scholarly journals Mechanical factors direct mouse aortic remodelling during early maturation

2015 ◽  
Vol 12 (104) ◽  
pp. 20141350 ◽  
Author(s):  
Victoria P. Le ◽  
Jeffrey K. Cheng ◽  
Jungsil Kim ◽  
Marius C. Staiculescu ◽  
Shawn W. Ficker ◽  
...  
Keyword(s):  
Arterial Wall ◽  
Arterial Compliance ◽  
Collagen Fibre ◽  
Constitutive Modelling ◽  
Elastic Fibre ◽  
Wild Type ◽  
Elastic Fibres ◽  
Early Maturation ◽  
Arterial Wall Mechanics ◽  
Mechanical Factors

Numerous diseases have been linked to genetic mutations that lead to reduced amounts or disorganization of arterial elastic fibres. Previous work has shown that mice with reduced amounts of elastin ( Eln+/− ) are able to live a normal lifespan through cardiovascular adaptations, including changes in haemodynamic stresses, arterial geometry and arterial wall mechanics. It is not known if the timeline and presence of these adaptations are consistent in other mouse models of elastic fibre disease, such as those caused by the absence of fibulin-5 expression ( Fbln5−/− ). Adult Fbln5−/− mice have disorganized elastic fibres, decreased arterial compliance and high blood pressure. We examined mechanical behaviour of the aorta in Fbln5−/− mice through early maturation when the elastic fibres are being assembled. We found that the physiologic circumferential stretch, stress and modulus of Fbln5−/− aorta are maintained near wild-type levels. Constitutive modelling suggests that elastin contributions to the total stress are decreased, whereas collagen contributions are increased. Understanding how collagen fibre structure and mechanics compensate for defective elastic fibres to meet the mechanical requirements of the maturing aorta may help to better understand arterial remodelling in human elastinopathies.

Abstract 101: Dipeptidylpeptidase-iv Inhibition Using MK626 Attenuates BAPB/AT2 Induced Murine Aneurysm

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
John S Byrne ◽  
Emily Chen ◽  
Mansoor Husain ◽  
Maral Ouzounian ◽  
Clint Robbins ◽  
...  
Keyword(s):  
Cross Sections ◽  
Elastic Fibre ◽  
Wild Type ◽  
Aneurysmal Dilatation ◽  
Descending Aorta ◽  
Dipeptidylpeptidase Iv ◽  
Matrix Deposition ◽  
Suprarenal Aorta ◽  
Recent Addition ◽  
Glucagon Like Peptide 1

The dearth of effective treatments to diminish aneurysm progression is a recognized clinical challenge. Modulation of the glucagon-like peptide-1 (GLP-1) pathway is a recent addition to anti-diabetic management regimes, and has pleiotropic effects to inhibit arterial wall macrophage infiltration, a key pathological event in aneurysmal disease. We therefore hypothesized that inhibition of endogenous breakdown of GLP-1, using the dipeptidylpeptidase-IV inhibitor MK626, would attenuate BAPN/AT2 induced murine aneurysm. Eight-week-old C57/Bl6 mice received two weeks of oral beta-aminopropriononitrile (BAPN) and four weeks of angiotensin-2 (AT2) via mini-osmotic pump. MK626 3mg/kg in methylcellulose vehicle was administered daily and compared to control methylcellulose vehicle. At four weeks, whole aortas were dissected and photomicrographed. Cross sections of aorta were stained using H&E and EVG. Compared to wild-type, BAPN/AT2 caused dilatation of the aorta from the ascending to the suprarenal segment (p<0.002) with infrarenal sparing (p=0.77). Focal aneurysmal dilatation reproducibly occurred in the suprarenal aorta (wild-type diameter 0.93±0.03mm, n=8; BAPN/AT2 diameter 2.26±0.12, n=8; p<0.0001). Treatment with MK626 attenuated dilatation of the descending aorta compared to controls (BAPN/AT2 control 1.26±0.05mm, n=8; MK626 1.07±0.05mm, n=10; p=0.03). The focal suprarenal aneurysmal dilatation was significantly reduced by treatment with MK626 (BAPN AT2 control 2.26±0.34mm, n=8; MK626 1.66±0.32mm, n=10; p=0.0001). BAPN/AT2 induced aortic aneurysm was associated with excess matrix deposition, increased medial thickness, and elastic fibre fragmentation. Modulation of the GLP pathway using the dipeptidylpeptidase-IV inhibitor MK626 attenuates aneurysm in a BAPN/AT2 induced murine model.

