Fragmentation Of Elastic Fibers Research Articles

Histopathology of the Mitral Valve Residual Leaflet in Obstructive Hypertrophic Cardiomyopathy

BackgroundMitral valve (MV) elongation is a primary hypertrophic cardiomyopathy (HCM) phenotype and contributes to obstruction. The residual MV leaflet that protrudes past the coaptation point is especially susceptible to flow-drag and systolic anterior motion. Histopathological features of MVs in obstructive hypertrophic cardiomyopathy (OHCM), and of residual leaflets specifically, are unknown. ObjectivesThe purpose of this study was to characterize gross, structural, and cellular histopathologic features of MV residual leaflets in OHCM. On a cellular-level, we assessed for developmental dysregulation of epicardium-derived cell (EPDC) differentiation, adaptive endocardial-to-mesenchymal transition and valvular interstitial cell proliferation, and genetically-driven persistence of cardiomyocytes in the valve. MethodsStructural and immunohistochemical staining were performed on 22 residual leaflets excised as ancillary procedures during myectomy, and compared with 11 control leaflets from deceased patients with normal hearts. Structural components were assessed with hematoxylin and eosin, trichrome, and elastic stains. We stained for EPDCs, EPDC paracrine signaling, valvular interstitial cells, endocardial-to-mesenchymal transition, and cardiomyocytes. ResultsThe residual leaflet was always at A2 segment and attached by slack, elongated and curlicued, myxoid chords. MV residual leaflets in OHCM were structurally disorganized, with expanded spongiosa and increased, fragmented elastic fibers compared with control leading edges. The internal collagenous fibrosa was attenuated and there was collagenous tissue overlying valve surfaces in HCM, with an overall trend toward decreased leaflet thickness (1.09 vs 1.47 mm, P = 0.08). No markers of primary cellular processes were identified. ConclusionsMV residual leaflets in HCM were characterized by histologic findings that were likely secondary to chronic hemodynamic stress and may further increase susceptibility to systolic anterior motion.

Pregnancy-associated aortopathy and sudden postpartum death

A 39-year-old woman who had undergone an uncomplicated elective cesarean section for a low-lying placenta collapsed and died the following day. At autopsy, there was dissection of an aneurysmally-dilated thoracic aorta with 400 mls of fluid and clotted blood in the pericardial sac. There were no features of Marfan syndrome or other connective tissue disorders. Histology revealed thinning of the aortic wall with fragmentation of elastic fibers and no inflammation. Vessels elsewhere were normal. This case demonstrates a rare complication of pregnancy that may not present until after delivery with unexpected collapse and sudden death. Predisposing factors include an increased cardiac output, reduction in systemic vascular resistance, an increase in left ventricular muscle mass, and alterations in serum progesterone and estrogen levels which may cause structural changes to the aortic wall. The possibility of syndromic and familial connective tissue disorders should also be considered.

Buried penis: a histological and histochemical study of dartos fascia.

This study aimed to determine whether the abnormal deep layer of dartos fascia plays an important role in buried penis. Forty-nine patients with buried penis were treated with anatomical resection of the deep layer of dartos fascia under a microscope. Penile length was measured before and after completely resecting the deep layer to investigate the role of this layer in penile retraction. The superficial and deep layers of dartos fascia were collected from 49 patients with buried penis, the normal superficial layers were collected from 25 children/adults who underwent circumcision for nonmedical reasons, and the normal deep layers were collected from 20 adult cadavers. The penile fascia samples were stained with hematoxylin-eosin, Masson's trichrome, Sirius red, and Verhoeff's Van Gieson, and subjected to immunohistochemical examination and scanning electron microscopy. The penile shaft (mean ± standard deviation) was found to be significantly elongated after resecting the deep layer compared with that before resection (6.8 ± 1.9 cm vs 6.0 ± 1.6 cm, P < 0.001). An abnormal deep layer of dartos fascia characterized by disordered and fragmented elastic fibers was observed in 87.8% (43/49) of buried penis samples, whereas no abnormal deep layer was observed in normal penises from cadavers (0/20, P < 0.001). Thus, the abnormal deep layer of dartos fascia plays an important role in the buried penis. Its resection is helpful for avoiding recurrence.

