Elastin Density Research Articles

Effects of age, elastin density, and glycosaminoglycan accumulation on the delamination strength of human thoracic and abdominal aortas

Aortic dissection is a life-threatening condition caused by layer separation. Despite extensive research, the relationship between the aortic wall's structural integrity and dissection risk remains unclear. Glycosaminoglycan (GAG) accumulation and elastin loss are suspected to play significant roles. We investigated how age-related changes in aortic structure affect dissection susceptibility. Peeling tests were performed on longitudinal and circumferential thoracic (TA) and abdominal aortic (AA) strips from 35 donors aged 13–76 years (mean 38 ± 15 years, 34 % female). GAG, elastin, collagen, and smooth muscle cell (SMC) contents were assessed using bidirectional histology. Young TAs resisted longitudinal peeling better than circumferential, with delamination strengths of 65.4 mN/mm and 44.2 mN/mm, respectively. Delamination strength decreased with age in both directions, more rapidly longitudinally, equalizing at ∼20–25 mN/mm in older TAs. Delamination strength in AAs was 22 % higher than in TAs. No sex differences were observed. GAG density increased, while elastin density decreased by 2.5 % and 4 % per decade, respectively. Collagen density did not change with age, while SMC density decreased circumferentially. GAGs partially mediated the reduction in longitudinal delamination strength due to aging, while circumferential strength reduction was not mediated by changes in either GAG or elastin densities. This study explains why aortic dissections are more common in TAs, especially in older individuals, and why they typically propagate spirally. TAs exhibit lower delamination strength compared to AAs and experience strength reduction with age, a phenomenon linked to increased GAG accumulation and elastin loss. These findings enhance our understanding of the pathophysiological mechanisms behind aortic dissection. Statement of significanceThis work explores the age-dependent relationships between delamination strength in human aortas and wall structural content. We investigated 35 human aortas from donors aged 13 to 76 years, providing new insights into the biomechanical and histological factors that influence aortic dissection risk. Our findings elucidate how variations in elastin, glycosaminoglycan, collagen, and smooth muscle cell densities impact the structural integrity of the aorta, contributing significantly to the understanding of aortic dissection mechanisms.

Efficacy and safety of bipolar fractional radiofrequency vs. 2940-nm Er:YAG ablative fractional laser in striae distensae treatment: A split abdomen study.

Striae distensae (SD) is a challenging cosmetic condition. Ablative fractional laser (AFL) is an effective method for treating SD. Recently, fractional radiofrequency (FRF) has been shown to be a promising treatment for SD; however, few studies have shown the differences between FRF and AFL in the treatment of SD. This study aimed to evaluate and compare the clinical efficacy and safety of bipolar FRF with 2940-nm erbium yttrium aluminum garnet (Er:YAG) AFL in the treatment of SD. Twenty volunteers with abdominal SD were enrolled in this study. One half of the abdomen was treated with 2940-nm Er:YAG AFL, whereas the other half was treated with bipolar FRF, with three sessions at 4-week intervals. Photographic evaluations of clinical improvement were conducted by two independent investigators before and after treatment, and the patients provided self-assessments. Two participants underwent three punch biopsies, one before treatment and two obtained from bilateral representative skin lesions on the abdomen 3 months following the final treatment. Clinical improvements were observed in SD on both sides of the abdomen after the two treatments. Post-treatment skin biopsies revealed increased thickness in the epidermis and dermis, and higher collagen and elastin density compared to those at the baseline. No statistically significant differences were observed in the clinical outcomes between the two treatment approaches. The efficacy and safety of bipolar FRF treatment are comparable to those of 2940-nm Er:YAG AFL treatment, providing an alternative and effective treatment for SD.

Variability in structure, morphology, and mechanical properties of the descending thoracic and infrarenal aorta around their circumference

