scholarly journals Mechanotransduction in the Cardiovascular System: From Developmental Origins to Homeostasis and Pathology

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1607 ◽  
Author(s):  
Gloria Garoffolo ◽  
Maurizio Pesce
Keyword(s):  
Cardiovascular System ◽  
Mechanical Forces ◽  
Mechanical Stimuli ◽  
Flow Shear ◽  
Surrounding Matrix ◽  
Cellular Mechanotransduction ◽  
Flow Shear Stress ◽  
Sense And Respond ◽  
Metabolic Dysfunctions

With the term ‘mechanotransduction’, it is intended the ability of cells to sense and respond to mechanical forces by activating intracellular signal transduction pathways and the relative phenotypic adaptation. While a known role of mechanical stimuli has been acknowledged for developmental biology processes and morphogenesis in various organs, the response of cells to mechanical cues is now also emerging as a major pathophysiology determinant. Cells of the cardiovascular system are typically exposed to a variety of mechanical stimuli ranging from compression to strain and flow (shear) stress. In addition, these cells can also translate subtle changes in biophysical characteristics of the surrounding matrix, such as the stiffness, into intracellular activation cascades with consequent evolution toward pro-inflammatory/pro-fibrotic phenotypes. Since cellular mechanotransduction has a potential readout on long-lasting modifications of the chromatin, exposure of the cells to mechanically altered environments may have similar persisting consequences to those of metabolic dysfunctions or chronic inflammation. In the present review, we highlight the roles of mechanical forces on the control of cardiovascular formation during embryogenesis, and in the development and pathogenesis of the cardiovascular system.

scholarly journals Piezo Channels: Awesome Mechanosensitive Structures in Cellular Mechanotransduction and Their Role in Bone

2021 ◽  
Vol 22 (12) ◽  
pp. 6429
Author(s):  
Xia Xu ◽  
Shuyu Liu ◽  
Hua Liu ◽  
Kang Ru ◽  
Yunxian Jia ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Cells ◽  
Current Knowledge ◽  
Bone Diseases ◽  
Mechanical Forces ◽  
Mechanical Stimuli ◽  
Cellular Mechanotransduction ◽  
Piezo Channels ◽  
And Function

Piezo channels are mechanosensitive ion channels located in the cell membrane and function as key cellular mechanotransducers for converting mechanical stimuli into electrochemical signals. Emerged as key molecular detectors of mechanical forces, Piezo channels’ functions in bone have attracted more and more attention. Here, we summarize the current knowledge of Piezo channels and review the research advances of Piezo channels’ function in bone by highlighting Piezo1′s role in bone cells, including osteocyte, bone marrow mesenchymal stem cell (BM-MSC), osteoblast, osteoclast, and chondrocyte. Moreover, the role of Piezo channels in bone diseases is summarized.

Key role of α1β1-integrin in the activation of PI3-kinase-Akt by flow (shear stress) in resistance arteries

2008 ◽  
Vol 294 (4) ◽  
pp. H1906-H1913 ◽  
Author(s):  
Laurent Loufrani ◽  
Kevin Retailleau ◽  
Arnaud Bocquet ◽  
Odile Dumont ◽  
Kerstin Danker ◽  
...  
Keyword(s):  
Shear Stress ◽  
Metabolic Diseases ◽  
Inhibitory Effect ◽  
Pi3 Kinase ◽  
Resistance Arteries ◽  
Flow Shear ◽  
Phosphorylated Akt ◽  
Flow Shear Stress ◽  
Stress Dependent

Resistance arteries are the site of the earliest manifestations of many cardiovascular and metabolic diseases. Flow (shear stress) is the main physiological stimulus for the endothelium through the activation of vasodilatory pathways generating flow-mediated dilation (FMD). The role of FMD in local blood flow control and angiogenesis is well established, and alterations in FMD are early markers of cardiovascular disorders. α1-Integrin, which has a role in angiogenesis, could be involved in FMD. FMD was studied in mesenteric resistance arteries (MRA) isolated in arteriographs. The role of α1-integrins in FMD was tested with selective antibodies and mice lacking the gene encoding for α1-integrins. Both anti-α1blocking antibodies and genetic deficiency in α1-integrin in mice (α1−/−) inhibited FMD without affecting receptor-mediated (acetylcholine) endothelium-dependent dilation or endothelium-independent dilation (sodium nitroprusside). Similarly, vasoconstrictor tone (myogenic tone and phenylephrine-induced contraction) was not affected. In MRA phosphorylated Akt and phosphatidylinositol 3-kinase (PI3-kinase) were significantly lower in α1−/−mice than in α1+/+mice, although total Akt and endothelial nitric oxide synthase (eNOS) were not affected. Pharmacological blockade of PI3-kinase-Akt pathway with LY-294002 inhibited FMD. This inhibitory effect of LY-294002 was significantly lower in α1−/−mice than in α1+/+mice. Thus α1-integrin has a key role in flow (shear stress)-dependent vasodilation in resistance arteries by transmitting the signal to eNOS through activation of PI3-kinase and Akt. Because of the central role of flow (shear stress) activation of the endothelium in vascular disorders, this finding opens new perspectives in the pathophysiology of the microcirculation and provides new therapeutic targets.

