Abstract 515: Comparison of Aging and Disturbed Flow Effects on Arterial Wall Biomechanics

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Anastassia Pokutta-Paskaleva ◽  
Rudolph L Gleason ◽  
Luke P Brewster
Keyword(s):  
Shear Stress ◽  
Carotid Artery ◽  
Arterial Stiffness ◽  
Arterial Compliance ◽  
Confocal Imaging ◽  
Disturbed Flow ◽  
Arterial Stiffening ◽  
Post Surgery ◽  
Age Related ◽  
Old Mice

Introduction: Arterial stiffness is an age related disease that doubles ones cardiovascular mortality and functions as an intermediary step in the formation of atherosclerosis. We have recently demonstrated that low and oscillatory wall shear stress, termed disturbed flow (d-flow), leads to arterial stiffness in otherwise normal arteries. Since d-flow has been linked to atherosclerotic plaque formation, our objective is to compare the carotid artery mechanics of 12 week arteries exposed to 4 weeks of d-flow to that of untreated 80 week old s129 mice. We hypothesize that low and oscillatory shear governs the remodeling of the arteries in a way that mimics the effect of arterial stiffening associated with aging. Materials and Methods: We used a partial carotid ligation model in 12-week-old s129 male (n=3) and female (n=3) mice. 4 weeks post surgery we euthanized the animals and performed biaxial extension-inflation biomechanical testing, confocal imaging, histological studies and opening angle studies on the left (partially ligated) carotid artery (LCA) and right (non-ligated) carotid artery (RCA) in order to characterize their biomechanical behavior. The same testing was performed on s129 80-week-old male animals (n=4). Pressure-diameter (P-d) data were collected from cyclic pressurization ramps from 0 to 160 mmHg at constant axial extension levels ranging from 1.3 to 1.9. Compliance was calculated at the in-vivo axial stretch level of 1.7 for both age groups. Intima media thickness was analyzed from H&E stained histological slides. Results were compared with the unpaired, two-tailed t-test and significance was taken at p<0.05. Results and Conclusions: Partial ligation for 4 weeks drastically decreased the compliance of the 12-week-old left carotid in a way that exactly follows the stiffening of the arteries in the 80-week-old mice. The compliance of the non-manipulated right carotid arteries reflected the age related difference in the stiffness of young vs old arteries with statistical difference in the 30 - 90 mmHg range. We have established that low shear stress and oscillatory flow promote the increase in arterial stiffening in the partially ligated young mice in a way that mimics the age-related decrease in arterial compliance in old mice.

Abstract 351: Collagen Alignment Correlates with Differential Biaxial Stiffness in Nonhuman Primate Carotid and Femoral Arteries

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Roy Wang ◽  
Haiyan Li ◽  
William Wan ◽  
Rudy L Gleason ◽  
Luke P Brewster
Keyword(s):  
Carotid Artery ◽  
Arterial Stiffness ◽  
Arterial Compliance ◽  
Matrix Composition ◽  
Biaxial Testing ◽  
Arterial Tree ◽  
Axial Stretch ◽  
Fiber Dispersion ◽  
Femoral Arteries ◽  
Collagen Alignment