Aortic diseases, such as aneurysms, atherosclerosis, and dissections, demonstrate a preferential development and progression around the aortic circumference, resulting in a highly heterogeneous disease state around the circumference. Differences in the aorta's structural composition and mechanical properties may be partly responsible for this phenomenon. Our goal in this study was to analyze the mechanical and structural properties of the human aorta at its lateral, anterior, posterior, and medial quadrants in two regions prone to circumferentially inhomogeneous diseases, descending Thoracic Aorta (TA) and Infrarenal Aorta (IFR). Human aortas were obtained from 10 donors (64 ± 11 years) and dissected from their loose surrounding tissue. Mechanical properties were determined in all four quadrants of TA and IFR using planar biaxial testing and fitted to three common constitutive models. The structure of tissues was assessed using Movat Pentachrome stained histology slides. We observed that the anterior quadrant exhibited the greatest thickness, followed by the lateral region, in both the TA and IFR. In TA, the posterior wall appeared as the stiffest location in most samples, while in IFR, the anterior wall was the stiffest. We observed a higher glycosaminoglycans content in the lateral and posterior regions of the IFR. We found elastin density to be similar in TA lateral, anterior, and posterior quadrants, while in IFR, the anterior region demonstrated the highest elastin density. Despite significant variations between subjects, this study highlights the distinct morphometrical, mechanical, and structural properties between the quadrants of both TA and IFR.

(090) Immunohistochemical Staining of Elastin in the Vestibule

Abstract Introduction The vestibule is an external genital structure lying 90° to the vaginal canal opening. During the thrusting movements associated with penetrative sexual activity, the vestibule undergoes significant stretching during both invagination and evagination. The vestibule also undergoes extreme stretching during childbirth. The rete pegs in the non-keratinized squamous epithelium facilitate the ability of the vestibule to mechanically stretch. More importantly, however, the vestibular lamina propria, with nerves, blood vessels, glands, needs to contain a high density of extracellular matrix (ECM) proteins with stretching capabilities. In particular, the ECM protein elastin endows skin structures with the ability to stretch, recoil, and have elasticity. Elastin has previously been shown to influence mechanical stretching properties of tendons. Objective The objective of this study was to examine the density of elastin proteins in the vestibule in reproductive age patients as there are currently limited data. Methods A total of 7 reproductive age patients with normal sex steroid hormone values and complaints of entrance dyspareunia were diagnosed with neuroproliferative vestibulodynia and subsequently underwent complete vestibulectomy. Tissue blocks were created from the specimen, and 5 μm sections studied with immunohistochemical staining with primary antibody. Sections were then counterstained with Gill-modified hematoxylin. Results In all vestibular specimen, there was very high density of elastin underneath the epithelium in rete pegs and throughout the entire lamina propria (Fig 1). There is a density gradient with the highest density immediately deep to the basement membrane of the epithelium. Elastin fibers were arranged in all orientations: coronal (frontal), sagittal (longitudinal), and transverse (axial) planes. Conclusions The high density of elastin fibers in rete pegs and throughout the lamina propria in a multi-planar orientation is suggestive of extreme stretching capability in eugonadal vestibular tissues. The highest density of elastin staining was seen immediately below the basement membrane of the epithelium, which may provide tissue integrity and shear resilience to the epithelial layer. In sex steroid hormone insufficiency states such as menopause or with use of combined hormonal contraceptives, individuals may develop loss of introital elasticity and fissures due to a deficiency of the ECM protein elastin. More research is needed on elastic fiber production, organization, and integration with other cutaneous extracellular matrix proteins, and how they may be affected by sex steroid hormones. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Endoceutics, Inc.