A computational model for collagen fibre remodelling in the arterial wall

2004 ◽  
Vol 226 (1) ◽  
pp. 53-64 ◽  
Author(s):  
N.J.B. Driessen ◽  
W. Wilson ◽  
C.V.C. Bouten ◽  
F.P.T. Baaijens
Keyword(s):  
Computational Model ◽  
Arterial Wall ◽  
Collagen Fibre ◽  
Fibre Remodelling

The Mechanical Properties of Porcine Coronary Arteries Determined With a Mixed Experimental-Numerical Approach

2008 ◽  
Author(s):  
Arjen van der Horst ◽  
Chantal N. van den Broek ◽  
Marcel C. M. Rutten ◽  
Frans N. van de Vosse
Keyword(s):  
United States ◽  
Mechanical Properties ◽  
Coronary Arteries ◽  
Arterial Wall ◽  
Coronary Circulation ◽  
Mechanical Characterization ◽  
Numerical Approach ◽  
The United States ◽  
Mechanical Factors

Mechanical characterization of the coronary arterial wall is important for several reasons. Mechanical factors play an important role in the development of atherosclerosis [1]. Atherosclerotic coronary arteries may be treated mechanically with interventions like PTCA and stent implantation, 1265000 PTCA procedures were performed in the United States in 2005 [2]. Furthermore, knowledge of the mechanical properties of the arterial wall is important for modeling of the coronary circulation and explaining its hemodynamics.

scholarly journals Clinical and vascular responses to propranolol and candesartan in migraine patients: A randomized controlled clinical trial

2020 ◽  
Vol 3 ◽  
pp. 251581632094649
Author(s):  
Aros Dlawer Barzenje ◽  
Knut Gjesdal ◽  
Bendik Slagsvold Winsvold ◽  
Milada Cvancarova Småstuen ◽  
Lars Jacob Stovner ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Arterial Wall ◽  
Clinical Effect ◽  
Arterial Compliance ◽  
Drug Effects ◽  
Controlled Clinical Trial ◽  
Noninvasive Blood Pressure ◽  
Randomized Controlled ◽  
Prophylactic Drugs ◽  
Wall Stiffness

Background: Both propranolol and candesartan are prophylactic drugs for migraine, but with unknown mechanisms of action. The objectives of the present study were to investigate these drugs’ effects on arterial wall dynamics and the potential relation between their vascular and clinical effect. Methods: The study was based on data from a previously published randomized, placebo-controlled, triple-blinded, double crossover clinical trial comparing the prophylactic effects of candesartan and propranolol in 72 patients. Finapres noninvasive blood pressure curves were analyzed. On the descending limb of the pulse curve, a notch is produced by pulse wave reflection, and its relative height compared to the top of the curve (the notch ratio) was used as a marker of arterial wall stiffness. Results: Candesartan decreased the notch ratio from baseline ( p = 0.005), reflecting more compliant arteries and vasodilation, whereas propranolol increased the notch ratio ( p = 0.005), reflecting less compliant arteries and vasoconstriction. There was no difference in baseline notch ratio between clinical responders and nonresponders. Conclusion: The drugs are both efficient prophylactic medications, yet they have opposite effects on arterial wall dynamics. This suggests that drug effects other than those on arterial compliance must be responsible for their prophylactic effect in migraine.

scholarly journals Constitutive modelling of arteries considering fibre recruitment and three-dimensional fibre distribution

2015 ◽  
Vol 12 (105) ◽  
pp. 20150111 ◽  
Author(s):  
Hannah Weisbecker ◽  
Michael J. Unterberger ◽  
Gerhard A. Holzapfel
Keyword(s):  
Experimental Data ◽  
Matrix Material ◽  
Three Dimensional ◽  
Collagen Fibre ◽  
Multiscale Model ◽  
Orientation Distribution ◽  
Constitutive Modelling ◽  
Collagen Fibres ◽  
Proposed Model ◽  
The Matrix