A test of the role of flow-dependent dilation in arteriolar responses to occlusion

1997 ◽  
Vol 272 (2) ◽  
pp. H714-H721 ◽  
Author(s):  
E. D. McGahren ◽  
K. A. Dora ◽  
D. N. Damon ◽  
B. R. Duling
Keyword(s):  
Shear Stress ◽  
Baseline Level ◽  
Cheek Pouch ◽  
Hamster Cheek Pouch ◽  
Flow Shear ◽  
Flow Through ◽  
Flow Shear Stress ◽  
Arteriolar Diameter

At an arteriolar bifurcation, occlusion of one of the branch arterioles has been reported to result in an increase in flow, shear stress, and vasodilation in the opposite unoccluded branch. This dilator response in the unoccluded branch, often referred to as the "parallel occlusion response," has been cited as evidence that flow-dependent dilation is a primary regulator of arteriolar diameter in the microcirculation. It has not been previously noted that, during this maneuver, flow through the feed arteriole would be expected to decrease and logically should cause that vessel to constrict. We tested this prediction in vivo by measuring red blood cell (RBC) velocity and diameter changes in response to arteriolar occlusion in the microcirculatory beds of three preparations: the hamster cheek pouch, the hamster cremaster, and the rat cremaster. In all preparations, a vasodilation was observed in the feed arteriole, despite a decrease in both flow and calculated wall shear stress through this vessel. Unexpectedly, we found that dilation occurred in the unoccluded branch arterioles even in those cases in which RBC velocity and shear stress did not increase in the unoccluded branch arterioles. All values returned to the baseline level after the removal of occlusion. The magnitude of the dilation of the feed and branch arterioles varied between species and tissues, but feed and branch arterioles within a given preparation always responded in a similar way to each other. We conclude from our experiments that mechanisms other than flow-dependent dilation are involved in the vasodilation observed in the microcirculation during occlusion of an arteriolar branch.

Tissue Engineered Tumor Microvessels to Study the Role of Flow Shear Stress on Endothelial Barrier Function

2013 ◽  
Author(s):  
Cara F. Buchanan ◽  
Elizabeth Voigt ◽  
Pavlos P. Vlachos ◽  
Marissa Nichole Rylander
Keyword(s):  
Shear Stress ◽  
Growth Factors ◽  
Vascular Function ◽  
Fluid Pressure ◽  
Compressive Force ◽  
Lymphatic Drainage ◽  
Angiogenic Growth Factors ◽  
Flow Shear ◽  
Flow Shear Stress

As solid tumors develop, a variety of physical stresses arise including growth induced compressive force, matrix stiffening due to desmoplasia, and increased interstitial fluid pressure and altered flow patterns due to leaky vasculature and poor lymphatic drainage [1]. These microenvironmental stresses likely contribute to the abnormal cell behavior that drives tumor progression, and have become an increasingly significant area of cancer research. Of particular importance, is the role of flow shear stress on tumor-endothelial signaling, vascular function, and angiogenesis. Compared to normal vasculature, blood vessels in tumors are poorly functional due to dysregulated expression of angiogenic growth factors, such as vascular endothelial growth factor (VEGF) or the angiopoietins. Also, because of the abnormal vessel structure, blood velocities can be an order of magnitude lower than that of normal microvessels. Recently published work utilizing intravital microscopy to measure blood velocities in mouse mammary fat pad tumors, demonstrated for the first time that shear rate gradients in tumors may help guide branching and growth of new vessels [2]. However, much still remains unknown about how shear stress regulates endothelial organization, permeability, or expression of growth factors within the context of the tumor microenvironment.

scholarly journals The role of mechanical forces in the planar-to-bulk transition in growing Escherichia coli microcolonies

2014 ◽  
Vol 11 (97) ◽  
pp. 20140400 ◽  
Author(s):  
Matthew A. A. Grant ◽  
Bartłomiej Wacław ◽  
Rosalind J. Allen ◽  
Pietro Cicuta
Keyword(s):  
Escherichia Coli ◽  
Colony Size ◽  
Three Dimensional ◽  
Phenomenological Theory ◽  
Mechanical Forces ◽  
Bacterial Cells ◽  
Experimental Conditions ◽  
Surrounding Matrix ◽  
Dimensional Growth

