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      Hemodynamics and pathology of an enlarging abdominal aortic aneurysm model in rabbits

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          Abstract

          Hemodynamics may play an essential role in the initiation and progression of abdominal aortic aneurysm (AAA). We aimed to study the mechanism of self-healing process by the changes of hemodynamics and pathology in an enlarging AAA in rabbits. Seventy-two rabbits were randomly divided into three groups. Rabbits underwent extrinsic coarctation and received a 10-minute elastase incubation in Group A and Group B. Absorbable suture used in Group A was terminated by balloon dilation at week 4. Diameter was measured after 1, 3, 5, and 15 weeks, computational fluid dynamics analysis was performed at week 3 and week 15. Rabbits were sacrificed after 1, 5, and 15 weeks for pathological and quantitative studies. The higher velocity magnitude, intensified bulk flow and obvious vortex formation were observed in Group A at week 3 instead of week 15. Both low wall shear stress and high relative residence time increased in Group B, however, high oscillatory shear index had relatively less increase compared with Group A. Aortic diameter reached a plateau at 5 weeks in Group A, which was significantly lower than in week 15 in Group B. Intimal hyperplasia, intima-media thickness increased significantly in Group A at week 5, significantly higher than in week 15 in Group B. Marked destruction of elastin fibers and smooth muscle cells occurred at week 1, and increased significantly at week 15 in Group A. Aneurysm exhibited strong expression of matrix metalloproteinase 9 and mouse anti-rabbit macrophage 11 at week 1, and showed a tendency to decrease. Matrix metalloproteinase 2 expression decreased significantly in Group B at week 15 compared with week 5 and Group A. In conclusion, the self-healing of rabbit AAA may attributed to the regeneration of smooth muscle cells. The turbulence flow caused by coarctation is associated with continuous growth of rabbit AAA and prevents the self-healing phenomenon.

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          Inflammation and cellular immune responses in abdominal aortic aneurysms.

          Expansion and rupture of abdominal aortic aneurysms (AAA) result in high morbidity and mortality rates. Like stenotic atherosclerotic lesions, AAA accumulate inflammatory cells, but usually exhibit much more extensive medial damage. Leukocyte recruitment and expression of pro-inflammatory Th1 cytokines typically characterize early atherogenesis of any kind, and modulation of inflammatory mediators mutes atheroma formation in mice. However, the mechanistic differences between stenotic and aneurysmal manifestations of atherosclerosis remain unexplained. We recently showed that aortic allografts deficient in interferon-gamma (IFN-gamma) signaling developed AAA correlating with skewed Th2 cytokine environments, suggesting important regulatory roles for Th1/Th2 cytokine balance in modulating matrix remodeling and important implications for the pathophysiology of aortic aneurysm and atherosclerosis. Further probing of their distinct aspects of immune and inflammatory responses in vascular diseases should continue to shed new light on the pathophysiologic mechanisms that give rise to aneurysmal versus occlusive manifestations and atherosclerosis.
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            Elastin stabilization for treatment of abdominal aortic aneurysms.

            Maintaining the integrity of arterial elastin is vital for the prevention of abdominal aortic aneurysm (AAA) development. We hypothesized that in vivo stabilization of aortic elastin with pentagalloyl glucose (PGG), an elastin-binding polyphenol, would interfere with AAA development. Safety and efficacy of PGG treatment were first tested in vitro using cytotoxicity, elastin stability, and PGG-elastin interaction assays. For in vivo studies, the efficacy of PGG was evaluated within a well-established AAA model in rats on the basis of CaCl2-mediated aortic injury. With this model, PGG was delivered periadventitially at 2 separate time points during the course of AAA development; aortic diameter, elastin integrity, and other pathological aspects were monitored and evaluated in PGG-treated aortas compared with saline-treated control aortas. Our results show that a one-time periadventitial delivery of noncytotoxic levels of PGG inhibits elastin degeneration, attenuates aneurysmal expansion, and hinders AAA development in rats without interfering with the pathogenic mechanisms typical of this model, namely inflammation, calcification, and high metalloproteinase activities. PGG binds specifically to arterial elastin and, in doing so, preserves the integrity of elastic lamellae despite the presence of high levels of proteinases derived from inflammatory cells. Periadventitial administration of PGG hinders the development of AAA in a clinically relevant animal model. Stabilization of aortic elastin in aneurysm-prone arterial segments offers great potential toward the development of safe and effective therapies for AAAs.
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              Intima–Media Thickness Is Linearly and Continuously Associated With Systolic Blood Pressure in a Population‐Based Cohort (STANISLAS Cohort Study)