Structurally motivated material models may provide increased insights into the underlying mechanics and physics of arteries under physiological loading conditions. We propose a multiscale model for arterial tissue capturing three different scales (i) a single collagen fibre; (ii) bundle of collagen fibres; and (iii) collagen network within the tissue. The waviness of collagen fibres is introduced by a probability density function for the recruitment stretch at which the fibre starts to bear load. The three-dimensional distribution of the collagen fibres is described by an orientation distribution function using the bivariate von Mises distribution, and fitted to experimental data. The strain energy for the tissue is decomposed additively into a part related to the matrix material and a part for the collagen fibres. Volume fractions account for the matrix/fibre constituents. The proposed model only uses two parameters namely a shear modulus of the matrix material and a (stiffness) parameter related to a single collagen fibre. A fit of the multiscale model to representative experimental data obtained from the individual layers of a human thoracic aorta shows that the proposed model is able to adequately capture the nonlinear and anisotropic behaviour of the aortic layers.

scholarly journals PKCε Increases Extracellular Elastin and Fibulin-5/DANCE in Dermal Fibroblasts

2018 ◽  
Vol 46 (1) ◽  
pp. 291-302
Author(s):  
Tomoyuki Nishizaki
Keyword(s):  
Extracellular Space ◽  
Treatment Time ◽  
Elastic Fibre ◽  
Dermal Fibroblasts ◽  
Protein Synthesis Inhibitor ◽  
Dependent Manner ◽  
Human Dermal Fibroblasts ◽  
Elastic Fibres ◽  
Cultured Fibroblasts ◽  
Extracellular Matrix Components

Background/Aims: In the earlier study, the selective PKCε activator DCP-LA increased elastic fibres in the dermis of HR-1 hairless mice. As a process of elastic fibre formation, tropoelastin, an elastin monomer, is secreted into the extracellular space. Secreted tropoelastin is delivered to the microfibrils by fibulin-5/developmental arteries and neural crest epidermal growth factor-like (DANCE) and undergoes self-association. Then, tropoelastin assembles around the microfibrils, growing into elastin and elastic fibres by lysyl oxidase (LOX)- or LOX-like (LOXL)-mediated cross-linking. The present study was conducted to understand the mechanism underlying DCP-LA-induced increase in elastin/elastic fibre. Methods: Western blotting, immunocytochemistory, and real-time reverse transcription-polymerase chain reaction (RT-PCR) were carried out in cultured human dermal fibroblasts. PKCε, mammalian target of rapamycin complex (mTOR), and p70 S6 kinase (S6K) were knocked-down by transfecting each siRNA. Results: DCP-LA increased elastin and fibulin-5/DANCE in a treatment time (6-24 h)- and a bell-shaped concentration (1 nM-1 µM)-dependent manner in the culture medium of human dermal fibroblasts. DCP-LA markedly increased elastic fibres in the extracellular space of cultured fibroblasts. DCP-LA-induced increase in extracellular elastin and fibulin-5/DANCE was abolished by a PKC inhibitor or knocking-down PKCε. DCP-LA did not affect expression of mRNAs for tropoelastin and fiblin-5/DANCE in cultured fibroblasts. DCP-LA-induced increase in extracellular elastin and fibulin-5/DANCE was not inhibited by the protein synthesis inhibitor cycloheximide or by knocking-down mTOR and S6K. DCP-LA never increased extracellular elastin in the presence of elastase, that breaks down elastin. An inhibitor of matrix metalloproteinase 9, that degrades multiple extracellular matrix components including elastin, had no effect on the basal levels and the DCP-LA-induced increase levels of extracellular elastin. Conclusion: The results of the present study indicate that PKCε, activated by DCP-LA, increases elastin and fibulin-5/DANCE in the extracellular space of cultured fibroblasts by the mechanism independent of transcriptional and translational modulation or inhibition of elastolysis.