Introduction: There are known differences in arterial compliance in different regions of the arterial tree. These differences are thought to be determined by pressure and flow demands of their capacitance artery and their respective tissue bed perfusion requirements, and they may play a role in certain arteries having a greater or lesser prevalence of disease as well as favorable response to intervention. Both the femoral and carotid arteries are susceptible to peripheral arterial disease. Here we define the differences in compliance and analyze the microstructural collagen alignment between these arteries to assess the hypothesis that arterial stiffness, defined as the inverse of compliance, will correlate with collagen alignment. Methods: In-vitro biaxial mechanical tests using a custom system were performed on carotid and femoral arteries excised from non-human primates at necroscopy. Pressure-diameter and force-axial stretch responses were measured, and the arterial compliance ( C , units of %/mmHg x 10 -2 ) at the physiological pressure range to calculate the axial stretch. To characterize the microstructure, planar sections of the arteries were imaged under two-photon confocal microscopy. Three-dimensional, z-stack images were taken at two different locations across the medial thickness for each artery. The images were post-processed using a fast Fourier transform analysis to the quantify fiber angle distributions. Circular descriptive statistics was then used to calculate a fiber dispersion index ( FDI ), where 0≤ FDI ≤1. FDI =0 signifies random fiber dispersion and FDI =1 signifies complete circumferential fiber alignment. T-test statistical analysis was used to compare groups. P<.05 was considered significant. Results: Biaxial testing identified femoral arteries as being more than twice as stiff as the carotid artery (P=.01; Figure). Microstructural fiber analysis demonstrated significantly increased collagen alignment in the femoral compared to carotid artery ( FDI =0.31, n =4 for femoral versus FDI =0.26, n=4 for carotid, p =0.03).Conclusion: Arterial stiffness in the femoral and carotid artery of nonhuman primates correlates with collagen alignment in the vessel media. The absence of a cellular requirement in the observed mechanical behavior of these arteries suggests that not only matrix composition but also alignment contribute to arterial stiffness. Differential arterial responses to procedures, particularly those endovascular in nature, may be expected by these results.

scholarly journals Tetrahydrobiopterin improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women

2012 ◽  
Vol 302 (5) ◽  
pp. H1211-H1218 ◽  
Author(s):  
Kerrie L. Moreau ◽  
Amie Meditz ◽  
Kevin D. Deane ◽  
Wendy M. Kohrt
Keyword(s):  
Nitric Oxide ◽  
Carotid Artery ◽  
Arterial Stiffness ◽  
Postmenopausal Women ◽  
Brachial Artery ◽  
Vascular Function ◽  
Premenopausal Women ◽  
Arterial Stiffening ◽  
Beneficial Effects ◽  
Carotid Artery Compliance

The mechanisms mediating arterial stiffening with aging and menopause are not completely understood. We determined whether administration of tetrahydrobiopterin (BH4), a critical cofactor for endothelial nitric oxide synthase to produce nitric oxide, would increase vascular endothelial-dependent vasodilatory tone and decrease arterial stiffness in estrogen-deficient postmenopausal women. Additionally, we examined whether the beneficial effects of estrogen on vascular function were possibly related to BH4. Arterial stiffness (carotid artery compliance) and endothelial-dependent vasodilation [brachial artery flow-mediated dilation (FMD)] were measured in postmenopausal ( n = 24; 57 ± 1 yr, mean ± SE) and eumenorrheic premenopausal ( n = 9; 33 ± 2 yr) women before and 3 h after the oral administration of BH4. Subsequently, in postmenopausal women, vascular testing (before and after BH4) was repeated following randomization to either 2 days of transdermal estradiol or placebo. Baseline carotid artery compliance and brachial artery FMD were lower in postmenopausal than in premenopausal women ( P < 0.0001). BH4administration increased carotid artery compliance (0.61 ± 0.05 to 0.73 ± 0.04 mm2·mmHg−1·10−1vs. baseline, P < 0.0001) and brachial artery FMD ( P < 0.001) in postmenopausal women but had no effect in premenopausal women ( P = 0.62). Carotid artery compliance (0.59 ± 0.05 to 0.78 ± 0.06 mm2·mmHg−1·10−1, P < 0.001) and FMD increased in postmenopausal women in response to estradiol ( P = 0.02) but were not further improved with the coadministration of BH4, possibly because estrogen increased BH4bioavailability. Carotid artery compliance and FMD increased with BH4in the placebo group ( P = 0.02). Although speculative, these results suggest that reduced vascular BH4may be an important contributor to arterial stiffening in estrogen-deficient postmenopausal women, related in part to reduced endothelial-dependent vasodilatory tone.

