scholarly journals Pattern formation of vascular smooth muscle cells subject to nonuniform fluid shear stress: mediation by gradient of cell density

2003 ◽  
Vol 285 (3) ◽  
pp. H1072-H1080 ◽  
Author(s):  
Shu Q. Liu ◽  
Dalin Tang ◽  
Christopher Tieche ◽  
Paul K. Alkema
Keyword(s):  
Shear Stress ◽  
Smooth Muscle ◽  
Pattern Formation ◽  
Blood Vessels ◽  
Cell Density ◽  
Fluid Shear Stress ◽  
Total Cell ◽  
Fluid Shear ◽  
Nonuniform Fluid ◽  
Total Cell Density

Smooth muscle cells (SMCs) are organized in various patterns in blood vessels. Whereas straight blood vessels mainly contain circumferentially aligned SMCs, curved blood vessels are composed of axially aligned SMCs in regions with vortex blood flow. The vortex flow-dependent feature of SMC alignment suggests a role for nonuniform fluid shear stress in regulating the pattern formation of SMCs. Here, we demonstrate that, in experimental models with vascular polymer implants designed for the observation of neointima formation and SMC migration under defined fluid shear stress, nonuniform shear stress possibly plays a role in regulating the direction of SMC migration and alignment in the neointima of the vascular implant. It was found that fluid shear stress inhibited cell growth, and the presence of nonuniform shear stress influenced the distribution of total cell density and induced the formation of cell density gradients, which in turn directed SMC migration and alignment. In contrast, uniform fluid shear stress in a control model influenced neither the distribution of total cell density nor the direction of SMC migration and alignment. In both the uniform and nonuniform shear models, the gradient of total cell density was consistent with the alignment of SMCs. These observations suggest that nonuniform shear stress may regulate the pattern formation of SMCs, possibly via mediating the gradient of cell density in the neointima of vascular polymer implants.

Pattern formation of vascular smooth muscle cells subject to nonuniform fluid shear stress: role of PDGF-β receptor and Src

2003 ◽  
Vol 285 (3) ◽  
pp. H1081-H1090 ◽  
Author(s):  
Shu Q. Liu ◽  
Christopher Tieche ◽  
Dalin Tang ◽  
Paul Alkema
Keyword(s):  
Shear Stress ◽  
Smooth Muscle ◽  
Cell Density ◽  
Fluid Shear Stress ◽  
Density Gradients ◽  
Dependent Manner ◽  
Fluid Shear ◽  
Polymer Implants ◽  
Β Receptor

Blood vessels are subject to fluid shear stress, a hemodynamic factor that inhibits the mitogenic activities of vascular cells. The presence of nonuniform shear stress has been shown to exert graded suppression of cell proliferation and induces the formation of cell density gradients, which in turn regulate the direction of smooth muscle cell (SMC) migration and alignment. Here, we investigated the role of platelet-derived growth factor (PDGF)-β receptor and Src in the regulation of such processes. In experimental models with vascular polymer implants, SMCs migrated from the vessel media into the neointima of the implant under defined fluid shear stress. In a nonuniform shear model, blood shear stress suppressed the expression of PDGF-β receptor and the phosphorylation of Src in a shear level-dependent manner, resulting in the formation of mitogen gradients, which were consistent with the gradient of cell density as well as the alignment of SMCs. In contrast, uniform shear stress in a control model elicited an even influence on the activity of mitogenic molecules without modulating the uniformity of cell density and did not significantly influence the direction of SMC alignment. The suppression of the PDGF-β receptor tyrosine kinase and Src with pharmacological substances diminished the gradients of mitogens and cell density and reduced the influence of nonuniform shear stress on SMC alignment. These observations suggest that PDGF-β receptor and Src possibly serve as mediating factors in nonuniform shear-induced formation of cell density gradients and alignment of SMCs in the neointima of vascular polymer implants.

scholarly journals Assessment of the Effects of Bisphenol A on Dopamine Synthesis and Blood Vessels in the Goldfish Brain

2019 ◽  
Vol 20 (24) ◽  
pp. 6206 ◽  
Author(s):  
Qing Wang ◽  
Fangmei Lin ◽  
Qi He ◽  
Xiaochun Liu ◽  
Shiqiang Xiao ◽  
...  
Keyword(s):  
Shear Stress ◽  
Bisphenol A ◽  
Blood Vessels ◽  
Fluid Shear Stress ◽  
Dopamine Neurons ◽  
Dopamine Synthesis ◽  
Exposure Group ◽  
Fluid Shear ◽  
Toxicological Studies ◽  
The Brain

Bisphenol A (BPA) is an abundant contaminant found in aquatic environments. While a large number of toxicological studies have investigated the effects of BPA, the potential effects of BPA exposure on fish brain have rarely been studied. To understand how BPA impacts goldfish brains, we performed a transcriptome analysis of goldfish brains that had been exposed to 50 μg L−1 and 0 μg L−1 BPA for 30 days. In the analysis of unigene expression profiles, 327 unigenes were found to be upregulated and 153 unigenes were found to be downregulated in the BPA exposure group compared to the control group. Dopaminergic signaling pathway-related genes were significantly downregulated in the BPA exposure group. Furthermore, we found that serum dopamine concentrations decreased and TUNEL (terminal deoxynucleotidyl transferase 2-deoxyuridine, 5-triphosphate nick end labeling) staining was present in dopamine neurons enriched regions in the brain after BPA exposure, suggesting that BPA may disrupt dopaminergic processes. A KEGG analysis revealed that genes involved in the fluid shear stress and atherosclerosis pathway were highly significantly enriched. In addition, the qRT-PCR results for fluid shear stress and atherosclerosis pathway-related genes and the vascular histology of the brain showed that BPA exposure could damage blood vessels and induce brain atherosclerosis. The results of this work provide insights into the biological effects of BPA on dopamine synthesis and blood vessels in goldfish brain and could lay a foundation for future BPA neurotoxicity studies.