A pseudoxanthoma elasticum örökletes ektópiás mineralizációs zavar komplex multidiszciplináris ellátása

The authors summarize the up-to-date knowledge on pseudoxanthoma elasticum, a hereditary connective tissue disorder that results in the fragmentation and mineralization of elastic fibres. Three cases of pseudoxanthoma elasticum under complex dermatological, ophthalmologic and cardiovascular management are described, emphasizing the multidisciplinary aspects of dermatology

High-Frequency Fluctuation Intensity as a Predictor of Post-Stenotic Dilatation in Swine.

To identify the turbulent components of blood flow facilitating aortic lumen dilatation in a post-stenotic dilatation (PSD) porcine model. The porcine abdominal aorta (AA) was moderately coarctated to induce overt flow turbulence in the downstream region and to lead to dilatation in time periods between four and twelve weeks. We propose a new metric, fluctuation intensity (FI), to quantify turbulent fluctuations of pulsatile aortic flow measured within twenty minutes post-coarctation. Lumen perimeter ratio (LPR) of the distal-to-suprarenal AA was used to assess the degree of PSD. Using k-means clustering analysis, we first divided FI frequency spectrum into low- and high-frequency fluctuation intensity (LFFI and HFFI), and subsequently grouped animals with coarctation. Receiver operating characteristic (ROC) analysis was performed to evaluate the ability of the proposed metric to predict PSD. The frequency band of the FI spectrum in facilitating aortic lumen dilatation was identified to be 40∼200 Hz. Using sham group as the reference, pigs receiving coarctation were clustered into two groups with (group A) and without (group B) increases in HFFI values. Coarctation significantly increased LPR values in group A, but not in group B. Moreover, group A exhibited a high probability density distribution on severe elastic fiber fragmentation. ROC analysis indicated HFFI to be capable of predicting PSD with excellent sensitivity and specificity. High-intensity, high-frequency components of blood flow fluctuations induced by moderate coarctation promote elastic lamella degradation and aortic lumen dilatation. HFFI application in flowmeter programs may provide a useful predictor of PSD.

Thoracic aortopathy in Marfan syndrome overlaps with mechanisms seen in bicuspid aortic valve disease.

Thoracic aortopathy is a serious complication which is more often seen in patients with Marfan syndrome (MFS) and patients with a bicuspid aortic valve (BAV) than in individuals with a tricuspid aortic valve (TAV). The identification of common pathological mechanisms leading to aortic complications in non-syndromic and syndromic diseases would significantly improve the field of personalized medicine. This study sought to compare thoracic aortopathy between MFS, BAV, and TAV individuals. Bicuspid aortic valve (BAV; n = 36), TAV (n = 23), and MFS (n = 8) patients were included. Ascending aortic wall specimen were studied for general histologic features, apoptosis, markers of cardiovascular ageing, expression of synthetic and contractile vascular smooth muscle cells (VSMC), and fibrillin-1 expression. The MFS group showed many similarities with the dilated BAV. Both patient groups showed a thinner intima (p < 0.0005), a lower expression of contractile VSMCs (p < 0.05), more elastic fiber thinning (p < 0.001), lack of inflammation (p < 0.001), and a decreased progerin expression (p < 0.05) as compared to the TAV. Other features of cardiovascular ageing differed between the BAV and MFS. Dilated BAV patients demonstrated less medial degeneration (p < 0.0001), VSMC nuclei loss (p < 0.0001), apoptosis of the vessel wall (p < 0.03), and elastic fiber fragmentation and disorganization (p < 0.001), as compared to the MFS and dilated TAV. This study showed important similarities in the pathogenesis of thoracic aortic aneurysms in BAV and MFS. These common mechanisms can be further investigated to personalize treatment strategies in non-syndromic and syndromic conditions.

Histological Skin Assessment of Patients Submitted to Bariatric Surgery: A Prospective Longitudinal Cohort Study.

Obesity is a stigmatizing disease that can cause dermatological aberrations, such as sagging after rapid weight loss. This study is to evaluate the effects of obesity and massive weight loss following bariatric surgery on collagen and elastic fibers of the extracellular matrix of the skin. Thirty-three skin biopsies were collected from patients prior to bariatric surgery and one year after surgery. Histological analyses were performed using hematoxylin-eosin and Weigert's resorcin-fuchsin staining for collagen and elastic and elaunin fibers, respectively. Differences between means were submitted to the Student's t-test or Mann-Whitney U test, with p < 0.05 significant. The study demonstrated an architectural alteration of the skin 1 year after bariatric surgery. In the histological analysis of the skin samples, a significant difference in the thickness of the epidermis was found 1 year after surgery in all age groups as well as in the 38-to-68-kg weight loss group (p < 0.0001). In addition to laxity, disorganization of collagen was found, with an apparent decrease in quantity and an increase in elastic fibers, although fragmented (p < 0.0001). Obesity and massive weight loss following bariatric surgery cause the disorganization of collagen fibers and the fragmentation of elastic fibers of the extracellular matrix of the skin.

