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Brazilian Journal of Medical and... Nov 2015Exercise is known to cause a vasodilatory response; however, the correlation between the vasorelaxant response and different training intensities has not been...
Exercise is known to cause a vasodilatory response; however, the correlation between the vasorelaxant response and different training intensities has not been investigated. Therefore, this study evaluated the vascular reactivity and lipid peroxidation after different intensities of swimming exercise in rats. Male Wistar rats (aged 8 weeks; 250-300 g) underwent forced swimming for 1 h whilst tied to loads of 3, 4, 5, 6, and 8% of their body weight, respectively (groups G3, G4, G5, G6 and G8, respectively; n=5 each). Immediately after the test, the aorta was removed and suspended in an organ bath. Cumulative relaxation in response to acetylcholine (10-12-10-4 M) and contraction in response to phenylephrine (10-12-10-5 M) were measured. Oxidative stress was estimated by determining malondialdehyde concentration. The percentages of aorta relaxation were significantly higher in G3 (7.9±0.20), G4 (7.8±0.29), and G5 (7.9±0.21), compared to the control group (7.2±0.04), while relaxation in the G6 (7.4±0.25) and G8 (7.0±0.06) groups was similar to the control group. In contrast, the percentage of contraction was significantly higher in G6 (8.8 ±0.1) and G8 (9.7±0.29) compared to the control (7.1±0.1), G3 (7.3±0.2), G4 (7.2±0.1) and G5 (7.2±0.2%) groups. Lipid peroxidation levels in the aorta were similar to control levels in G3, G4 and G5, but higher in G6 and G8, and significantly higher in G8 (one-way ANOVA). These results indicate a reduction in vasorelaxing activity and an increase in contractile activity in rat aortas after high-intensity exercise, followed by an increase in lipid peroxidation.
Topics: Analysis of Variance; Animals; Aorta; Exercise Test; Heart; Isometric Contraction; Lactic Acid; Lipid Peroxidation; Male; Malondialdehyde; Oxidative Stress; Physical Exertion; Rats, Wistar; Swimming; Vasodilation
PubMed: 26397974
DOI: 10.1590/1414-431X20154397 -
Arteriosclerosis, Thrombosis, and... Aug 2022Aging enhances most chronic diseases but its impact on human aortic tissue in health and in thoracic aortic aneurysms (TAA) remains unclear.
BACKGROUND
Aging enhances most chronic diseases but its impact on human aortic tissue in health and in thoracic aortic aneurysms (TAA) remains unclear.
METHODS
We employed a human aortic biorepository of healthy specimens (n=17) and those that underwent surgical repair for TAA (n=20). First, we performed proteomics comparing aortas of healthy donors to aneurysmal specimens, in young (ie, <60 years of age) and old (ie, ≥60 years of age) subjects. Second, we measured proteins, via immunoblotting, involved in mitophagy (ie, Parkin) and also mitochondrial-induced inflammatory pathways, specifically TLR (toll-like receptor) 9, STING (stimulator of interferon genes), and IFN (interferon)-β.
RESULTS
Proteomics revealed that aging transformed the aorta both quantitatively and qualitatively from health to TAA. Whereas young aortas exhibited an enrichment of immunologic processes, older aortas exhibited an enrichment of metabolic processes. Immunoblotting revealed that the expression of Parkin directly correlated to subject age in health but inversely to subject age in TAA. In TAA, but not in health, phosphorylation of STING and the expression of IFN-β was impacted by aging regardless of whether subjects had bicuspid or tricuspid valves. In subjects with bicuspid valves and TAAs, TLR9 expression positively correlated with subject age. Interestingly, whereas phosphorylation of STING was inversely correlated with subject age, IFN-β positively correlated with subject age.
CONCLUSIONS
Aging transforms the human aortic proteome from health to TAA, leading to a differential regulation of biological processes. Our results suggest that the development of therapies to mitigate vascular diseases including TAA may need to be modified depending on subject age.