Abstract 567: Transcription Factor Runx2 is Induced in Vascular Aging and May Promote Age-related Arterial Stiffness

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Isabel N Schellinger ◽  
Joshua M Spin ◽  
Gerd Hasenfuss ◽  
Philip S Tsao ◽  
Uwe Raaz
Keyword(s):  
Transcription Factor ◽  
Arterial Stiffness ◽  
Ex Vivo ◽  
Vascular Aging ◽  
Arterial Stiffening ◽  
Aortic Smooth Muscle ◽  
Potential Mediator ◽  
Age Related ◽  
Dependent Pathway

Background: Arterial stiffening is a hallmark of vascular aging and may constitute a critical mechanism linking age to increased cardiovascular risk. However, up to now there is no therapy available to efficiently and specifically target age-related arterial stiffening. We recently identified the osteogenic transcription factor Runx2 as an inducer of diabetic arterial stiffness. Objective: The present study investigated the role of Runx2 in the setting of age-related arterial stiffness. Methods and Results: Aortic stiffness – quantified by ex vivo mechanical testing (pressure myography) – was markedly increased in 1-year old male C57Bl/6 mice compared to young (10 week-old) controls. At the same time, Runx2 was aberrantly upregulated in the medial layer of aged aortae, coming along with significant medial fibrosis. Additionally, we detected increased aortic expression of interleukin 6 ( Il6 ) – a key cytokine involved in vascular “inflammaging”. Mechanistically, we found IL-6-induced RUNX2 expression in aortic smooth muscle cells (SMCs) via a NFkB-dependent pathway. Conclusion: In conclusion this study suggests Runx2 as a potential mediator of age-related arterial fibrosis and stiffness warranting further interventional/therapeutic studies.

scholarly journals Effects of endothelin-related gene polymorphisms and aerobic exercise habit on age-related arterial stiffening: a 10-yr longitudinal study

2018 ◽  
Vol 124 (2) ◽  
pp. 312-320 ◽  
Author(s):  
Jun Sugawara ◽  
Tsubasa Tomoto ◽  
Naohiro Noda ◽  
Satoko Matsukura ◽  
Kazuya Tsukagoshi ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Arterial Stiffness ◽  
Aerobic Exercise ◽  
Gene Polymorphisms ◽  
Strong Predictor ◽  
Nucleotide Polymorphisms ◽  
Related Gene ◽  
Arterial Stiffening ◽  
Age Related ◽  
Genetic Risks

Increased arterial stiffness has emerged as a strong predictor of future cardiovascular events and all-cause mortality. The aim of this study was to elucidate influences of endothelin (ET)-related genetic polymorphisms and regular physical activity on age-related arterial stiffening through a 10-yr longitudinal study. A decadal change in brachial-ankle pulse wave velocity (baPWV), an index of arterial stiffness, was evaluated retrospectively among 92 volunteers (63 ± 14 yr, 51 men). The targeted single-nucleotide polymorphisms were ET-A receptor SNP rs5333 (ET-A) and ET-B receptor SNP rs5351 (ET-B). Subjects with either ET-A TC or CC genotypes exhibited significantly greater increases in baPWV (+15.3 ± 11.7 and +16.6 ± 15.7%/dec, respectively) than ET-A TT genotype holders (+9.2 ± 9.0%/dec), whereas subjects with the ET-B GG genotype showed a significantly greater increase in baPWV (+17.7 ± 14.1%/dec) than other ET-B genotype holders (AA: +9.5 ± 10.0%/dec; AG: +11.2 ± 9.6%/dec). The combination of these ET-related genetic risks was associated with a 2.4 times greater decadal increase in baPWV compared with no genetic risk (+8.1 ± 8.4 vs. 19.5 ± 16.0%/dec). In contrast, individuals engaging in >15 METs·h/wk of aerobic exercise showed substantially smaller increases in baPWV (+5.0 ± 9.7%/dec) compared with their physically inactive peers (approximately +13%/dec). These differences remained significant after adjusting for confounding factors, including baseline baPWV and ET-related genotype risk. Our current longitudinal study found that ET-related gene polymorphisms contribute to diverse age-related changes in arterial stiffness, and that regular sufficient aerobic exercise attenuates the age-related arterial stiffening independently of ET-related gene polymorphisms. NEW & NOTEWORTHY This 10-yr longitudinal study suggests that endothelin-related gene polymorphisms contribute to divergent increases in arterial stiffness with advancing age, whereas regular sufficient aerobic exercise attenuates age-related arterial stiffening independently of ET-related gene polymorphisms. This notion partly supports prevailing evidence that regular aerobic exercise contributes to a lower incidence of cardiovascular disease.

