共查询到20条相似文献,搜索用时 15 毫秒
1.
Cummins PM von Offenberg Sweeney N Killeen MT Birney YA Redmond EM Cahill PA 《American journal of physiology. Heart and circulatory physiology》2007,292(1):H28-H42
The vascular endothelium is a dynamic cellular interface between the vessel wall and the bloodstream, where it regulates the physiological effects of humoral and biomechanical stimuli on vessel tone and remodeling. With respect to the latter hemodynamic stimulus, the endothelium is chronically exposed to mechanical forces in the form of cyclic circumferential strain, resulting from the pulsatile nature of blood flow, and shear stress. Both forces can profoundly modulate endothelial cell (EC) metabolism and function and, under normal physiological conditions, impart an atheroprotective effect that disfavors pathological remodeling of the vessel wall. Moreover, disruption of normal hemodynamic loading can be either causative of or contributory to vascular diseases such as atherosclerosis. EC-matrix interactions are a critical determinant of how the vascular endothelium responds to these forces and unquestionably utilizes matrix metalloproteinases (MMPs), enzymes capable of degrading basement membrane and interstitial matrix molecules, to facilitate force-mediated changes in vascular cell fate. In view of the growing importance of blood flow patterns and mechanotransduction to vascular health and pathophysiology, and considering the potential value of MMPs as therapeutic targets, a timely review of our collective understanding of MMP mechanoregulation and its impact on the vascular endothelium is warranted. More specifically, this review primarily summarizes our current knowledge of how cyclic strain regulates MMP expression and activation within the vascular endothelium and subsequently endeavors to address the direct and indirect consequences of this on vascular EC fate. Possible relevance of these phenomena to vascular endothelial dysfunction and pathological remodeling are also addressed. 相似文献
2.
Vascular endothelial cells are located at the innermost layer of the blood vessel wall and are always exposed to three different mechanical forces: shear stress due to blood flow, hydrostatic pressure due to blood pressure and cyclic stretch due to vessel deformation. It is well known that endothelial cells respond to these mechanical forces and change their shapes, cytoskeletal structures and functions. In this review, we would like to mainly focus on the effects of shear stress and hydrostatic pressure on endothelial cell morphology. After applying fluid shear stress, cultured endothelial cells show marked elongation and orientation in the flow direction. In addition, thick stress fibers of actin filaments appear and align along the cell long axis. Thus, endothelial cell morphology is closely related to the cytoskeletal structure. Further, the dynamic course of the morphological changes is shown and the related events such as changes in mechanical stiffness and functions are also summarized. When endothelial cells were exposed to hydrostatic pressure, they exhibited a marked elongation and orientation in a random direction, together with development of centrally located, thick stress fibers. Pressured endothelial cells also exhibited a multilayered structure with less expression of VE-cadherin unlike under control conditions. Simultaneous loading of hydrostatic pressure and shear stress inhibited endothelial cell multilayering and induced elongation and orientation of endothelial cells with well-developed VE-cadherin in a monolayer, which suggests that for a better understanding of vascular endothelial cell responses one has to take into consideration the combination of the different mechanical forces such as exist under in vivo mechanical conditions. 相似文献
3.
White CR Frangos JA 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2007,362(1484):1459-1467
As the inner lining of the vessel wall, vascular endothelial cells are poised to act as a signal transduction interface between haemodynamic forces and the underlying vascular smooth-muscle cells. Detailed analyses of fluid mechanics in atherosclerosis-susceptible regions of the vasculature reveal a strong correlation between endothelial cell dysfunction and areas of low mean shear stress and oscillatory flow with flow recirculation. Conversely, steady shear stress stimulates cellular responses that are essential for endothelial cell function and are atheroprotective. The molecular basis of shear-induced mechanochemical signal transduction and the endothelium's ability to discriminate between flow profiles remains largely unclear. Given that fluid shear stress does not involve a traditional receptor/ligand interaction, identification of the molecule(s) responsible for sensing fluid flow and mechanical force discrimination has been difficult. This review will provide an overview of the haemodynamic forces experienced by the vascular endothelium and its role in localizing atherosclerotic lesions within specific regions of the vasculature. Also reviewed are several recent lines of evidence suggesting that both changes in membrane microviscosity linked to heterotrimeric G proteins, and the transmission of tension across the cell membrane to the cell-cell junction where known shear-sensitive proteins are localized, may serve as the primary force-sensing elements of the cell. 相似文献
4.
