scholarly journals Aortic Stiffness Hysteresis in Isolated Mouse Aortic Segments Is Intensified by Contractile Stimuli, Attenuated by Age, and Reversed by Elastin Degradation

2021 ◽  
Vol 12 ◽  
Author(s):  
Sofie De Moudt ◽  
Arthur Leloup ◽  
Paul Fransen

Aim: Cyclic stretch of vascular tissue at any given pressure reveals greater dimensions during unloading than during loading, which determines the cardiac beat-by-beat hysteresis loop on the pressure-diameter/volume relationship. The present study did not focus on hysteresis during a single stretch cycle but investigated whether aortic stiffness determined during continuous stretch at different pressures also displayed hysteresis phenomena.Methods: Aortic segments from C57Bl6 mice were mounted in the Rodent Oscillatory Set-up for Arterial Compliance (ROTSAC), where they were subjected to high frequency (10 Hz) cyclic stretch at alternating loads equivalent to a constant theoretical pulse pressure of 40 mm Hg. Diastolic and systolic diameter, compliance, and the Peterson elastic modulus (Ep), as a measure of aortic stiffness, was determined starting at cyclic stretch between alternating loads corresponding to 40 and 80 mm Hg, at each gradual load increase equivalent to 20 mm Hg, up to loads equivalent to pressures of 220 and 260 mm Hg (loading direction) and then repeated in the downward direction (unloading direction). This was performed in baseline conditions and following contraction by α1 adrenergic stimulation with phenylephrine or by depolarization with high extracellular K+ in aortas of young (5 months), aged (26 months) mice, and in segments treated with elastase.Results: In baseline conditions, diastolic/systolic diameters and compliance for a pulse pressure of 40 mm Hg were larger at any given pressure upon unloading (decreasing pressure) than loading (increasing pressure) of the aortic segments. The pressure-aortic stiffness (Ep) relationship was similar in the loading and unloading directions, and aortic hysteresis was absent. On the other hand, hysteresis was evident after activation of the VSMCs with the α1 adrenergic agonist phenylephrine and with depolarization by high extracellular K+, especially after inhibition of basal NO release with L-NAME. Aortic stiffness was significantly smaller in the unloading than in the loading direction. In comparison with young mice, old-mouse aortic segments also displayed contraction-dependent aortic hysteresis, but hysteresis was shifted to a lower pressure range. Elastase-treated segments showed higher stiffness upon unloading over nearly the whole pressure range.Conclusions: Mouse aortic segments display pressure- and contraction-dependent diameter, compliance, and stiffness hysteresis phenomena, which are modulated by age and VSMC-extracellular matrix interactions. This may have implications for aortic biomechanics in pathophysiological conditions and aging.

Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Priya Palta ◽  
Jingkai Wei ◽  
Michelle Meyer ◽  
Melinda C Power ◽  
Jennifer A Deal ◽  
...  