MP27-14 ELASTIN STAINING OF THE VESTIBULE

You have accessJournal of UrologyCME1 Apr 2023MP27-14 ELASTIN STAINING OF THE VESTIBULE Alyssa Yee, Alain Dury, Johanne Ouellet, Barry Komisaruk, Sue W Goldstein, and Irwin Goldstein Alyssa YeeAlyssa Yee More articles by this author , Alain DuryAlain Dury More articles by this author , Johanne OuelletJohanne Ouellet More articles by this author , Barry KomisarukBarry Komisaruk More articles by this author , Sue W GoldsteinSue W Goldstein More articles by this author , and Irwin GoldsteinIrwin Goldstein More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003255.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The vestibule is an external genital structure lying 90° to the vaginal canal opening. The vestibule consists of non-keratinized squamous epithelium with numerous rete pegs, underlying lamina propria with nerves, blood vessels, glands, and extracellular matrix (ECM) proteins. During thrusting movements associated with penetrative sexual activity, the vestibule undergoes significant stretching during invagination/evagination. The vestibule also undergoes extreme stretching during childbirth. Elastin is an ECM protein in microfibrils that endows skin structures with ability to stretch, recoil, and have elasticity. Elastin has previously been shown to influence mechanical properties of tendons; degraded or abnormal elastin structures caused by aging or disease may contribute to pain and increased risk of injury. There are limited data on elastin in the vestibule in reproductive age patients and its role in vestibular elasticity/integrity. METHODS: 7 reproductive age patients with entrance dyspareunia from neuroproliferative vestibulodynia, with normal values of testosterone, estradiol, and progesterone, underwent complete vestibulectomy. Tissue blocks were created from the specimen, and 5 υm sections studied with IHC primary antibody. Finally, sections were counterstained with Gill-modified hematoxylin. RESULTS: In all vestibular specimen, there was very high density of elastin underneath the epithelium in rete pegs and throughout the entire lamina propria. There is a density gradient with the highest density immediately deep to the basement membrane of the epithelium. Elastin fibers were arranged in all orientations: coronal (frontal), sagittal (longitudinal), and transverse (axial) planes. CONCLUSIONS: The high density of elastin fibers in rete pegs and through the lamina propria in a multi-planar orientation is suggestive of extreme stretching capability in eugonadal vestibular tissues. The highest density of elastin staining was seen immediately below the basement membrane of the epithelium, which may provide tissue integrity and shear resilience to the epithelial layer. More research is needed on elastic fiber production, organization, and integration with other cutaneous extracellular matrix proteins, and how this may change during androgen insufficiency states such as menopause or with use of combined hormonal contraceptives. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e367 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alyssa Yee More articles by this author Alain Dury More articles by this author Johanne Ouellet More articles by this author Barry Komisaruk More articles by this author Sue W Goldstein More articles by this author Irwin Goldstein More articles by this author Expand All Advertisement PDF downloadLoading ...

Nondestructive Evaluation of Mechanical and Histological Properties of the Human Aorta With Near-Infrared Spectroscopy

IntroductionAscending aortic dilatation is a well-known risk factor for aortic rupture. Indications for aortic replacement in its dilatation concomitant to other open-heart surgery exist; however, cut-off values based solely on aortic diameter may fail to identify patients with weakened aortic tissue. We introduce near-infrared spectroscopy (NIRS) as a diagnostic tool to nondestructively evaluate the structural and compositional properties of the human ascending aorta during open-heart surgeries. During open-heart surgery, NIRS could provide information regarding tissue viability in situ and thus contribute to the decision of optimal surgical repair. Materials and methodsSamples were collected from patients with ascending aortic aneurysm (n = 23) undergoing elective aortic reconstruction surgery and from healthy subjects (n = 4). The samples were subjected to spectroscopic measurements, biomechanical testing, and histological analysis. The relationship between the near-infrared spectra and biomechanical and histological properties was investigated by adapting partial least squares regression. ResultsModerate prediction performance was achieved with biomechanical properties (r = 0.681, normalized root-mean-square error of cross-validation = 17.9%) and histological properties (r = 0.602, normalized root-mean-square error of cross-validation = 22.2%). Especially the performance with parameters describing the aorta's ultimate strength, for example, failure strain (r = 0.658), and elasticity (phase difference, r = 0.875) were promising and could, therefore, provide quantitative information on the rupture sensitivity of the aorta. For the estimation of histological properties, the results with α-smooth muscle actin (r = 0.581), elastin density (r = 0.973), mucoid extracellular matrix accumulation(r = 0.708), and media thickness (r = 0.866) were promising. ConclusionsNIRS could be a potential technique for in situ evaluation of biomechanical and histological properties of human aorta and therefore useful in patient-specific treatment planning.

In vivo multiphoton multiparametric 3D quantification of human skin aging on forearm and face