Passive Biaxial Mechanical Response of Aged Human Iliac Arteries

2003 ◽  
Vol 125 (3) ◽  
pp. 395-406 ◽  
Author(s):  
Christian A. J. Schulze-Bauer ◽  
Christian Mo¨rth ◽  
Gerhard A. Holzapfel
Keyword(s):  
Experimental Data ◽  
Deformation Behavior ◽  
Arterial Wall ◽  
Constitutive Models ◽  
Intraluminal Pressure ◽  
Clear Correlation ◽  
Outer Diameter ◽  
Iliac Arteries ◽  
Arterial Wall Mechanics

Inflation and extension tests of arteries are essential for the understanding of arterial wall mechanics. Data for such tests of human arteries are rare. At autopsy we harvested 10 non-diseased external iliac arteries of aged subjects (52–87 yrs). Structural homogeneity was ensured by means of ultrasound imaging, and anamneses of patients were recorded. We measured the axial in situ stretches, load-free geometries and opening angles. Passive biaxial mechanical responses of preconditioned cylindrical specimens were studied in 37°C calcium-free Tyrode solution under quasistatic loading conditions. Specimens were subjected to pressure cycles varying from 0 to 33.3kPa (250mmHg) at nine fixed axial loads, varying from 0 to 9.90N. For the description of the load-deformation behavior we employed five “two-dimensional” orthotropic strain-energy functions frequently used in arterial wall mechanics. The associated constitutive models were compared in regard to their ability of representing the experimental data. Histology showed that the arteries were of the muscular type. In contrast to animal arteries they exhibited intimal layers of considerable thickness. The average ratio of wall thickness to outer diameter was 7.7, which is much less than observed for common animal arteries. We found a clear correlation between age and the axial in situ stretch λis(r=−0.72,P=0.03), and between age and distensibility of specimens, i.e. aged specimens are less distensible. Axial in situ stretches were clearly smaller (1.07±0.09,mean±SD) than in animal arteries. For one specimen λis was even smaller than 1.0, i.e. the vessel elongated axially upon excision. The nonlinear and anisotropic load-deformation behavior showed small hystereses. For the majority of specimens we observed axial stretches smaller than 1.3 and circumferential stretches smaller than 1.1 for the investigated loading range. Data from in situ inflation tests showed a significant increase of the axial stretch with intraluminal pressure. Thus, for this type of artery the axial in situ stretch of a non-pressurized vessel is not representative of the axial in vivo stretch. None of the constitutive models were able to represent the deformation behavior of the entire loading range. For the physiological loading range, however, some of the models achieved good agreement with the experimental data.

Mechanics and Modeling of Postnatal Arterial Development in Wild-Type and Elastin-Insufficient Mice

2011 ◽  
Author(s):  
Jeffrey K. Cheng ◽  
Victoria Le ◽  
Robert P. Mecham ◽  
Jessica E. Wagenseil
Keyword(s):  
Mechanical Properties ◽  
Feedback Loop ◽  
Arterial Wall ◽  
Time Pressure ◽  
Wild Type ◽  
Collagen Expression ◽  
Ecm Proteins ◽  
Output Increase ◽  
Baseline Levels ◽  
Arterial Development

Large arteries in vertebrates serve as elastic reservoirs that store a portion of the blood volume with systole and discharge it during diastole. This function is made possible by the combination of extracellular matrix (ECM) proteins deposited by the smooth muscle cells (SMCs) in the arterial wall. Elastin and collagen expression in mice is first detectable around embryonic day 14 and peaks around postnatal day (P) 14, returning to baseline levels by P30. During this time, pressure and cardiac output increase significantly before leveling off ∼P30 [1]. Hence, the protein amounts and consequent mechanical properties of the arterial wall change simultaneously with the applied hemodynamic loads in a complicated and unknown feedback loop.