Introduction: Small vessel disease is associated with decreased cognitive function, possibly differential by race. Age-related central arterial stiffening increases pulsatility resulting in hypoperfusion, microvascular damage and remodeling in the brain, potentially impairing cognition. We examined if arterial stiffness and pressure amplification are associated with lacunar infarcts and greater volumes of white matter hyperintensities (WMH) in a sample of Caucasian and African American (AA) older adults. Methods: We analyzed a cross-sectional sample of ARIC participants aged 67-90 years (n=1486) from visit 5 (2011-2013), with brain magnetic resonance imaging (MRI). The Omron VP-1000 Plus was used to measure aortic stiffness (carotid-femoral pulse wave velocity [cfPWV]) and pressure amplification measures (pulse pressure amplification [PPA], central pulse pressure [cPP], and estimated central systolic blood pressure [cSBP]). Aortic stiffness and pressure amplification were dichotomized at race-specific 25th percentile cut points. Brain MRI using 3D-1.5T equipment quantified the presence of lacunar infarcts and volumes of WMH following a standardized protocol. Logistic regression, adjusted for age, sex, education, ApoE4, heart rate, smoking and body mass index, was used to quantify the odds of lacunar infarcts in participants with high vs. low cfPWV, cPP, cSBP, and low vs. high PPA. Linear regression models, additionally adjusted for intracranial volume, estimated the difference in log-transformed volumes of WMH among participants with high vs. low cfPWV, cPP, cSBP, and low vs. high PPA. Probability sampling weights for an MRI were included to allow for generalizability to the full visit 5 cohort. Results: Among the 1486 participants with a brain MRI (mean age: 76, 41% male, 26% AA), measures of aortic stiffness and pressure amplification were associated with lacunar infarcts in Caucasians, but not in AAs. Caucasian participants with a high cfPWV had greater odds of lacunar infarcts (Odds Ratio [OR] =2.02, 95% confidence interval [CI]: 1.23, 2.20). Caucasians with high cSBP had higher odds of lacunar infarcts (OR=1.72, 95% CI: 1.10, 2.69). In Caucasians, high cfPWV was associated with a 21% (95% CI: 6, 38) greater volume of WMH as compared to a low cfPWV; high cSBP was associated with a 28% (95% CI: 14, 45) greater volume of WMH compared to a low cSBP. In AAs, high cfPWV was associated with a 32% (95% CI: 7, 62) greater volume of WMH as compared to low cfPWV. Cerebral microvascular imaging markers did not differ quantitatively with measures of PPA and cPP. Conclusions: Central arterial stiffening and pressure amplification are plausible microvascular contributors to cognitive aging, providing new information on modifiable pathways for previously observed associations between cardiovascular disease risk factors and the rates of cognitive decline and dementia among older adults.


1999 ◽  
Vol 276 (2) ◽  
pp. H424-H428 ◽  
Author(s):  
N. Stergiopulos ◽  
P. Segers ◽  
N. Westerhof

We determined total arterial compliance from pressure and flow in the ascending aorta of seven anesthetized dogs using the pulse pressure method (PPM) and the decay time method (DTM). Compliance was determined under control and during occlusion of the aorta at four different locations (iliac, renal, diaphragm, and proximal descending thoracic aorta). Compliance of PPM gave consistently lower values (0.893 ± 0.015) compared with the compliance of DTM (means ± SE; r = 0.989). The lower compliance estimates by the PPM can be attributed to the difference in mean pressures at which compliance is determined (mean pressure, 81.0 ± 3.6 mmHg; mean diastolic pressure, over which the DTM applies, 67.0 ± 3.6 mmHg). Total arterial compliance under control conditions was 0.169 ± 0.007 ml/mmHg. Compliance of the proximal aorta, obtained during occlusion of the proximal descending aorta, was 0.100 ± 0.007 ml/mmHg. Mean aortic pressure was 80.4 ± 3.6 mmHg during control and 102 ± 7.7 mmHg during proximal descending aortic occlusion. From these results and assuming that upper limbs and the head contribute as little as the lower limbs, we conclude that 60% of total arterial compliance resides in the proximal aorta. When we take into account the inverse relationship between pressure and compliance, the contribution of the proximal aorta to the total arterial compliance is even more significant.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Uwe Raaz ◽  
Isabel N Schellinger ◽  
Lars Maegdefessel ◽  
Joshua M Spin ◽  
Gerd Hasenfuss ◽  
...  

Background: Accelerated arterial stiffening is a complication of diabetes mellitus and associated with the development of hypertension. Arterial stiffening results from extensive extracellular matrix remodeling (elastin breakdown, collagen accumulation). MicroRNA miR-29b directly regulates the expression of genes governing fibrosis (such as COL1A1, COL3A1) and elastin breakdown ( MMP2, MMP9 ). However, its impact on aortic stiffness is unclear. Objective: This study was designed to investigate the role of miR-29b as potential mediator of diabetic aortic stiffening. Methods and Results: Serial ex vivo mechanical testing of the thoracic aorta and volume-pressure recording (VPR) based tail-cuff blood pressure measurements revealed that aortic stiffening precedes blood (pulse) pressure elevations in diabetic db/db mice. Vascular stiffening was accompanied by increased elastin fragmentation and collagen deposition (EvG and Picrosirius Red staining). qRT-PCR, in-situ hybridization and immunohistochemistry revealed decreased expression of miR-29b and de-repression of target genes ( Col1A1, COL3A1, MMP2, MMP9 ) in db/db mice compared to controls. Investigating the mechanistic significance of miR-29b for arterial stiffening, forced downregulation of miR-29b (via systemic LNA-miR-29b inhibitor application) results in enhanced elastin fragmentation, increased medial collagen deposition, aortic stiffness and augmented pulse pressure. Conclusions: In conclusion this study identifies miR-29b as a regulator and potential therapeutic target of diabetic aortic stiffening.