Quantifying skin aging changes and characterizing its 3D structure and function in a non-invasive way is still a challenging area of research, constantly evolving with the development of imaging methods and image analysis tools. In vivo multiphoton imaging offers means to assess skin constituents in 3D, however prior skin aging studies mostly focused on 2D analyses of dermal fibers through their signals’ intensities or densities. In this work, we designed and implemented multiphoton multiparametric 3D quantification tools for in vivo human skin pigmentation and aging characterization. We first demonstrated that despite the limited field of view of the technic, investigation of 2 regions of interest (ROIs) per zone per volunteer is a good compromise in assessing 3D skin constituents in both epidermis and superficial dermis. We then characterized skin aging on different UV exposed areas—ventral and dorsal forearms, face. The three major facts of aging that are epidermal atrophy, the dermal–epidermal junction (DEJ) flattening and dermal elastosis can be non-invasively quantified and compared. Epidermal morphological changes occur late and were only objectified between extreme age groups. Melanin accumulation in suprabasal layers with age and chronic exposure on ventral and dorsal forearms is less known and appears earlier. Superficial dermal aging changes are mainly elastin density increase, with no obvious change in collagen density, reflected by SHGto2PEF ratio and SAAID index decrease and ImbrN index increase on all skin areas. Analysis of the z-dermal distribution of these parameters highlighted the 2nd 20 µm thickness normalized dermal sub-layer, that follows the DEJ shape, as exhibiting the highest aging differences. Moreover, the 3D ImbrN index allows refining the share of photoaging in global aging on face and the 3D SAAID index on forearm, which elastin or fibrillar collagens densities alone do not allow. Photoaging of the temple area evolves as a function of chronic exposure with a more pronounced increase in elastin density, also structurally modified from thin and straight elastic fibers in young volunteers to dense and compact pattern in older ones. More generally, multiphoton multiparametric 3D skin quantification offers rich spatial information of interest in assessing normal human skin condition and its pathological, external environment or product induced changes.

Effects of corticosteroids vs halofuginone on vocal fold wound healing in an ovine model.

ObjectivesTo evaluate antifibrotic effects of corticosteroids and halofuginone, a small molecule inhibitor of Smad3, in an ovine model of vocal fold (VF) injury.MethodsThirty sheep, using a paired study design, underwent controlled right VF injury by biopsy and then were treated with either no treatment, oral dexamethasone, intralesional triamcinolone, or oral halofuginone. Larynges were evaluated for histological evidence of fibrosis, immunohistochemical presence of Smad3, and vibratory parameters. Outcomes were compared across treatment groups.ResultsFollowing injury, VF collagen density decreased in both halofuginone‐treated and dexamethasone‐treated sheep but not in triamcinolone treated sheep. A significant difference was noted between halofuginone and triamcinolone treated sheep (27.8% vs 37%, P = .017). Elastin was preserved postinjury by halofuginone treatment in contrast with all steroid treated animals where significant loss of elastin was noted (P <.05). Smad3 staining was up‐regulated at all injury sites compared to normal left VFs however halofuginone and dexamethasone treatment reduced Smad3 activity significantly whereas triamcinolone treatment did not (P <.05). Ex‐vivo stroboscopic evaluation demonstrated mucosal wave in all excised larynges with a normalized glottal gap less than 3, suggesting adequate glottal closure.ConclusionsVF injury in an ovine model results in a wound response able to be modified by Smad3 inhibitor, halofuginone, with benefit to vibratory function. Halofuginone treated sheep demonstrated reduced collagenization of lamina propria with greater elastin density after injury, than sheep treated with either steroid medication. These data support this pathway as a suitable target for manipulation to prevent or reverse fibrosis in the glottis and restore voice quality.Level of Evidence: NA.

Pulmonary haemodynamic effects of interatrial shunt in heart failure with preserved ejection fraction: a preclinical study.

The aim of this study was to evaluate the effect of the creation of a left-to-right interatrial shunt on pulmonary haemodynamics in rats with heart failure with preserved ejection fraction (HFPEF). An interatrial communication (IAC) was created in 11 healthy rats (Lewis rats) and 11 rats which developed HFPEF (36-week-old spontaneously hypertensive rats [SHR]). Effects of the interatrial shunt were compared to 11 sham-operated Lewis and 11 sham-operated SHR. At 45 days post shunt, strain effect was observed in diastolic function (E/A ratio, p<0.001; isovolumetric relaxation time, p<0.001), left atrial volume (p=0.005) and pulmonary wall shear rate (WSR) (p=0.02) measured by Doppler echo. At sacrifice of the animals (60 days), a strain effect was also noted in elastin density (p=0.003) and eNOS protein expression (p=0.001). Interatrial shunt creation resulted in (i) an increase in pulmonary WSR (p=0.04) and a decrease in left atrial volume (p<0.001), (ii) an increase in elastin density (p<0.005), and (iii) an increase in eNOS protein expression (p=0.03). Creation of a left-to-right atrial shunt in rats with HFPEF was effective in improving pulmonary haemodynamics. In addition, this study provides preliminary evidence of the potential risk of right volume overload and pulmonary hypertension due to atrial shunting.