Topics: Aging; Aorta; Aortic Aneurysm, Thoracic; Humans; Interferons; Proteome; Ubiquitin-Protein Ligases
PubMed: 35510553
DOI: 10.1161/ATVBAHA.122.317643 -
American Journal of Physiology. Heart... May 2020Renovascular hypertension is characterized by activation of the renin-angiotensin-aldosterone system, blunted natriuretic responses, and elevated sympathetic nerve...
Renovascular hypertension is characterized by activation of the renin-angiotensin-aldosterone system, blunted natriuretic responses, and elevated sympathetic nerve activity. Excess dietary salt intake exaggerates arterial blood pressure (ABP) in multiple models of experimental hypertension. The present study tested whether a high-salt diet exaggerated ABP and vascular dysfunction in a 2-kidney, 1-clip (2K1C) murine model. Male C57BL/6J mice (8-12 wk) were randomly assigned, and fed a 0.1% or 4.0% NaCl diet, and instrumented with telemetry units to measure ABP. Then, the 2K1C model was produced by placing a cuff around the right renal artery. Systolic, diastolic, and mean ABP were significantly higher in mice fed 4.0% vs. 0.1% NaCl at 1 wk but not after 3 wk. Interestingly, 2K1C hypertension progressively increased arterial pulse pressure in both groups; however, the magnitude was significantly greater in mice fed 4.0% vs. 0.1% NaCl at 3 wk. Moreover, pulse wave velocity was significantly greater in 2K1C mice fed 4.0% vs. 0.1% NaCl diet or sham-operated mice fed either diet. Histological assessment of aortas indicated no structural differences among groups. Finally, endothelium-dependent vasodilation was significantly and selectively attenuated in the aorta but not mesenteric arteries of 2K1C mice fed 4.0% NaCl vs. 0.1% NaCl or sham-operated control mice. The findings suggest that dietary salt loading transiently exaggerates 2K1C renovascular hypertension but promotes chronic aortic stiffness and selective aortic vascular dysfunction. High dietary salt exaggerates hypertension in multiple experimental models. Here we demonstrate that a high-salt diet produces a greater increase in arterial blood pressure at 1 wk after induction of 2-kidney, 1-clip (2K1C) hypertension but not at 3 wk. Interestingly, 2K1C mice fed a high-salt diet displayed an exaggerated pulse pressure, elevated pulse wave velocity, and reduced endothelium-dependent vasodilation of the aorta but not mesenteric arteries. These findings suggest that dietary salt may interact with underlying cardiovascular disease to promote selective vascular dysfunction and aortic stiffness.
Topics: Animals; Aorta; Blood Pressure; Endothelium, Vascular; Hypertension, Renovascular; Male; Mice; Mice, Inbred C57BL; Sodium Chloride, Dietary; Vascular Stiffness; Vasoconstriction
PubMed: 32302491
DOI: 10.1152/ajpheart.00601.2019 -
Journal of the Mechanical Behavior of... May 2023The murine aorta is a complex, heterogeneous structure that undergoes large and sometimes asymmetrical deformations under loading. For analytical convenience, mechanical...
The murine aorta is a complex, heterogeneous structure that undergoes large and sometimes asymmetrical deformations under loading. For analytical convenience, mechanical behavior is predominantly described using global quantities that fail to capture critical local information essential to elucidating aortopathic processes. Here, in our methodological study, we used stereo digital image correlation (StereoDIC) to measure the strain profiles of speckle-patterned healthy and elastase-infused, pathological mouse aortas submerged in a temperature-controlled liquid medium. Our unique device rotates two 15-degree stereo-angle cameras that gather sequential digital images while simultaneously performing conventional biaxial pressure-diameter and force-length testing. A StereoDIC Variable Ray Origin (VRO) camera system model is employed to correct for high-magnification image refraction through hydrating physiological media. The resultant Green-Lagrange surface strain tensor was quantified at different blood vessel inflation pressures, axial extension ratios, and after aneurysm-initiating elastase exposure. Quantified results capture large, heterogeneous, inflation-related, circumferential strains that are drastically reduced in elastase-infused tissues. Shear strains, however, were very small on the tissue's surface. Spatially averaged StereoDIC-based strains were generally more detailed than those determined using conventional edge detection techniques.