Radial artery wall shear stress evaluation in patients with arteriovenous fistula for hemodialysis access 总被引:1,自引:0,他引:1
Remuzzi A Ene-Iordache B Mosconi L Bruno S Anghileri A Antiga L Remuzzi G 《Biorheology》2003,40(1-3):423-430
It has been extensively documented that changes in blood flow induce vascular remodeling and this phenomenon seems to be correlated to the shear forces imposed on the vessel wall by motion of blood. Wall shear stress, the tractive force that acts on the endothelium, has been shown to influence endothelial cell function. To study changes in wall shear stress that develop on the vessel wall upon changes of blood flow, we set up a technique that allows estimation of shear stress in the radial artery of patients on chronic hemodialysis therapy. The technique is based on color-flow Doppler examination of the radial artery before and after surgical creation of radiocephalic fistula for hemodialysis. Calculation of time function wall shear stress and blood flow rate in the radial artery is performed on the basis of arterial diameter, center-line velocity waveform and blood viscosity, using a numerical method developed according to Womersley's theory for pulsatile flow in tubes. The results presented confirm that the model developed is suitable for calculation of the wall shear stress that develops in the radial artery of patients before and after surgical creation of an arteriovenous fistula for hemodialysis. This methodology was developed for characterization of wall shear stress in the radial artery but may be well applied to other vessels that can be examined by echo-Doppler technique. 相似文献
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6.
Markus Tremmel Jianping Xiang Yiemeng Hoi John Kolega Adnan H. Siddiqui J. Mocco Hui Meng 《Biomechanics and modeling in mechanobiology》2010,9(4):421-434
Hemodynamic forces play critical roles in vascular pathologies such as atherosclerosis, aneurysms, and stenosis. However, detailed relationships between the specific in vivo hemodynamic microenvironment and vascular responses leading to the triggering or exacerbation of pathological remodeling of the vessel remain elusive. We have developed a hemodynamics-biology co-mapping technique that enables in situ correlation between the in vivo blood flow field and vascular changes secondary to hemodynamic insult. The hemodynamics profile is obtained from computational fluid dynamics simulation within the vascular geometry reconstructed from three-dimensional in vivo images, whereas the vascular response is obtained from histology or immunohistochemistry on harvested vascular tissue. The hemodynamics field is virtually sectioned in the histological slicing planes and digitally co-mapped with the histological images, thereby enabling correlation of the specific local vascular responses with the inciting hemodynamic stresses. We demonstrate application of this technique to rabbit basilar terminus subjected to elevated flow. Morphological changes at the basilar terminus 5 days after the flow increase were co-mapped with the initial wall shear stress and wall shear stress gradient distributions, from which localization of destructive remodeling in a specific hemodynamic zone was noticed. This method paves the way for further investigations to determine the connection between in vivo mechanical stimuli and biological responses, such as initiation of aneurysmal remodeling. 相似文献
7.
Vascular functions are regulated not only by chemical mediators, such as hormones, cytokines, and neurotransmitters, but by
mechanical hemodynamic forces generated by blood flow and blood pressure. The mechanical force-mediated regulation is based
on the ability of vascular cells, including endothelial cells and smooth muscle cells, to recognize fluid mechanical forces,
i.e., the shear stress produced by flowing blood and the cyclic strain generated by blood pressure, and to transmit the signals
into the cell interior, where they trigger cell responses that involve changes in cell morphology, cell function, and gene
expression. Recent studies have revealed that immature cells, such as endothelial progenitor cells (EPCs) and embryonic stem
(ES) cells, as well as adult vascular cells, respond to fluid mechanical forces. Shear stress and cyclic strain promote the
proliferation and differentiation of EPCs and ES cells into vascular cells and enhance their ability to form new vessels.
Even more recently, attempts have been made to apply fluid mechanical forces to EPCs and ES cells cultured on polymer tubes
and develop tissue-engineered blood vessel grafts that have a structure and function similar to that of blood vessels in vivo.
This review summarizes the current state of knowledge concerning the mechanobiological responses of stem/progenitor cells
and its potential applications to tissue engineering. 相似文献
8.