In Vivo Aortic Magnetic Resonance Elastography in Abdominal Aortic Aneurysm: A Validation in an Animal Model.

Using maximum diameter of an abdominal aortic aneurysm (AAA) alone for management can lead to delayed interventions or unnecessary urgent repairs. Abdominal aortic aneurysm stiffness plays an important role in its expansion and rupture. In vivo aortic magnetic resonance elastography (MRE) was developed to spatially measure AAA stiffness in previous pilot studies and has not been thoroughly validated and evaluated for its potential clinical value. This study aims to evaluate noninvasive in vivo aortic MRE-derived stiffness in an AAA porcine model and investigate the relationships between MRE-derived AAA stiffness and (1) histopathology, (2) uniaxial tensile test, and (3) burst testing for assessing MRE's potential in evaluating AAA rupture risk. Abdominal aortic aneurysm was induced in 31 Yorkshire pigs (n = 226 stiffness measurements). Animals were randomly divided into 3 cohorts: 2-week, 4-week, and 4-week-burst. Aortic MRE was sequentially performed. Histopathologic analyses were performed to quantify elastin, collagen, and mineral densities. Uniaxial tensile test and burst testing were conducted to measure peak stress and burst pressure for assessing the ultimate wall strength. Magnetic resonance elastography-derived AAA stiffness was significantly higher than the normal aorta. Significant reduction in elastin and collagen densities as well as increased mineralization was observed in AAAs. Uniaxial tensile test and burst testing revealed reduced ultimate wall strength. Magnetic resonance elastography-derived aortic stiffness correlated to elastin density (ρ = -0.68; P < 0.0001; n = 60) and mineralization (ρ = 0.59; P < 0.0001; n = 60). Inverse correlations were observed between aortic stiffness and peak stress (ρ = -0.32; P = 0.0495; n = 38) as well as burst pressure (ρ = -0.55; P = 0.0116; n = 20). Noninvasive in vivo aortic MRE successfully detected aortic wall stiffening, confirming the extracellular matrix remodeling observed in the histopathologic analyses. These mural changes diminished wall strength. Inverse correlation between MRE-derived aortic stiffness and aortic wall strength suggests that MRE-derived stiffness can be a potential biomarker for clinically assessing AAA wall status and rupture potential.

Bilaminar Structure of the Human Optic Nerve Sheath

ABSTRACT Purpose/Aim We aimed to characterize the connective tissue microanatomy, elastin abundance, and fiber orientation in the human optic nerve sheath, also known as the optic nerve dura mater, for correlation with its biomechanical properties. Materials and Methods Seven whole human orbits aged 4–93 years, and five isolated human optic nerve sheaths aged 26–75 years were formalin fixed, paraffin embedded, coronally sectioned, stained by Masson trichrome and van Gieson’s elastin methods, and analyzed quantitatively for elastin fiber abundance and orientation. Elastin area fraction was defined as area stained for elastin divided by total area. Results While unilaminar in children, the adult ON sheath exhibited distinct inner and outer layers. Collagen was denser and more compact in the inner layer. Elastin area fraction was significantly greater at 6.0 ± 0.4% (standard error of mean) in the inner than outer layer at 3.6 ± 0.4% (P < 10−5). Elastin fibers had three predominant orientations: longitudinal, diagonal, and circumferential. Of circumferential fibers, 63 ± 4.7% were in the inner and 37 ± 4.7% in the outer layer (P < 10−4). Longitudinal and diagonal fibers were uniformly distributed in both layers. Elastin density and sheath thickness increased significantly with age (P < .01). Conclusions The adult human optic nerve sheath is bilaminar, with each layer containing elastin fibers oriented in multiple directions consistent with isotropic properties. Differences in laminar elastin density and orientation may reflect greater tensile loading in the inner than in the outer layer.

Is Umbilical Cord Blood Therapy an Effective Treatment for Early Lung Injury in Growth Restriction?