Topics: Animals; Mice; Aorta; Mechanical Phenomena
PubMed: 36893686
DOI: 10.1016/j.jmbbm.2023.105745 -
Hormones (Athens, Greece) Mar 2021Estrogens have beneficial effects on the cardiovascular system, promoting vasodilation, endothelial cells growth, relaxation, and regulation of blood pressure. Some of...
PURPOSE
Estrogens have beneficial effects on the cardiovascular system, promoting vasodilation, endothelial cells growth, relaxation, and regulation of blood pressure. Some of these effects could be associated with the purinergic system known for the control of vasodilation, inflammation, and platelet function. The aim of our study was the evaluation of ATP, AMP, and adenosine extracellular catabolism, catalyzed by ectonucleoside triphosphate diphosphohydrolase-1 (CD39), ecto-5'-nucleotidase (CD73), and ecto-adenosine deaminase (eADA) in mouse aortas.
METHODS
Extracellular hydrolysis of ATP, AMP, and adenosine was estimated on the aortic surface of 3-month-old female and male C57BL/6 J wild-type (WT) mice, in female WT mouse aortas incubated for 48 h in the presence or absence of 100 nM estradiol, and in WT female mouse and ApoE-/-LDL-R-/- aortas. The conversion of substrates to products was analyzed by high-pressure liquid chromatography (HPLC).
RESULTS
We demonstrated significantly higher adenosine deamination rate in WT male vs. female mice (p = 0.041). We also noted the lower adenosine hydrolysis in aortas exposed to estradiol, as compared with the samples incubated in estradiol-free medium (p = 0.043). Finally, we observed that adenosine conversion to inosine was significantly higher on the surface of ApoE-/-LDL-R-/- aortas compared with WT mice (p = 0.001). No such effects were noted in ATP and AMP extracellular hydrolysis.
CONCLUSION
We conclude that estradiol inhibits the extracellular degradation of adenosine to inosine, which may be an element of its vascular protective effect, as it will lead to an increase in extracellular adenosine concentration. We can also assume that during the development of the atherosclerotic process, the protective role of estradiol in the regulation of adenosine degradation may be obscured by other pathogenic factors.
Topics: Animals; Aorta; Apolipoproteins E; Endothelial Cells; Estradiol; Female; Male; Mice; Mice, Inbred C57BL; Mice, Knockout, ApoE; Nucleotides; Receptors, LDL
PubMed: 32935303
DOI: 10.1007/s42000-020-00242-6 -
Hypertension Research : Official... Nov 2020Mice are the most common animal model to investigate human disease and explore physiology. Mice are practical, cost efficient, and easily used for genetic manipulations.... (Comparative Study)
Comparative Study
Mice are the most common animal model to investigate human disease and explore physiology. Mice are practical, cost efficient, and easily used for genetic manipulations. Although variability in cardiac structure and function among mouse strains is well noted, the effect of mouse strain on vascular stiffness indices is not known. Here, we compared mouse strain-dependent differences in key vascular stiffness indices among frequently used inbred mouse strains-C57Bl/6J, 129S, and Bl6/129S. In young healthy animals, baseline blood pressure and heart rate were identical in all strains, and independent of gender. However, both active in vivo and passive ex vivo vascular stiffness indices exhibited distinct differences. Specifically, both male and female 129S animals demonstrated the highest tensile stiffness, were least responsive to acetylcholine-induced vasorelaxation, and showed the lowest pulse wave velocity (PWV), an index of in vivo stiffness. C57Bl/6J mice demonstrated the highest PWV, lowest tensile stiffness, and the highest response to acetylcholine-induced vasorelaxation. Interestingly, within each strain, female mice had more compliant aortas. C57Bl/6J mice had thinner vessel walls with fewer layers, whereas 129S mice had the thickest walls with the most layers. Values in the Bl6/129S mixed background mice fell between C57Bl/6J and 129S mice. In conclusion, we show that underlying vascular properties of different inbred wild-type mouse strains are distinct, despite superficial similarities in blood pressure. For each genetic modification, care should be taken to identify proper controls, and conclusions might need to be verified in more than one strain to minimize the risk of false positive studies.