              Background Carotid intima–media thickness (cIMT) is a noninvasive marker of cardiovascular risk. The cIMT may be increased in patients with harmonisation, but little is known regarding the functional form of the association between blood pressure (BP) and cIMT in hypertensive and nonhypertensive persons. We aimed to define the shape of the association between BP and cIMT. Methods and Results We studied cIMT and ambulatory BP monitoring data from a single‐center, cross‐sectional, population‐based study involving 696 adult participants from the STANISLAS cohort, a familial longitudinal cohort from the Nancy region of France. Participants with a history of hypertension were more likely to have a cIMT >900 μm and had higher mean cIMT (both P 900 μm increased linearly with higher 24‐hour and daytime systolic BP in participants both with and without history of hypertension. The relationship between systolic BP and the risk of cIMT >900 μm was not dependent on hypertension status (all P for interaction >0.10). In multivariable analysis adjusted on cardiovascular risk factors, each 5‐mm Hg increase in systolic BP was associated with an 8‐μm increase in cIMT (β=8.249 [95% CI 2.490–14.008], P=0.005). In contrast, the association between diastolic BP and cIMT was weaker and not significant. Conclusions Systolic BP is linearly and continuously associated with higher cIMT in both hypertensive and nonhypertensive persons, suggesting a detrimental effect of BP on the vascular tree prior to overt hypertension. Similarly, it suggests a detrimental effect of BP at the higher end of the normal range in treated hypertensive patients. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01391442.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: InvestigationRole: Writing – original draft
                Role: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: Data curationRole: MethodologyRole: Software
                Role: Data curationRole: Formal analysisRole: MethodologyRole: Software
                Role: ConceptualizationRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Project administrationRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                12 October 2018
                2018
                : 13
                : 10
                : e0205366
                Affiliations
                [1 ] Department of Histology and Embryology, College of Basic Medicine, Zhengzhou University, Zhengzhou, China
                [2 ] Department of Ultrasound, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China
                [3 ] Department of Interventional Radiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
                [4 ] Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America
                Max Delbruck Centrum fur Molekulare Medizin Berlin Buch, GERMANY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ‡ These authors are co-first authors on this work.

                Author information
                http://orcid.org/0000-0002-8411-6427
                Article
                PONE-D-18-25604
                10.1371/journal.pone.0205366
                6185729
                30312321
                5ce17a1b-b50e-4156-9a05-3b04aeea5e22
                © 2018 Chen et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 2 September 2018
                : 24 September 2018
                Page count
                Figures: 4, Tables: 0, Pages: 11
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81501569
                Award Recipient :
                This research was supported by National Natural Science Foundation of China (81501569 to YB). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Vertebrates
                Amniotes
                Mammals
                Leporids
                Rabbits
                Research and Analysis Methods
                Animal Studies
                Experimental Organism Systems
                Animal Models
                Rabbits
                Medicine and Health Sciences
                Hematology
                Hemodynamics
                Medicine and Health Sciences
                Vascular Medicine
                Vascular Diseases
                Aneurysms
                Biology and Life Sciences
                Biochemistry
                Proteins
                Elastin
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Muscle Cells
                Smooth Muscle Cells
                Biology and Life Sciences
                Anatomy
                Biological Tissue
                Muscle Tissue
                Muscle Cells
                Smooth Muscle Cells
                Medicine and Health Sciences
                Anatomy
                Biological Tissue
                Muscle Tissue
                Muscle Cells
                Smooth Muscle Cells
                Physical Sciences
                Physics
                Classical Mechanics
                Mechanical Stress
                Shear Stresses
                Physical Sciences
                Physics
                Classical Mechanics
                Continuum Mechanics
                Fluid Mechanics
                Fluid Dynamics
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Custom metadata
                All relevant data are within the manuscript and its Supporting Information files.

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