Association of plaque echostructure and cardiovascular risk factors with symptomatic carotid artery disease

VASA ◽  
2009 ◽  
Vol 38 (4) ◽  
pp. 357-364 ◽  
Author(s):  
Giannoukas ◽  
Sfyroeras ◽  
Griffin ◽  
Saleptsis ◽  
Antoniou ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Carotid Artery ◽  
Cardiovascular Risk Factors ◽  
Carotid Plaque ◽  
Young Patients ◽  
Symptomatic Disease ◽  
Age Related ◽  
Ica Stenosis

Background: Severity of stenosis remains the main factor for assessing risk of stroke in patients with internal carotid artery (ICA) disease. This study was conducted to investigate the association of plaque echostructure and other established and emerging cardiovascular risk factors with symptomatic ICA disease. Design: Cross-sectional study of consecutive patients with significant (> 50 %) ICA stenosis. Patients and methods: Carotid plaque echostructure, smoking, hypertension, diabetes mellitus, serum lipoprotein (a), homocysteine, vitamin B12, folate, cholesterol to high-density lipoprotein ratio, triglycerides, C-reactive protein, and the Framingham risk score were assessed in 124 consecutive patients (70 asymptomatic; 54 symptomatic) with significant (> 50 %) ICA stenosis. Results: The asymptomatic and symptomatic groups did not differ in terms of gender distribution (p = 0.76) and severity of stenosis (p = 0.62). Echolucent plaques (type 1 and 2) were more predominant in patients with symptomatic disease (p = 0.004, OR = 2.13, 95 % CI = 1.26-3.6). Patients with plaques type 1 were relatively younger than those with type 4 (p = 0.02). None of the other factors assessed had any significant association with symptomatic disease and any type of carotid plaque. Conclusions: Besides the severity of carotid stenosis, the presence of an echolucent plaque appears as an important factor associated with symptomatic ICA disease. Also, young patients are more likely to have an echolucent plaque suggesting an age-related association with plaque maturation.

Basic study on estimation method of wall shear stress in common carotid artery using blood flow imaging

2020 ◽  
Vol 59 (SK) ◽  
pp. SKKE16 ◽  
Author(s):  
Ryo Nagaoka ◽  
Kazuma Ishikawa ◽  
Michiya Mozumi ◽  
Magnus Cinthio ◽  
Hideyuki Hasegawa
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Carotid Artery ◽  
Wall Shear Stress ◽  
Common Carotid Artery ◽  
Estimation Method ◽  
Flow Imaging ◽  
Basic Study ◽  
Blood Flow Imaging ◽  
Wall Shear

The Association Between Cardio-Ankle Vascular Index and Primary Idiopathic Complete Atrioventricular Block in an Elderly Population

Angiology ◽  
2021 ◽  
pp. 000331972110287
Author(s):  
Turhan Turan ◽  
Faruk Kara ◽  
Selim Kul ◽  
Muhammet Rasit Sayın ◽  
Sinan Sahin ◽  
...  
Keyword(s):  
Arterial Stiffness ◽  
Atrioventricular Block ◽  
Elderly Population ◽  
Complete Atrioventricular Block ◽  
Age Related ◽  
And Gender ◽  
The Relationship ◽  
Block Frequency ◽  
Complete Atrioventricular ◽  
Relevant Factors

The most common cause of complete atrioventricular block (CAVB) is age-related fibrotic degeneration and is referred to as primary idiopathic complete atrioventricular block (iCAVB). This study aims to investigate the relationship between iCAVB and arterial stiffness using the cardio-ankle vascular index (CAVI). In this study, of 205 CAVB patients, 41 patients with iCAVB implanted with a dual-chamber permanent pacemaker and 40 age- and gender-matched controls were studied. Arterial stiffness was assessed by a VaSera VS-1000 CAVI instrument. The CAVI values of patients with iCAVB were significantly higher compared with the controls (9.63 ± 1.42 vs 8.57 ± 1.12, P < .001). Idiopathic complete atrioventricular block frequency was higher among patients with abnormal CAVI values than those with borderline and normal CAVI ( P = .04). In multivariate analysis, only CAVI was an independent predictor of iCAVB after adjusting for other relevant factors (odds ratio, 2.575; 95% CI [1.390-4.770]; P = .003). The present study demonstrated that CAVI, as a marker of arterial stiffness, was increased among elderly patients with iCAVB. Thus, we provide a possible additional mechanism linking easily measured CAVI with iCAVB.