Topics: Animals; Aorta; Female; In Vitro Techniques; Male; Mice, Inbred C57BL; Pulse Wave Analysis; Species Specificity; Vascular Stiffness
PubMed: 32409775
DOI: 10.1038/s41440-020-0467-4 -
The Annals of Thoracic Surgery Apr 2018Aortic valve disease increases velocity and changes the way blood enters the aorta. Over time, the biomechanical environment can cause aortic remodelling. We...
BACKGROUND
Aortic valve disease increases velocity and changes the way blood enters the aorta. Over time, the biomechanical environment can cause aortic remodelling. We hypothesized that aortic geometry and wall stress would be different in patients with aortic valve disease compared with controls.
METHODS
We examined 40 patients with aortic sclerosis (n = 10) or mild (n = 10), moderate (n = 10), and severe (n = 10) aortic stenosis, and also 10 control individuals. The thoracic aorta of each individual was reconstructed into a three-dimensional model from computed tomography. We measured geometric variables and used finite element analysis to compute aortic wall stress. Statistical analyses were performed to test our hypothesis.
RESULTS
Aortic wall stress was significantly associated with tortuosity of the descending aorta (r = 0.35, p = 0.01), arch radius (r = 0.49, p < 0.01), ascending aortic diameter (r = 0.59, p < 0.01), and aortic centerline length (r = 0.39, p < 0.01). Wall stress was highest in patients with severe stenosis (p = 0.02), although elevations in wall stress were also noted in those with mild stenosis (p = 0.02), and aortic sclerosis (p = 0.02) compared with controls. Similar trends were observed when we corrected for difference in blood pressure. Total centerline tortuosity was higher in patients with severe aortic stenosis than in controls (p = 0.04), as was descending aorta tortuosity (p = 0.04).
CONCLUSIONS
Aortic geometry is associated with aortic wall stress. Patients with aortic valve disease have higher aortic wall stress than controls, and those with severe aortic stenosis have more tortuous aortas. However, increases in geometric measures and wall stress are not stepwise with increasing disease severity.
Topics: Aged; Aged, 80 and over; Aorta, Thoracic; Aortic Valve; Blood Flow Velocity; Case-Control Studies; Female; Finite Element Analysis; Heart Valve Diseases; Humans; Male; Middle Aged; Tomography, X-Ray Computed
PubMed: 29288661
DOI: 10.1016/j.athoracsur.2017.11.061 -
Redox Biology 2015Vascular aging is associated with structural and functional modifications of the arteries, and by an increase in arterial wall thickening in the intima and the media,...
Vascular aging is associated with structural and functional modifications of the arteries, and by an increase in arterial wall thickening in the intima and the media, mainly resulting from structural modifications of the extracellular matrix (ECM) components. Among the factors known to accumulate with aging, advanced lipid peroxidation end products (ALEs) are a hallmark of oxidative stress-associated diseases such as atherosclerosis. Aldehydes generated from the peroxidation of polyunsaturated fatty acids (PUFA), (4-hydroxynonenal, malondialdehyde, acrolein), form adducts on cellular proteins, leading to a progressive protein dysfunction with consequences in the pathophysiology of vascular aging. The contribution of these aldehydes to ECM modification is not known. This study was carried out to investigate whether aldehyde-adducts are detected in the intima and media in human aorta, whether their level is increased in vascular aging, and whether elastin fibers are a target of aldehyde-adduct formation. Immunohistological and confocal immunofluorescence studies indicate that 4-HNE-histidine-adducts accumulate in an age-related manner in the intima, media and adventitia layers of human aortas, and are mainly expressed in smooth muscle cells. In contrast, even if the structure of elastin fiber is strongly altered in the aged vessels, our results show that elastin is not or very poorly modified by 4-HNE. These data indicate a complex role for lipid peroxidation and in particular for 4-HNE in elastin homeostasis, in the vascular wall remodeling during aging and atherosclerosis development.