Fetal growth restriction (FGR) and prematurity are often co-morbidities, and both are risk factors for lung disease. Despite advances in early delivery combined with supportive ventilation, rates of ventilation-induced lung injury (VILI) remain high. There are currently no protective treatments or interventions available that target lung morbidities associated with FGR preterm infants. Stem cell therapy, such as umbilical cord blood (UCB) cell administration, demonstrates an ability to attenuate inflammation and injury associated with VILI in preterm appropriately grown animals. However, no studies have looked at the effects of stem cell therapy in growth restricted newborns. We aimed to determine if UCB treatment could attenuate acute inflammation in the first 24 h of ventilation, comparing effects in lambs born preterm following FGR with those born preterm but appropriately grown (AG). Placental insufficiency (FGR) was induced by single umbilical artery ligation in twin-bearing ewes at 88 days gestation, with twins used as control (appropriately grown, AG). Lambs were delivered preterm at ~126 days gestation (term is 150 days) and randomized to either immediate euthanasia (unventilated controls, AGUVC and FGRUVC) or commenced on 24 h of gentle supportive ventilation (AGV and FGRV) with additional cohorts receiving UCB treatment at 1 h (AGCELLS, FGRCELLS). Lungs were collected at post-mortem for histological and biochemical examination. Ventilation caused lung injury in AG lambs, as indicated by decreased septal crests and elastin density, as well as increased inflammation. Lung injury in AG lambs was attenuated with UCB therapy. Ventilated FGR lambs also sustained lung injury, albeit with different indices compared to AG lambs; in FGR, ventilation reduced septal crest density, reduced alpha smooth muscle actin density and reduced cell proliferation. UCB treatment in ventilated FGR lambs further decreased septal crest density and increased collagen deposition, however, it increased angiogenesis as evidenced by increased vascular endothelial growth factor (VEGF) expression and vessel density. This is the first time that a cell therapy has been investigated in the lungs of growth restricted animals. We show that the uterine environment can alter the response to both secondary stress (ventilation) and therapy (UCB). This study highlights the need for further research on the potential impact of novel therapies on a growth restricted offspring.

Mechanical and structural changes in human thoracic aortas with age

Aortic mechanical and structural characteristics have profound effects on pathophysiology, but many aspects of physiologic stress-stretch state and intramural changes due to aging remain poorly understood in human tissues. While difficult to assess in vivo due to residual stresses and pre-stretch, physiologic stress-stretch characteristics can be calculated using experimentally-measured mechanical properties and constitutive modeling. Mechanical properties of 76 human descending thoracic aortas (TA) from 13 to 78-year-old donors (mean age 51±18 years) were measured using multi-ratio planar biaxial extension. Constitutive parameters were derived for aortas in 7 age groups, and the physiologic stress-stretch state was calculated. Intramural characteristics were quantified from histological images and related to aortic morphometry and mechanics. TA stiffness increased with age, and aortas became more nonlinear and anisotropic. Systolic and diastolic elastic energy available for pulsation decreased with age from 30 to 8 kPa and from 18 to 5 kPa, respectively. Cardiac cycle circumferential stretch dropped from 1.14 to 1.04, and circumferential and longitudinal physiologic stresses decreased with age from 90 to 72 kPa and from 90 to 17 kPa, respectively. Aortic wall thickness and radii increased with age, while the density of elastin in the tunica media decreased. The number of elastic lamellae and circumferential physiologic stress per lamellae unit remained constant with age at 102±10 and 0.85±0.04 kPa, respectively. Characterization of mechanical, physiological, and structural features in human aortas of different ages can help understand aortic pathology, inform the development of animal models that simulate human aging, and assist with designing devices for open and endovascular aortic repairs. Statement of significanceThis manuscript describes mechanical and structural changes occurring in human thoracic aortas with age, and presents material parameters for 4 commonly used constitutive models. Presented data can help better understand aortic pathology, inform the development of animal models that simulate human aging, and assist with designing devices for open and endovascular aortic repairs.

Quantification of the regional bioarchitecture in the human aorta.