Differential responsiveness of vascular endothelial cells to different types of fluid mechanical shear stress 总被引:5,自引:0,他引:5
Early atherosclerotic lesions localize preferentially, in arterial regions exposed to low flow, oscillatory flow, or both;
however, the cellular basis of this observation remains to be determined. Atherogenesis involves dysfunction of the vascular
endothelium, the cellular monolayer lining the inner surfaces of blood vessels. How low flow, oscillatory flow, or both may
lead to endothelial dysfunction remains unknown. Over the past two decades, fluid mechanical shear (or frictional) stress
has been shown to intricately regulate the structure and function of vascular endothelial cells (ECs). Furthermore, recent
data indicate that beyond being merely responsive to shear stress, ECs are able to distinguish among and respond differently
to different types of shear stress. This review focuses on EC differential responses to different types of steady and unsteady
shear stress and discusses the implications of these responses for the localization of early atherosclerotic lesions. The
mechanisms by which endothelial differential responsiveness to different types of flow may occur are also discussed. 相似文献
9.
Hemodynamic forces associated with blood flow play a vital role in the endothelial regulation of vascular tone, remodeling and the initiation and progression of vascular diseases such as atherosclerosis and hypertension. Crucial elements in endothelium-mediated events within the blood vessel are bioactive peptide signals and their associated hydrolytic enzymes. This review examines the relationship between hemodynamic forces such as shear stress and cyclic strain, and an important group of peptide-degrading enzymes within the endothelium, the thermolysin-like zinc metallopeptidases. 相似文献
10.
Control of endothelial cell gene expression by flow 总被引:13,自引:0,他引:13
The vessel wall is constantly subjected to, and affected by, the stresses resulting from the hemodynamic stimuli of transmural pressure and flow. At the interface between blood and the vessel wall, the endothelial cell plays a crucial role in controlling vessel structure and function in response to changes in hemodynamic conditions. Using bovine aortic endothelium monolayers, we show that fluid shear stress causes simultaneous differential regulation of endothelial-derived products. We also report that the downregulation of endothelin-1 mRNA by flow is a reversible process, and through the use of uncharged dextran supplementation demonstrate it to be shear stress-rather than shear rate-dependent. Recent work on the effect of fluid shear stress on endothelial cell gene expression of a number of potent endothelial products is reviewed, including vasoactive substances, autocrine and paracrine growth factors, thrombosis/fibrinolysis modulators, chemotactic factors, surface receptors and immediate-early genes. The encountered patterns of gene expression responses are classified into three categories: a transient increase with return to baseline (type I), a sustained increase (type II) and a biphasic response consisting of an early transient increase of varying extent followed by a pronounced and sustained decrease (type III). The importance of the dynamic character of the flow stimulus and the magnitude dependence of the response are presented. Potential molecular mechanisms of shear-induced gene regulation, including putative shear stress response elements (SSRE), are discussed. These results suggest exquisite modulation of endothelial cell phenotype by local fluid shear stress and may offer insight into the mechanism of flow-dependent vascular remodeling and the observed propensity of atherosclerosis formation around bifurcations and areas of low shear stress. 相似文献
11.
The link between atherosclerosis and regions of disturbed flow and low wall shear stress is now firmly established, but the causal mechanisms underlying the link are not yet understood. It is now recognised that the endothelium is not simply a passive barrier between the blood and the vessel wall, but plays an active role in maintaining vascular homeostasis and participates in the onset of atherosclerosis. Calcium signalling is one of the principal intracellular signalling mechanisms by which endothelial cells (EC) respond to external stimuli, such as fluid shear stress and ligand binding. Previous studies have separately modelled mass transport of chemical species in the bloodstream and calcium dynamics in EC via the inositol trisphosphate (IP(3)) signalling pathway. We review existing models of these two phenomena, before going on to integrate the two components to provide an inclusive new model for the calcium response of the endothelium in an arbitrary vessel geometry. This enables the combined effects of fluid flow and biochemical stimulation on EC to be investigated and is the first time spatially varying, physiological fluid flow-related environmental factors have been combined with intracellular signalling in a mathematical model. Model results show that low endothelial calcium levels in the area of disturbed flow at an arterial widening may be one contributing factor to the onset of vascular disease. 相似文献
12.