2019 ◽  
Vol 33 (1) ◽  
pp. 70-76
Author(s):  
Arturo Figueroa ◽  
Arun Maharaj ◽  
Sarah A Johnson ◽  
Stephen M Fischer ◽  
Bahram H Arjmandi ◽  
...  

Abstract Background Peripheral mean arterial pressure (MAP) responses to muscle metaboreflex activation using postexercise muscle ischemia (PEMI) in type 2 diabetes patients (T2D) are contradictory. Given that aortic pulse pressure (PP) and wave reflections are better indicators of cardiac load than peripheral MAP, we evaluated aortic blood pressure (BP) and wave amplitude during PEMI. METHODS Aortic BP and pressure wave amplitudes were measured at rest and during PEMI following isometric handgrip at 30% maximum voluntary contraction (MVC) in 16 T2D and 15 controls. Resting aortic stiffness (carotid-femoral pulse wave velocity, cfPWV) and fasting blood glucose (FBG) were measured. RESULTS Increases in aortic MAP (Δ26 ± 2 mmHg vs. Δ17 ± 2 mmHg), PP (Δ15 ± 2 mmHg vs. Δ10 ± 1 mmHg), augmentation index (AIx) (Δ8.2 ± 1.0% vs. Δ4.5 ± 1.3%), augmented pressure (AP) (Δ11 ± 1 mmHg vs. Δ5 ± 1 mmHg), forward (Pf) (Δ9 ± 1 mmHg vs. Δ5 ± 1 mmHg), and backward pressure waves (Pb) (Δ10 ± 1 mmHg vs. Δ5 ± 1 mmHg) responses to PEMI were greater in T2D than controls (P < 0.05). Aortic PP, but not MAP, response to PEMI was correlated to Pf (r = 0.63, P < 0.001) and Pb (r = 0.82, P < 0.001) responses and cfPWV (r = 0.37, P < 0.05). CONCLUSIONS Aortic BP and pressure wave responses to muscle metaboreflex activation are exaggerated in T2D. Aortic PP during PEMI was related to increased wave reflection, forward wave amplitude, and aortic stiffness in T2D patients.


Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1620
Author(s):  
Luca Fusaro ◽  
Chiara Gualandi ◽  
Diego Antonioli ◽  
Michelina Soccio ◽  
Anna Liguori ◽  
...  

In the field of artificial prostheses for damaged vessel replacement, polymeric scaffolds showing the right combination of mechanical performance, biocompatibility, and biodegradability are still demanded. In the present work, poly(butylene-co-triethylene trans-1,4-cyclohexanedicarboxylate), a biodegradable random aliphatic copolyester, has been synthesized and electrospun in form of aligned and random fibers properly designed for vascular applications. The obtained materials were analyzed through tensile and dynamic-mechanical tests, the latter performed under conditions simulating the mechanical contraction of vascular tissue. Furthermore, the in vitro biological characterization, in terms of hemocompatibility and cytocompatibility in static and dynamic conditions, was also carried out. The mechanical properties of the investigated scaffolds fit within the range of physiological properties for medium- and small-caliber blood vessels, and the aligned scaffolds displayed a strain-stiffening behavior typical of the blood vessels. Furthermore, all the produced scaffolds showed constant storage and loss moduli in the investigated timeframe (24 h), demonstrating the stability of the scaffolds under the applied conditions of mechanical deformation. The biological characterization highlighted that the mats showed high hemocompatibility and low probability of thrombus formation; finally, the cytocompatibility tests demonstrated that cyclic stretch of electrospun fibers increased endothelial cell activity and proliferation, in particular on aligned scaffolds.


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