Regional variance in human aortic bioarchitecture responsible for the elasticity of the vessel is poorly understood. The current study quantifies the elements responsible for aortic compliance, namely, elastin, collagen and smooth muscle cells, using histological and stereological techniques on human tissue with a focus on regional heterogeneity. Using donated cadaveric tissue, a series of samples were excised between the proximal ascending aorta and the distal abdominal aorta, for five cadavers, each of which underwent various staining procedures to enhance specific constituents of the wall. Using polarised light microscopy techniques, the orientation of collagen fibres was studied for each location and each tunical layer of the aorta. Significant transmural and longitudinal heterogeneity in collagen fibre orientations were uncovered throughout the vessel. It is shown that a von Mises mixture model is required accurately to fit the complex collagen fibre distributions that exist along the aorta. Additionally, collagen and smooth muscle cell density was observed to increase with increasing distance from the heart, whereas elastin density decreased. Evidence clearly demonstrates that the aorta is a highly heterogeneous vessel which cannot be simplistically represented by a single compliance value. The quantification and fitting of the regional aortic bioarchitectural data, although not without its limitations, including mean cohort age of 77.6years, facilitates the development of next-generation finite element models that can potentially simulate the influence of regional aortic composition and microstructure on vessel biomechanics.

Mechanical characterisation of human ascending aorta dissection

Mechanical characteristics of both the healthy ascending aorta and acute type A aortic dissection were investigated using in vitro biaxial tensile tests, in vivo measurements via transoesophageal echocardiography and histological characterisations. This combination of analysis at tissular, structural and microstructural levels highlighted the following: (i) a linear mechanical response for the dissected intimomedial flap and, conversely, nonlinear behaviour for both healthy and dissected ascending aorta; all showed anisotropy; (ii) a stiffer mechanical response in the longitudinal than in the circumferential direction for the healthy ascending aorta, consistent with the histological quantification of collagen and elastin fibre density; (iii) a link between dissection and ascending aorta stiffening, as revealed by biaxial tensile tests. This result was corroborated by in vivo measurements with stiffness index, β, and Peterson modulus, Ep, higher for patients with dissection than for control patients. It was consistent with histological analysis on dissected samples showing elastin fibre dislocations, reduced elastin density and increased collagen density. To our knowledge, this is the first study to report biaxial tensile tests on the dissected intimomedial flap and in vivo stiffness measurements of acute type A dissection in humans.

Aortic Stiffness Increases More in the Abdominal Than the Thoracic Aorta in Aging Female Monkeys

Most experimental studies on vascular stiffness in aging females have been conducted in rodents. However, the lifespan of rodents is only 2–3 years, limiting clinical relevance to humans, and they do not go through menopause, making it difficult to translate the data to aging women. The hypothesis of this investigation was that this topic would be more relevant in aging non‐human primates, as their lifespan is over 30 years and they do go through menopause. Accordingly, the goal of this investigation was to compare aortic stiffness in young adult (6±1 years old) and old (24±1 years old) female macaques. An additional unique feature was chronically implanting aortic pressure and diameter transducers to permit the study of direct and continuous measurements of aortic stiffness in conscious monkeys after full recovery from surgery. Another unique feature was to examine aortic stiffness in both the thoracic aorta (TA) and the abdominal aorta (AA). Aortic stiffness (β) was calculated as systolic pressure/diastolic pressure)/aortic strain. Aortic stiffness increased more, p&lt;0.05, in both the TA (49%) and AA (71%) in old vs young female monkeys. The greatest increases in aortic stiffness in the old female monkeys was in the AA, as reflected by a 42% greater increase in the AA than the TA. These differences were confirmed histologically measuring collagen and elastin density and disarray. Whereas collagen density increased and elastin density decreased more in old vs young monkeys, the greatest differences were observed in collagen and elastin disarray. For example, elastin disarray increased more in the AA than the TA, and more in old vs young monkeys, e.g., there was a 48% greater increase, p&lt;0.05, in the TA elastin disarray in old vs young monkeys. Thus, aortic stiffness increases more in old vs young females, with larger increases in the abdominal vs the thoracic aorta, with the mechanism involving changes in collagen and elastin density, but more importantly, increases in collagen and elastin disarray.Support or Funding InformationFunding information: NIH R01 HL102472This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Dermal fiber structures and photoaging.

The use of multiphoton imaging has become a standard technique to visualize the dermis fibers as it requires no specific staining. The density and organization of collagen and elastin are common markers of skin intrinsic aging and photoaging; thus, there is a need of grading this skin aging with quantitative indicators able to provide a robust evaluation of the dermis fibers' state. We propose a systematic analysis of multiphoton images of skin biopsies taken on the buttock and the forearm of patients of different ages. The intensity histograms of images were analyzed through their moments, a wavelet decomposition was done, and the wavelet coefficients distribution was fitted by a generalized Gaussian distribution. Different parameters relative to the collagen or elastin densities, organizations, and structures were calculated and exhibit phenomena specific to intrinsic or extrinsic aging. Those indicators could become a standard method to analyze the degree of skin aging (intrinsic or extrinsic) through multiphoton imaging.