Milk Fat Globule Epidermal Growth Factor VIII Fragment Medin in Age-Associated Arterial Adverse Remodeling and Arterial Disease.

Medin, a small 50-amino acid peptide, is an internal cleaved product from the second discoidin domain of milk fat globule epidermal growth factor VIII (MFG-E8) protein. Medin has been reported as the most common amylogenic protein in the upper part of the arterial system, including aortic, temporal, and cerebral arterial walls in the elderly. Medin has a high affinity to elastic fibers and is closely associated with arterial degenerative inflammation, elastic fiber fragmentation, calcification, and amyloidosis. In vitro, treating with the medin peptide promotes the inflammatory phenotypic shift of both endothelial cells and vascular smooth muscle cells. In vitro, ex vivo, and in vivo studies demonstrate that medin enhances the abundance of reactive oxygen species and reactive nitrogen species produced by both endothelial cells and vascular smooth muscle cells and promotes vascular endothelial dysfunction and arterial stiffening. Immunostaining and immunoblotting analyses of human samples indicate that the levels of medin are increased in the pathogenesis of aortic aneurysm/dissection, temporal arteritis, and cerebrovascular dementia. Thus, medin peptide could be targeted as a biomarker diagnostic tool or as a potential molecular approach to curbing the arterial degenerative inflammatory remodeling that accompanies aging and disease.

Pseudoxanthoma Elasticum: A Case Report

BACKGROUND: Pseudoxanthoma elasticum (PXE) is a rare, genetic, metabolic disease with autosomal recessive inheritance caused by mutations in the ABCC6 gene. The lack of functional ABCC6 protein leads to ectopic mineralization that is most apparent in the elastic tissues of the skin, eyes, and blood vessels. Dermatologic manifestations consist of small yellow papules on the nape and sides of the neck and in flexural areas that coalesce into reticulated plaques resembling the cobblestone aspect, and then the skin becomes loose and wrinkled. Histopathologic findings provide characteristic clues such as short, fragmented, clumped, and calcified mid-dermal elastic fibers. CASE PRESENTATION: A 27-year-old Albanian female was referred to the dermatology clinic with skin complaints for approximately 17 years. On physical examination, we observed “cobblestone pattern” lesion located in the anterior, lateral, and posterior aspects of the neck, bilateral axillary, inguinal, antecubital, and popliteal regions, and periumbilical area. A biopsy was performed and the histopathology confirmed the typical changes in the dermis because of ectopic mineralization. The funduscopy revealed the “peau d’orange” aspect, bilateral angioid streaks but no neovascularization. Carotid echography showed minimal intimate thickening with flow acceleration but without significant stenosis of the right common carotid artery (ACC). Different laboratory exams were conducted that resulted within the normal range. CONCLUSION: There is no specific treatment, and therapeutical management is based on prevention, tracking, and follow-ups to increase surveillance of clinical complications through a multidisciplinary team. The dermatologist is usually the first who faces Pseudoxanthoma elasticum manifestations. Therefore, the dermatologist should provide the patient with the best therapeutical and preventive approaches.

Pseudoxanthoma elasticum: a rare case report

&lt;p class="abstract"&gt;Pseudoxanthoma elasticum (PXE) is a hereditary systemic connective tissue disease affecting mainly the skin, retina and cardiovascular system. Pathologically, it is characterized by mineralization and fragmentation of elastic fibers (so-called "elastorhexia"). PXE is associated with mutations in the ABCC6 (ATP binding cassette subtype C number 6) gene. Women are affected more than men. A 22-year-old woman came to our department with complaints of small, yellowish raised lesions in rows or lacy pattern on her neck since 2 years, some of which coalesced to form larger lesions. She also complains that the skin has been soft, flabby, and wrinkled since 2 years in the armpits, trunk, groin, and knees. On examination, the lesions were slightly pebbly in appearance; such papular lesions tend to coalesce gradually to form plaques with a cobblestone appearance. On histopathological examination, elastic fibers appear basophilic due to calcium deposition. The fibers were fragmented, swollen, and clustered in the middle and deep reticular dermis. The collagen fibers were split. Based on the above findings, a diagnosis of PXE was made. Due to the rarity of the disease, we are reporting this case. The course and prognosis were explained to the patient. Most of the pathological changes associated with PXE are irreversible, but prophylactic measures can be taken to minimize the course of the disease.&lt;/p&gt;