Topics: Adult; Aged; Aged, 80 and over; Aging; Aldehydes; Aorta; Atherosclerosis; Autopsy; Elastin; Extracellular Matrix; Fatty Acids, Unsaturated; Female; Humans; Lipid Peroxidation; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress
PubMed: 25553420
DOI: 10.1016/j.redox.2014.12.008 -
Scientific Reports Mar 2022Vascular smooth muscle cells are exposed to interstitial flow across aortic walls. Fluid shear stress changes the phenotype of smooth muscle cells to the synthetic type;...
Vascular smooth muscle cells are exposed to interstitial flow across aortic walls. Fluid shear stress changes the phenotype of smooth muscle cells to the synthetic type; hence, the fast interstitial flow might be related to aortic diseases. In this study, we propose a novel method to directly measure the interstitial flow velocity from the spatiotemporal changes in the concentration of a fluorescent dye. The lumen of a mouse thoracic aorta was filled with a fluorescent dye and pressurized in ex vivo. The flow of the fluorescent dye from the intimal to the adventitial sides was successfully visualized under a two-photon microscope. The flow velocity was determined by applying a one-dimensional advection-diffusion equation to the kymograph obtained from a series of fluorescent images. The results confirmed a higher interstitial flow velocity in the aortic walls under higher intraluminal pressure. A comparison of the interstitial flow velocity in the radial direction showed faster flow on the more intimal side, where hyperplasia is often found in hypertension. These results indicate that the proposed method can be used to visualize the interstitial flow directly and thus, determine the local interstitial flow velocity.
Topics: Animals; Aorta; Aorta, Thoracic; Aortic Diseases; Blood Flow Velocity; Mice; Myocytes, Smooth Muscle
PubMed: 35354879
DOI: 10.1038/s41598-022-09304-8 -
Theranostics 2018Aortic wall remodelling is a key feature of both ageing and genetic connective tissue diseases, which are associated with vasculopathies such as Marfan syndrome (MFS)....
Aortic wall remodelling is a key feature of both ageing and genetic connective tissue diseases, which are associated with vasculopathies such as Marfan syndrome (MFS). Although the aorta is a 3D structure, little attention has been paid to volumetric assessment, primarily due to the limitations of conventional imaging techniques. Phase-contrast microCT is an emerging imaging technique, which is able to resolve the 3D micro-scale structure of large samples without the need for staining or sectioning. Here, we have used synchrotron-based phase-contrast microCT to image aortae of wild type (WT) and MFS mice aged 3, 6 and 9 months old (n=5). We have also developed a new computational approach to automatically measure key histological parameters. This analysis revealed that WT mice undergo age-dependent aortic remodelling characterised by increases in ascending aorta diameter, tunica media thickness and cross-sectional area. The MFS aortic wall was subject to comparable remodelling, but the magnitudes of the changes were significantly exacerbated, particularly in 9 month-old MFS mice with ascending aorta wall dilations. Moreover, this morphological remodelling in MFS aorta included internal elastic lamina surface breaks that extended throughout the MFS ascending aorta and were already evident in animals who had not yet developed aneurysms. Our 3D microCT study of the sub-micron wall structure of whole, intact aorta reveals that histological remodelling of the tunica media in MFS could be viewed as an accelerated ageing process, and that phase-contrast microCT combined with computational image analysis allows the visualisation and quantification of 3D morphological remodelling in large volumes of unstained vascular tissues.
Topics: Aging; Animals; Aorta; Cross-Sectional Studies; Disease Models, Animal; Imaging, Three-Dimensional; Marfan Syndrome; Mice; Microscopy, Phase-Contrast; X-Ray Microtomography
PubMed: 30613281
DOI: 10.7150/thno.26598