Age-Related Changes of Elastic Fibers in Shoulder Capsule of Patients with Glenohumeral Instability: A Pilot Study.

Background Recurrent shoulder dislocations occur much more frequently in adolescents than in the older population but a clear explanation of this incidence does not exist. The aim of the present study was to define the age-related distribution of the elastic fibers (EFs) in the shoulder capsule's extracellular matrix as a factor influencing shoulder instability. Materials and Methods Biopsy specimens were obtained from the shoulder capsule of patients divided preoperatively into three groups: Group 1 consisted of 10 male patients undergoing surgery for unidirectional traumatic anterior instability (TUBS); Group 2 consisted of 10 male patients undergoing surgery for multidirectional instability (MDI); Group 3 represents the control, including 10 patients with no history of instability. In addition to the group as a whole, specific subgroups were analyzed separately on the basis of the age of subjects: > 22 or < to 22 years. All the samples were analyzed by histochemical (Weigert's resorcinol fuchsin and Verhoeff's iron hematoxylin), immunohistochemical (monoclonal antielastin antibody), and histomorphometric methods. Results Both the elastin density and the percentage of area covered by EFs were significantly higher in younger subjects (<22 years old). Furthermore, the elastin density and the percentage of area covered by EFs were significantly higher in specimens of group of patients affected by multidirectional shoulder instability in comparison to the other two groups. Conclusion Data of the present study confirmed the presence of an age-related distribution of EFs in the human shoulder capsule. The greater amount of EFs observed in younger subjects and in unstable shoulders could play an important role in predisposing the joint to first dislocation and recurrence.

Assessment of the efficacy and tolerance of an innovative regenerative serum on cutaneous regeneration, following fractional laser procedure using Erbium:YAG.

Cutaneous regeneration, fractional laser, medical device, cellular proliferation cutaneous changes linked to photoaging are currently treated with physical treatments, such as fractional laser, which may induce epidermal alteration. To determine the efficacy and safety of a regenerative serum (Matricium® , Laboratoire Bioderma, France) after laser procedure. Prospective, double-blind, controlled, and randomized study in subjects with photoaged skin. The regenerative serum of treatment was used after a fractional laser session twice daily for 2months on 1 side of the face and the placebo on the other side. The main variable to determine efficacy was the improvement of clinical signs and histological and immunological results. A superior quality of epidermal regeneration on the treated side compared to the placebo side was observed. Likewise, a superior and faster clinical improvement on static wrinkles was observed on the hemiface on which the regenerative serum was used. After 60days, the investigator and the subjects observed a moderate to significant improvement of the skin on the treated side and a mild to moderate improvement on the placebo side. Histological examinations showed a superior thickness of epidermis and higher cellular proliferation rate (Ki67 markers) as well as a superior thickness of dermis with higher increase in elastin density with the regenerative serum compared to placebo. The use of the regenerative serum after fractional laser on the face accelerated and improved the cutaneous regeneration on both the clinical and histological level and maximized the benefits of the laser procedure.

The Impact of Heat Treatment on Porcine Heart Valve Leaflets

The purpose of this study was to determine the impact of elevated temperature exposure in tissue banking on soft tissues. A secondary objective was to determine the relative ability of various assays to detect changes in soft tissues due to temperature deviations. Porcine pulmonary heart valve leaflets exposed to 37 °C were compared with those incubated at 52 and 67 °C for 10, 30 and 100 min. The analytical methods consisted of (1) viability assessment using the resazurin assay, (2) collagen content using the Sircol assay, and (3) permeability assessment using an electrical conductivity assay. Additionally, histology and two photon microscopy were used to reveal mechanisms of cell and tissue damage. Viability, collagen content, and permeability all decreased following heat treatment. In terms of statistical significance with respect to treatment temperature, cell viability was most affected (p < 0.0001), followed by permeability (p < 0.0001), and then collagen content (p = 0.13). After heat treatment, histology indicated increased apoptosis and two photon microscopy revealed a decrease in collagen fiber organization and an increase in elastin density. These results suggest that measures of cell viability would be best for assessing tissues where the cells are alive and that permeability may be best where cell viability is not intentionally maintained.