesting point is that non-symmetric solutions were obtained at severity stenosis, although the stenosis and the boundary condition were all axisymmetric.

• 대한기계학회:학술대회논문집
• /
• 대한기계학회 2002년도 학술대회지
• /
• pp.691-694
• /
• 2002

The most unstable situation of laminar plane Poiseuille flow for transition to turbulence is investigated by using a pseudo-spectral method. A number of various disturbance modes are tested and it is found that the flow is the most unstable when it is disturbed by an oblique wave with an angle of $29.7^{\circ}$.

• 한국해양공학회:학술대회논문집
• /
• 한국해양공학회 2000년도 추계학술대회 논문집
• /
• pp.68-72
• /
• 2000

In the present paper, the numerical calculations for the viscous duct flow of water jet propulsion systems ship are carried out. The governing equation, incompressible Navier-Stokes equation, is discretized and analysed by a Method with the stcandard turbulence modeling. For the calculations the duct flow which h e intake flows disturbed by the ship, the results dcuhted by the potenti used Numerical results show fairly good agreement with the experimental data

• Journal of Advanced Marine Engineering and Technology
• /
• 제24권6호
• /
• pp.120-127
• /
• 2000

This study is concerned with evaluating the effects of acoustic excitation on the development of two stream mixing layer generated by split plate. The ratios of two velocities U1 and U2 either side of the splitter plate were such that $U_1/U_2$=1.0 (uniform flow) or $U_1/U_2$<1.0(shear flow). The mixing layers were disturbed acoustically through the edge of split plate. Quantitative data were obtained with hot-wire anemometry. Flow visualization with smoke-wire was also employed for qualitative study. the results show that the large scale structures of mixing layers are strongly affected by excitation frequency and amplitude in both uniform and shear flows. The maximum streamwise and vertical turbulent intensities of the excited flow fields are apt to be decreased as compared with those of without excitation. The flow characteristics of uniform flow are more influenced by acoustic excitation than those of shear flow.

• 대한기계학회논문집
• /
• 제12권3호
• /
• pp.497-504
• /
• 1988

본 연구에서는 트랙션이 없는 커스프 균열에 적용한 방법을 확장하여 무한대 에서 균일열유동을 받는 무한체내에 하이포사이클로이드형(hypocycloid type), 대칭이 기형(symmetric airfoil type), 대칭입술형(symmetric lip type) 강체 함유물이 존재 하고 그 표면은 단열되거나 상대온도가 영으로 주어지는 경우에 대해서 열응력세기계 수(thermal stress intensity factor이하에서 TSIF로 표기함)를 유도하고자 한다.

• 대한기계학회논문집B
• /
• 제25권11호
• /
• pp.1476-1482
• /
• 2001

Turbulent boundary layer over a flat plate was disturbed by installing an elliptic cylinder with an axis ratio of AR=2. For comparison, the same experiment was carried out for a circular cylinder having the same vertical height. The surface pressure and the heat transfer coefficient on the flat plate were measured with varying the gap distance between the elliptic cylinder and the flat plate. The mean velocity and the turbulent intensity profile of the streamwise velocity component were measured using a hot-wire anemometry. As a result, the flow structure and the local heat transfer rate were modified by the interaction between the cylinder wake and the turbulent boundary layer as a function of the critical gap ratio where the regular vortices start to shed. For the elliptic cylinder, the critical gap ratio is increased and the surface pressure on the flat plate is recovered rapidly at downstream location, compared with the equivalent circular cylinder. The maximum heat transfer rate occurs at the gap ratio of G/B = 0.5, where the flow interaction between the lower shear layer of the cylinder wake and the turbulent boundary layer is strong.