Calcium sensitivity of vasospastic basilar artery after experimental subarachnoid hemorrhage

2006 ◽  
Vol 290 (6) ◽  
pp. H2329-H2336 ◽  
Author(s):  
R. Loch Macdonald ◽  
Zhen-Du Zhang ◽  
Masataka Takahashi ◽  
Elena Nikitina ◽  
J. Young ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Subarachnoid Hemorrhage ◽  
Smooth Muscle Cells ◽  
Arterial Wall ◽  
Arterial Compliance ◽  
Smooth Muscle Actin ◽  
Muscle Cells ◽  
Calcium Sensitivity ◽  
Basilar Arteries

Arteries that develop vasospasm after subarachnoid hemorrhage (SAH) may have altered contractility and compliance. Whether these changes are due to alterations in the smooth muscle cells or the arterial wall extracellular matrix is unknown. This study elucidated the location of such changes and determined the calcium sensitivity of vasospastic arteries. Dogs were placed under general anesthesia and underwent creation of SAH using the double-hemorrhage model. Vasospasm was assessed by angiography performed before and 4, 7, or 21 days after SAH. Basilar arteries were excised from SAH or control dogs ( n = 8–52 arterial rings from 2–9 dogs per measurement) and studied under isometric tension in vitro before and after permeabilization of smooth muscle with α-toxin. Endothelium was removed from all arteries. Vasospastic arteries demonstrated significantly reduced contractility to KCl with a shift in the EC50 toward reduced sensitivity to KCl 4 and 7 days after SAH ( P < 0.05, ANOVA). There was reduced compliance that persisted after permeabilization ( P < 0.05, ANOVA). Calcium sensitivity was decreased during vasospasm 4 and 7 days after SAH, as assessed in permeabilized arteries and in those contracted with BAY K 8644 in the presence of different concentrations of extracellular calcium ( P < 0.05, ANOVA). Depolymerization of actin with cytochalasin D abolished contractions to KCl but failed to alter arterial compliance. In conclusion, it is shown for the first time that calcium sensitivity is decreased during vasospasm after SAH in dogs, suggesting that other mechanisms are involved in maintaining the contraction. Reduced compliance seems to be due to an alteration in the arterial wall extracellullar matrix rather than the smooth muscle cells themselves because it cannot be alleviated by depolymerization of smooth muscle actin.

Arterial Stenting and Overdilation: Does it Change Wall Mechanics in Small-Caliber Arteries?

2002 ◽  
Vol 9 (6) ◽  
pp. 855-862 ◽  
Author(s):  
Hélène Vernhet ◽  
Roland Demaria ◽  
Jean-Marie Juan ◽  
Marie-Claire Oliva-Lauraire ◽  
Jean-Paul Senac ◽  
...  
Keyword(s):  
Arterial Wall ◽  
Rabbit Aorta ◽  
Infrarenal Aorta ◽  
Stent Deployment ◽  
New Zealand White Rabbits ◽  
Group A ◽  
Arterial Wall Mechanics ◽  
Wall Compliance ◽  
Group B ◽  
Arterial Stenting

Purpose: To evaluate changes in arterial wall mechanics induced by stent overdilation in the rabbit aorta. Methods: Twenty New Zealand white rabbits had initial stent deployment (3-mm × 8-mm Multilink) at 10% overdilation. Group A (n=11) had no subsequent balloon expansion of the stent and Group B (n=9) had 30% overdilation of the stent. A noninvasive B-mode ultrasound examination coupled with image processing allowed the measurement of systolic and diastolic diameter and the calculation of diameter compliance (Cd) and distensibility coefficient (DC) as indexes of arterial wall biomechanics. Measurements were performed before stenting in the infrarenal aorta, after initial stenting, and after stent overdilation at 3 locations: upstream, at the stent level, and downstream from the stent. Results: Cd was significantly lower in the stented aorta after initial stenting (p<0.0001) and after stent overdilation (p<0.0001) than before stenting. At the stent level, Cd and DC were significantly lower than downstream (p<0.0001) or upstream (p<0.0001) from the stent after initial stenting, as well as after stent overdilation. Downstream from the stent, Cd and DC were significantly lower after stent overdilation than before stenting (p<0.05). Conclusions: Endovascular stenting of the rabbit aorta produces a significant decrease in arterial wall compliance and distensibility. Stent overdilation is responsible for a slight additional decrease of compliance downstream from the stent.

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