Evidence for wall shear stress-dependent t-PA release in human conduit arteries: role of endothelial factors and impact of high blood pressure

Author(s):  
Jérémy Bellien ◽  
Michele Iacob ◽  
Vincent Richard ◽  
Julien Wils ◽  
Veronique Le Cam-Duchez ◽  
...  
2019 ◽  
Vol 316 (1) ◽  
pp. C92-C103 ◽  
Author(s):  
Hojin Kang ◽  
Zhigang Hong ◽  
Ming Zhong ◽  
Jennifer Klomp ◽  
Kayla J. Bayless ◽  
...  

Angiogenesis is initiated in response to a variety of external cues, including mechanical and biochemical stimuli; however, the underlying signaling mechanisms remain unclear. Here, we investigated the proangiogenic role of the endothelial mechanosensor Piezo1. Genetic deletion and pharmacological inhibition of Piezo1 reduced endothelial sprouting and lumen formation induced by wall shear stress and proangiogenic mediator sphingosine 1-phosphate, whereas Piezo1 activation by selective Piezo1 activator Yoda1 enhanced sprouting angiogenesis. Similarly to wall shear stress, sphingosine 1-phosphate functioned by activating the Ca2+ gating function of Piezo1, which in turn signaled the activation of the matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase during sprouting angiogenesis. Studies in mice in which Piezo1 was conditionally deleted in endothelial cells demonstrated the requisite role of sphingosine 1-phosphate-dependent activation of Piezo1 in mediating angiogenesis in vivo. These results taken together suggest that both mechanical and biochemical stimuli trigger Piezo1-mediated Ca2+ influx and thereby activate matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase and synergistically facilitate sprouting angiogenesis.


2001 ◽  
Vol 280 (3) ◽  
pp. H1256-H1263 ◽  
Author(s):  
Kelly L. Karau ◽  
Gary S. Krenz ◽  
Christopher A. Dawson

A bifurcating arterial system with Poiseuille flow can function at minimum cost and with uniform wall shear stress if the branching exponent ( z) = 3 [where z is defined by ( D 1) z = ( D 2) z + ( D 3) z ; D 1 is the parent vessel diameter and D 2 and D 3 are the two daughter vessel diameters at a bifurcation]. Because wall shear stress is a physiologically transducible force, shear stress-dependent control over vessel diameter would appear to provide a means for preserving this optimal structure through maintenance of uniform shear stress. A mean z of 3 has been considered confirmation of such a control mechanism. The objective of the present study was to evaluate the consequences of a heterogeneous distribution of z values about the mean with regard to this uniform shear stress hypothesis. Simulations were carried out on model structures otherwise conforming to the criteria consistent with uniform shear stress when z = 3 but with varying distributions of z. The result was that when there was significant heterogeneity in z approaching that found in a real arterial tree, the coefficient of variation in shear stress was comparable to the coefficient of variation in z and nearly independent of the mean value of z. A systematic increase in mean shear stress with decreasing vessel diameter was one component of the variation in shear stress even when the mean z = 3. The conclusion is that the influence of shear stress in determining vessel diameters is not, per se, manifested in a mean value of z. In a vascular tree having a heterogeneous distribution in zvalues, a particular mean value of z (e.g., z = 3) apparently has little bearing on the uniform shear stress hypothesis.


2015 ◽  
Vol 5 (1) ◽  
pp. 90-100 ◽  
Author(s):  
Vitaly Kheyfets ◽  
Mirunalini Thirugnanasambandam ◽  
Lourdes Rios ◽  
Daniel Evans ◽  
Triston Smith ◽  
...  