Mechanical forces are obviously important in the assembly of three-dimensional multicellular structures, but their detailed role is often unclear. We have used growing microcolonies of the bacterium Escherichia coli to investigate the role of mechanical forces in the transition from two-dimensional growth (on the interface between a hard surface and a soft agarose pad) to three-dimensional growth (invasion of the agarose). We measure the position within the colony where the invasion transition happens, the cell density within the colony and the colony size at the transition as functions of the concentration of the agarose. We use a phenomenological theory, combined with individual-based computer simulations, to show how mechanical forces acting between the bacterial cells, and between the bacteria and the surrounding matrix, lead to the complex phenomena observed in our experiments—in particular the observation that agarose concentration non-trivially affects the colony size at transition. Matching these approaches leads to a prediction for how the friction between the bacteria and the agarose should vary with agarose concentration. Our experimental conditions mimic numerous clinical and environmental scenarios in which bacteria invade soft matrices, as well as shedding more general light on the transition between two- and three-dimensional growth in multicellular assemblies.

scholarly journals The Mechanobiology of Endothelial-to-Mesenchymal Transition in Cardiovascular Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Shahrin Islam ◽  
Kristina I. Boström ◽  
Dino Di Carlo ◽  
Craig A. Simmons ◽  
Yin Tintut ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cardiovascular System ◽  
Therapeutic Interventions ◽  
Cell Phenotype ◽  
Cardiovascular Development ◽  
Mechanical Stimuli ◽  
Mesenchymal Transition ◽  
Pulsatile Pressure ◽  
Endothelial To Mesenchymal Transition

Endothelial cells (ECs) lining the cardiovascular system are subjected to a highly dynamic microenvironment resulting from pulsatile pressure and circulating blood flow. Endothelial cells are remarkably sensitive to these forces, which are transduced to activate signaling pathways to maintain endothelial homeostasis and respond to changes in the environment. Aberrations in these biomechanical stresses, however, can trigger changes in endothelial cell phenotype and function. One process involved in this cellular plasticity is endothelial-to-mesenchymal transition (EndMT). As a result of EndMT, ECs lose cell-cell adhesion, alter their cytoskeletal organization, and gain increased migratory and invasive capabilities. EndMT has long been known to occur during cardiovascular development, but there is now a growing body of evidence also implicating it in many cardiovascular diseases (CVD), often associated with alterations in the cellular mechanical environment. In this review, we highlight the emerging role of shear stress, cyclic strain, matrix stiffness, and composition associated with EndMT in CVD. We first provide an overview of EndMT and context for how ECs sense, transduce, and respond to certain mechanical stimuli. We then describe the biomechanical features of EndMT and the role of mechanically driven EndMT in CVD. Finally, we indicate areas of open investigation to further elucidate the complexity of EndMT in the cardiovascular system. Understanding the mechanistic underpinnings of the mechanobiology of EndMT in CVD can provide insight into new opportunities for identification of novel diagnostic markers and therapeutic interventions.

scholarly journals Vascular dysfunction and pathology: focus on mechanical forces

2021 ◽  
Author(s):  
Gloria Garoffolo ◽  
Maurizio Pesce
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Cardiovascular System ◽  
Vascular Dysfunction ◽  
Force Distribution ◽  
Mechanical Forces ◽  
Biophysical Properties ◽  
Epigenetic Programming ◽  
New Concepts

The role of mechanical forces is emerging as a new player in pathophysiologic programming of the cardiovascular system. The ability of the cells to ‘sense’ mechanical forces does not relate only to perception of movement or flow, as intended traditionally, but also to the biophysical properties of the extracellular matrix, the geometry of the tissues and the force distribution inside them. This is also supported by the finding that cells can actively translate mechanical cues into discrete gene expression and epigenetic programming. In the present review we will contextualize these new concepts in the vascular pathologic programming.

Flow shear stress controls the initiation of neovascularization via heparan sulfate proteoglycans within a biomimetic microfluidic model

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Ping Zhao ◽  
Xiao Liu ◽  
Xing Zhang ◽  
Li Wang ◽  
Haoran Su ◽  
...  
Keyword(s):  
Shear Stress ◽  
Heparan Sulfate ◽  
Heparan Sulfate Proteoglycans ◽  
Flow Shear ◽  
Flow Shear Stress

The role of shear stress was investigated in a biomimetic microfluidic model that recapitulates the initial physiological microenvironment of neovascularization.

scholarly journals I022 Role of heme oxygenase-1 in high blood flow (shear stress)-induced remodeling of rat resistance arteries

2009 ◽  
Vol 102 ◽  
pp. S94
Author(s):  
M.-L. Freidja ◽  
E. Vessieres ◽  
B. Toutain ◽  
L. Loufrani ◽  
S. Faure ◽  
...  
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Resistance Arteries ◽  
Flow Shear ◽  
Flow Shear Stress
Sign in / Sign up

Export Citation Format

Share Document