scholarly journals Aging-associated deficit in CCR7 is linked to worsened glymphatic function, cognition, neuroinflammation, and β-amyloid pathology

2021 ◽  
Vol 7 (21) ◽  
pp. eabe4601
Author(s):  
Sandro Da Mesquita ◽  
Jasmin Herz ◽  
Morgan Wall ◽  
Taitea Dykstra ◽  
Kalil Alves de Lima ◽  
...  
Keyword(s):  
T Cells ◽  
Cognitive Decline ◽  
Brain Aging ◽  
Therapeutic Potential ◽  
T Cell Response ◽  
Age Related ◽  
Lymphatic Vasculature ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Old Mice

Aging leads to a progressive deterioration of meningeal lymphatics and peripheral immunity, which may accelerate cognitive decline. We hypothesized that an age-related reduction in C-C chemokine receptor type 7 (CCR7)–dependent egress of immune cells through the lymphatic vasculature mediates some aspects of brain aging and potentially exacerbates cognitive decline and Alzheimer’s disease–like brain β-amyloid (Aβ) pathology. We report a reduction in CCR7 expression by meningeal T cells in old mice that is linked to increased effector and regulatory T cells. Hematopoietic CCR7 deficiency mimicked the aging-associated changes in meningeal T cells and led to reduced glymphatic influx and cognitive impairment. Deletion of CCR7 in 5xFAD transgenic mice resulted in deleterious neurovascular and microglial activation, along with increased Aβ deposition in the brain. Treating old mice with anti-CD25 antibodies alleviated the exacerbated meningeal regulatory T cell response and improved cognitive function, highlighting the therapeutic potential of modulating meningeal immunity to fine-tune brain function in aging and in neurodegenerative diseases.

Low-dose aspirin prevents age-related endothelial dysfunction in a mouse model of physiological aging

2008 ◽  
Vol 294 (4) ◽  
pp. H1562-H1570 ◽  
Author(s):  
Hélène Bulckaen ◽  
Gaétan Prévost ◽  
Eric Boulanger ◽  
Géraldine Robitaille ◽  
Valérie Roquet ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Protective Effect ◽  
Structural Changes ◽  
Low Dose ◽  
Age Groups ◽  
Dose Aspirin ◽  
Age Related ◽  
Low Dose Aspirin ◽  
Old Mice

The age-related impairment of endothelium-dependent vasodilatation contributes to increased cardiovascular risk in the elderly. For primary and secondary prevention, aspirin can reduce the incidence of cardiovascular events in this patient population. The present work evaluated the effect of low-dose aspirin on age-related endothelial dysfunction in C57B/J6 aging mice and investigated its protective antioxidative effect. Age-related endothelial dysfunction was assessed by the response to acetylcholine of phenylephrine-induced precontracted aortic segments isolated from 12-, 36-, 60-, and 84-wk-old mice. The effect of low-dose aspirin was examined in mice presenting a decrease in endothelial-dependent relaxation (EDR). The effects of age and aspirin treatment on structural changes were determined in mouse aortic sections. The effect of aspirin on the oxidative stress markers malondialdehyde and 8-hydroxy-2′-deoxyguanosine (8-OhdG) was also quantified. Compared with that of 12-wk-old mice, the EDR was significantly reduced in 60- and 84-wk-old mice ( P < 0.05); 68-wk-old mice treated with aspirin displayed a higher EDR compared with control mice of the same age (83.9 ± 4 vs. 66.3 ± 5%; P < 0.05). Aspirin treatment decreased 8-OHdG levels ( P < 0.05), but no significant effect on intima/media thickness ratio was observed. The protective effect of aspirin was not observed when treatment was initiated in older mice (96 wk of age). It was found that low-dose aspirin is able to prevent age-related endothelial dysfunction in aging mice. However, the absence of this effect in the older age groups demonstrates that treatment should be initiated early on. The underlying mechanism may involve the protective effect of aspirin against oxidative stress.

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