Author(s):  
Takeshi Tokunaga ◽  
Koji Mori ◽  
Hiroko Kadowaki ◽  
Takashi Saito

Abstract Cardiovascular disease that is one of Non-Communicable Disease accounts for about 25% of death in Japan. Prevention of arteriosclerosis that is a main cause of cardiovascular disease is important. Since an early lesions of arteriosclerosis progress as functional change of an endothelial cell that is uniformly distributed on the luminal surface of a blood vessel, an accurate evaluation of the endothelial cell function is important as prevention of the arteriosclerosis. Although Flow-Mediated Dilation (FMD) is widely used as a diagnosis of the endothelial cell function in clinic, it is an evaluation method that uses a static diameter of a blood vessel. Moreover, it isn’t possible to take into account individual difference of a wall shear stress on the endothelial cell. In previous study, it is found that an evoked hyperemic wall shear stress is a major correlate of %FMD. In order to accurately measure the endothelial cell function, it is necessary to simply assess the hyperemic shear stress during FMD. However, it is difficult to non-invasively measure the hyperemic shear stress on the endothelial cell in clinic. In this study, we focused on a blood pressure data that is obtained non-invasively and formulated a relationship between the pressure and a flow velocity based on the coupled wave theory. And we estimated a hyperemic shear stress by using a blood pressure data that is obtained by a tonometry method in experiment that simulate FMD. As a result of estimating the hyperemic shear stress, it reflected characteristics of blood flow in clinic. It may be necessary to consider the hyperemic pressure fluctuation that is waves including low frequency components. Moreover, the hyperemic pressure fluctuation should not be treated as a waveform that has individually different a static pressure in estimation of the hyperemic wall shear stress.


Author(s):  
Hui Meng ◽  
Sabareesh K. Natarajan ◽  
Eleni Metaxa ◽  
Markus Tremmel ◽  
Ling Gao ◽  
...  

Hemodynamic insult has long been speculated to be a key factor in intracranial aneurysm (IA) formation,1 but the specifics of hemodynamic insult contributing to this process are not understood. Despite other risk factors, IAs are predominantly found at locations associated with unique hemodynamic stress such as at the apices of arterial bifurcations or outer curves, prominent in high wall shear stress (WSS) and wall shear stress gradients (WSSG).2 Furthermore, it appears that increased flow at these locations is required to trigger the initiation of aneurysmal remodeling.3 We have previously shown that increasing flow in the rabbit basilar artery (BA), secondary to common carotid artery (CCA) ligation, resulted in nascent aneurysm development at the basilar terminus (BT).4 However, it is unclear if certain hemodynamic stress thresholds must be exceeded to trigger aneurysmal remodeling, and whether sustained insult is necessary.


2011 ◽  
Vol 32 (3) ◽  
pp. 587-594 ◽  
Author(s):  
Z. Kulcsár ◽  
Á. Ugron ◽  
M. Marosfői ◽  
Z. Berentei ◽  
G. Paál ◽  
...  

2020 ◽  
Vol 88 (2) ◽  
Author(s):  
Yuxi Jia ◽  
Kumaradevan Punithakumar ◽  
Michelle Noga ◽  
Arman Hemmati

Abstract The characteristics of blood flow in an abnormal pediatric aorta with an aortic coarctation and aortic arch narrowing are examined using direct numerical simulations and patient-specific boundary conditions. The blood flow simulations of a normal pediatric aorta are used for comparison to identify unique flow features resulting from the aorta geometrical anomalies. Despite flow similarities compared to the flow in normal aortic arch, the flow velocity decreases with an increase in pressure, wall shear stress, and vorticity around both anomalies. The presence of wall shear stresses in the trailing indentation region and aorta coarctation opposing the primary flow direction suggests that there exist recirculation zones in the aorta. The discrepancy in relative flowrates through the top and bottom of the aorta outlets, and the pressure drop across the coarctation, implies a high blood pressure in the upper body and a low blood pressure in the lower body. We propose using flow manipulators prior to the aortic arch and coarctation to lower the wall shear stress, while making the recirculation regions both smaller and weaker. The flow manipulators form a guide to divert and correct blood flow in critical regions of the aorta with anomalies.


Author(s):  
Biyue Liu ◽  
Jie Zheng ◽  
Richard Bach ◽  
Dalin Tang

There are two major hemodynamic stresses imposed at the blood-arterial wall interface by flowing blood: the wall shear stress (WSS) acting tangentially to the wall, and the wall pressure (WP) acting vertically to the wall. These forces influence the artery wall metabolism and correspond to the local modifications of artery wall thickness, composition, microarchitecture, and compliance [2]. The role of flow wall shear stress in atherosclerosis progression has been under intensive investigation [4], while the impact of local blood pressure on plaque progression has been under-studied.


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