Negative regulation of vascular smooth muscle cell migration by blood shear stress

2007 ◽  
Vol 292 (2) ◽  
pp. H928-H938 ◽  
Author(s):  
Jeremy Goldman ◽  
Lin Zhong ◽  
Shu Q. Liu
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vein Graft ◽  
Fluid Shear Stress ◽  
Fluid Shear ◽  
Vein Grafts ◽  
Polymer Implant

Vortex blood flow with reduced blood shear stress in a vein graft has been hypothesized to promote smooth muscle cell (SMC) migration and intimal hyperplasia, pathological events leading to vein graft restenosis. To demonstrate that blood shear stress regulates these processes, we developed a modified vein graft model where the SMC response to reduced vortex blood flow was compared with that of control vein grafts. Vortex blood flow induced SMC migration and neointimal hyperplasia in control vein grafts, whereas reduction of vortex blood flow in the modified vein graft strongly suppressed these effects. A venous polymer implant with known fluid shear stress was employed to clarify the molecular mechanism of shear-dependent SMC migration in vivo. In the polymer implant, the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and myosin light chain kinase (MLCK), found primarily in SMCs, increased from day 3 to day 5 and returned toward the control level from day 5 to day 10, with the peak phosphorylation associated with the maximal speed of SMC migration. Treatment with PD-98059 (an inhibitor specific to the ERK1/2 activator MEK1/2) significantly suppressed the phosphorylation of MLCK, suggesting a role for ERK1/2 in regulating the activity of MLCK. Treatment with PD-98059 or ML-7 (an inhibitor specific to MLCK) reduced shear stress-dependent SMC migration, resulting in an SMC distribution independent of fluid shear stress. These results suggest that fluid shear stress regulates SMC migration via the mediation of ERK1/2 and MLCK.

Endothelial Cell Elongation Impacts Thrombogenicity Independent of Fluid Shear Stress.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1886-1886
Author(s):  
Keri B Vartanian ◽  
Brad J Blakley ◽  
Owen JT McCarty ◽  
Stephen Hanson ◽  
Monica T Hinds
Keyword(s):  
Gene Expression ◽  
Shear Stress ◽  
Blood Vessels ◽  
Tissue Factor ◽  
Platelet Adhesion ◽  
Surface Engineering ◽  
Fluid Shear Stress ◽  
Cell Function ◽  
Fluid Shear ◽  
Atherosclerotic Vascular Disease

Abstract Atherosclerotic vascular disease and dysfunction of endothelial cells (ECs), which form the continuous lining of blood vessels, preferentially develop in regions where blood vessels are bifurcated and curved. In these regions, ECs are exposed to low, oscillatory fluid shear stress (FSS), are cobblestone in morphology, and have an athero-prone phenotype. In contrast, in regions where FSS is high and unidirectional, ECs are elongated parallel to the direction of flow and have an athero-protective phenotype. Although previous research has correlated FSS with EC morphology and phenotype, the effects of dramatic changes in cell morphology alone, i.e., in the absence of FSS differences, on EC functions remain largely unknown. To determine the role of EC shape on cell function, we investigated the regulation of EC hemostatic functions, an important measure of EC dysfunction and atherosclerosis, by elongated and cobblestone ECs (with shape independent of FSS). To separate EC shape from FSS-induced effects, surface engineering was used to create elongated ECs on micropatterned collagen I lanes (25 μm wide with 100 μm spacing). By 24 hrs, ECs elongated on these micropatterned lanes had a comparable shape index and cytoskeletal alignment as ECs elongated by exposure to 24 hrs of 12.5 dyn/cm2 FSS. qtPCR was used to determine the gene expression of the following markers of coagulant/hemostatic functions: tissue factor (TF), tissue factor pathway inhibitor (TFPI), endothelial nitric oxide synthase (eNOS), thrombomodulin (TM), and von Willebrand Factor (vWF). PCR results indicated that EC elongation alone upregulated expression of TF (1.41 ± 0.28) and decreased expression of eNOS (0.78 ± 0.07). vWF was downregulated (0.59 ± 0.11). Micropattern elongated ECs expressed TFPI and TM at levels comparable to cobblestoneappearing ECs (1.04 ± 0.08 and 1.12 ± 0.04, respectively). To determine whether these changes in gene expression had functional consequences, the generation of thrombin (factor X activation, FXa) and platelet adhesion were studied. Micropattern elongated ECs were able to convert more FX to FXa per cell compared to cobblestone ECs (0.88 ± 0.20 and 0.065 ± 0.01 pg/cell, respectively), indicating an increase in TF activity. This data is consistent with the increased TF gene expression seen in micropattern elongated ECs. Platelet adhesion studies also suggested a thrombogenic phenotype for micropattern elongated ECs, with more platelets adhering and spreading per cell on elongated (8.82 ± 1.47) versus cobblestone (4.64 ± 1.49) ECs. Overall, these findings suggest that EC shape is an independent variable that can regulate cell hemostatic functions, such as thrombotic potential. Surprisingly, elongated ECs exhibited a more thrombogenic phenotype, findings that contrast results obtained with FSS-elongated ECs, both in vitro and in vivo. Thus, both cell shape and FSS may play important and in some instances opposing roles in regulating EC hemostatic functions in the maintenance of vascular integrity.

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