Mel'kumiants AM Balashov SA Kartamyshev SP 《Rossi?skii fiziologicheski? zhurnal imeni I.M. Sechenova / Rossi?skaia akademiia nauk》2004,90(6):693-704
The effect of control of arterial diameter by the shear stress at the endothelium on noradrenaline-induced constriction of femoral vascular bed was investigated in anaesthetised cats. We compared noradrenaline-induced responses during the perfusion of the hindlimb at a constant blood flow and at a constant pressure as vasoconstriction is accompanied by an increase in wall shear stress only in the former case. We found that the same concentration of noradrenaline at a constant flow caused an augmentation of vascular resistance that was considerably smaller than at a constant pressure perfusion. This difference was almost eliminated after either removal of the endothelium or selective impairment of the endothelial sensitivity to the shear stress. These findings demonstrate that the control of arterial smooth muscle tone at a constant blood flow by shear stress at the endothelium does weaken noradrenaline-induced vasoconstriction. 相似文献
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Shirin Saberianpour Mohamad Hadi Saeed modaghegh Hamidreza Rahimi Mohammad Mahdi Kamyar 《Biophysical reviews》2021,13(1):139
Varicose veins are the most common vascular disease in humans. Veins have valves that help the blood return gradually to the heart without leaking blood. When these valves become weak, blood and fluid collect and pool by pressing against the walls of the veins, causing varicose veins. In the cardiovascular system, mechanical forces are important determinants of vascular homeostasis and pathological processes. Blood vessels are constantly exposed to a variety of hemodynamic forces, including shear stress and environmental strains caused by the blood flow. In varicose veins within the leg, venous blood pressure rises in the vein of the lower extremities due to prolonged standing, creating a peripheral tension in the vessel wall thereby causing mechanical stimulation of endothelial cells and vascular smooth muscle. Studies have shown that long-term increased exposure to vascular wall tension is associated with the overexpression of HIF-1α and HIF-2α and increased levels of MMP-2 and MMP-9, thereby reducing venous contraction and progressive venous dilatation, which is involved in the development of varicose veins. Following the expression of metalloproteinase, the expression of type 1 collagen increases, and the amount of type 3 collagen decreases. Therefore, collagen imbalance will cause the varicose veins to not stretch. Loss of structural proteins (type 3 collagen and elastin) in the vessel wall causes the loss of the biophysical properties of the varicose vein wall. This review article tries to elaborate on the effect of mechanical forces and sensors of these forces on the vascular wall in creating the mechanism of mechanosignaling, as well as the role of the onset of molecular signaling cascades in the pathology of varicose veins. 相似文献
15.
Endothelial cells live in a dynamic environment where they are constantly exposed to external hemodynamic forces and generate cytoskeletal-based endogenous forces. These exogenous and endogenous forces are critical regulators of endothelial cell health and blood vessel maintenance at all generations of the vascular system, from large arteries to capillary beds. The first part of this review highlights the role of the primary exogenous hemodynamic forces of shear, cyclic strain, and pressure forces in mediating endothelial cell response. We then discuss the emergent role of the mechanical properties of the extracellular matrix and of cellular endogenous force generation on endothelial cell function, implicating substrate stiffness and cellular traction stresses as important mediators of endothelial cell health. The intersection of exogenous and endogenous forces on endothelial cell function is discussed, suggesting some of the many remaining questions in the field of endothelial mechanobiology. 相似文献
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17.
Xian-Ming Wu Ning Zhang Jiang-Shan Li Zhi-Hong Yang Xiao-Lou Huang Xiao-Fang Yang 《Purinergic signalling》2023,19(1):265
Atherosclerosis is the main pathological basis of cardiovascular disease and involves damage to vascular endothelial cells (ECs) that results in endothelial dysfunction (ED). The vascular endothelium is the key to maintaining blood vessel health and homeostasis. ED is a complex pathological process involving inflammation, shear stress, vascular tone, adhesion of leukocytes to ECs, and platelet aggregation. The activation of P2X4, P2X7, and P2Y2 receptors regulates vascular tone in response to shear stress, while activation of the A2A, P2X4, P2X7, P2Y1, P2Y2, P2Y6, and P2Y12 receptors promotes the secretion of inflammatory cytokines. Finally, P2X1, P2Y1, and P2Y12 receptor activation regulates platelet activity. These purinergic receptors mediate ED and participate in atherosclerosis. In short, P2X4, P2X7, P2Y1, and P2Y12 receptors are potential therapeutic targets for atherosclerosis. 相似文献
18.
《Cell Adhesion & Migration》2013,7(5):517-524
Endothelial cells lining blood vessels are exposed to various hemodynamic forces associated with blood flow. These include fluid shear, the tangential force derived from the friction of blood flowing across the luminal cell surface, tensile stress due to deformation of the vessel wall by transvascular flow, and normal stress caused by the hydrodynamic pressure differential across the vessel wall. While it is well known that these fluid forces induce changes in endothelial morphology, cytoskeletal remodeling, and altered gene expression, the effect of flow on endothelial organization within the context of the tumor microenvironment is largely unknown. Using a previously established microfluidic tumor vascular model, the objective of this study was to investigate the effect of normal (4 dyn/cm2), low (1 dyn/cm2), and high (10 dyn/cm2) microvascular wall shear stress (WSS) on tumor-endothelial paracrine signaling associated with angiogenesis. It is hypothesized that high WSS will alter the endothelial phenotype such that vascular permeability and tumor-expressed angiogenic factors are reduced. Results demonstrate that endothelial permeability decreases as a function of increasing WSS, while co-culture with tumor cells increases permeability relative to mono-cultures. This response is likely due to shear stress-mediated endothelial cell alignment and tumor-VEGF-induced permeability. In addition, gene expression analysis revealed that high WSS (10 dyn/cm2) significantly down-regulates tumor-expressed MMP9, HIF1, VEGFA, ANG1, and ANG2, all of which are important factors implicated in tumor angiogenesis. This result was not observed in tumor mono-cultures or static conditioned media experiments, suggesting a flow-mediated paracrine signaling mechanism exists with surrounding tumor cells that elicits a change in expression of angiogenic factors. Findings from this work have significant implications regarding low blood velocities commonly seen in the tumor vasculature, suggesting high shear stress-regulation of angiogenic activity is lacking in many vessels, thereby driving tumor angiogenesis. 相似文献
19.
The identification of collateral artery growth (arteriogenesis) as the only mechanism to compensate for the loss of an occluded
artery forced us to define the mechanisms responsible for this type of vessel growth. To achieve this, a variety of coronary
as well as peripheral models of arteriogenesis have been developed. Based on these studies it is obvious that arteriogenesis
obeys different mechanisms than angiogenesis, the sprouting of capillaries. Upon occlusion of an artery, the blood flow is
redirected into preexisting arteriolar anastomoses that experience increased mechanical forces such as shear stress and circum
ferential wall stress. The endothelium of the arteriolar connections is then activated, resulting in an increased release
of monocyte-attracting proteins as well as an upregulation of adhesion molecules. Upon adherence and extravasation, monocytes
promote arteriogenesis by supplying growth factors and cytokines that bind to receptors that are expressed on vascular cells
within a limited time frame. Animal studies evidenced that factors, such as monocyte chemoattractant protein-1, granulocyte-monocyte
colony-stimulating factor, or transforming growth factor-β1, that either attract or prolong the lifetime of monocytes efficiently enhance collateral artery growth, an effect that was
seen only to a minor degree after application of a single growth factor. Bone marrow-derived stems cells and endothelial progenitor
cells do not incorporate in growing arteries but, rather, function as supporting cells. Complete elucidation of the mechanisms
of arteriogenesis may lead to efficacious therapies counteracting the devastating consequences of vascular occlusive diseases. 相似文献
20.
Select de novo Gene and Protein Expression During Renal Epithelial Cell Culture in Rotating Wall Vessels is Shear Stress Dependent 总被引:4,自引:0,他引:4
Kaysen JH Campbell WC Majewski RR Goda FO Navar GL Lewis FC Goodwin TJ Hammond TG 《The Journal of membrane biology》1999,168(1):77-89
The rotating wall vessel has gained popularity as a clinical cell culture tool to produce hormonal implants. It is desirable
to understand the mechanisms by which the rotating wall vessel induces genetic changes, if we are to prolong the useful life
of implants. During rotating wall vessel culture gravity is balanced by equal and opposite hydrodynamic forces including shear
stress. The current study provides the first evidence that shear stress response elements, which modulate gene expression
in endothelial cells, are also active in epithelial cells. Rotating wall culture of renal cells changes expression of select
gene products including the giant glycoprotein scavenger receptors cubulin and megalin, the structural microvillar protein
villin, and classic shear stress response genes ICAM, VCAM and MnSOD. Using a putative endothelial cell shear stress response
element binding site as a decoy, we demonstrate the role of this sequence in the regulation of selected genes in epithelial
cells. However, many of the changes observed in the rotating wall vessel are independent of this response element. It remains
to define other genetic response elements modulated during rotating wall vessel culture, including the role of hemodynamics
characterized by 3-dimensionality, low shear and turbulence, and cospatial relation of dissimilar cell types.
Received: 30 June 1998/Revised: 30 November 1998 相似文献