Heterogenous improvements in endothelial function by sub-blood pressure lowering doses of ARBs result in major anti-aortic root remodeling effects

Low basal nitric oxide (NO) production is associated with a dysfunctional endothelium and vascular diseases. We have shown that some angiotensin II (AngII) receptor type 1 (AT1R) blockers (ARBs), a group of clinic-approved blood pressure (BP)-lowering medications, are also capable of activating endothelial function acutely and chronically, both ex vivo and in vivo, in pleiotropic, AngII-independent fashions, which suggested that endothelial function enhancement with ARBs may be independent of their well-documented BP lowering properties. Herein, we attempt to identify the most potent ARB at activating endothelial function when administered at sub-BP-lowering doses and determine its anti-aortic root remodeling properties in a model of Marfan syndrome (MFS). Amongst the 8 clinically available ARBs tested, only telmisartan and azilsartan induced significant (70% and 49%, respectively) NO-dependent inhibition of aortic contractility when administered for 4 weeks at sub-BP lowering, EC5 doses. Low-dose telmisartan (0.47 mg/kg) attenuated MFS-associated aortic root widening, medial thickening, and elastic fiber fragmentation to the same degree as high-dose telmisartan (10 mg/kg) despite wide differences in BP lowering between the two doses. Our study suggests that telmisartan is the most potent ARB at promoting increased endothelial function at low sub-BP doses and that it retained major aortic root widening inhibition activities. ARBs may enhance endothelial function independently from BP-lowering pathways, which could lead to new therapeutic approaches.

ASCENDING AORTIC ANEURYSMS: SURGERY, RMODELLING & AI

ASCENDING AORTIC ANEURYSMS: SURGERY, RMODELLING & AI

Tumor Microenvironment in Oral Squamous Cell Carcinoma: Special Stains and Scanning Electron Microscopic Study.

Effect of the oral cancerous epithelial cells on the extracellular matrix (ECM) and vice versa is also responsible for the growth and progression of cancer. The effect of inflammation on the stroma and its association with progression has also been stated in literature. The control group consisted of 10 patients with apparently normal mucosa with no history of habits, the study group consisted of 30 patients with oral squamous cell carcinoma (OSCC) confirmed by examination and incisional biopsy. H and E staining, Masson's Trichrome Staining, and Verhoeff's Van Gieson staining were used to study the inflammation, collagen fibers, and elastic fiber, respectively. A few selected specimens were studied under the scanning electron microscope. The grade of inflammation was statistically correlated with collagen and elastic fibers. Grade of inflammation was closely associated with lymphadenopathy and the density of collagenous and elastic components of the ECM. The scanning electron microscopic evaluation of elastic fibers revealed irregular fragmented elastic fibers. The stroma is the key to complete removal and treatment of OSCC; however, more studies are needed to define the role of each component, therefore improving the prognosis of a patient.

Allopurinol blocks aortic aneurysm in a mouse model of Marfan syndrome via reducing aortic oxidative stress.

Increasing evidence indicates that redox stress participates in MFS aortopathy, though its mechanistic contribution is little known. We reported elevated reactive oxygen species (ROS) formation and NADPH oxidase NOX4 upregulation in MFS patients and mouse aortae. Here we address the contribution of xanthine oxidoreductase (XOR), which catabolizes purines into uric acid and ROS in MFS aortopathy. In aortic samples from MFS patients, XOR protein expression, revealed by immunohistochemistry, increased in both the tunicae intima and media of the dilated zone. In MFS mice (Fbn1C1041G/+), aortic XOR mRNA transcripts and enzymatic activity of the oxidase form (XO) were augmented in the aorta of 3-month-old mice but not in older animals. The administration of the XOR inhibitor allopurinol (ALO) halted the progression of aortic root aneurysm in MFS mice. ALO administrated before the onset of the aneurysm prevented its subsequent development. ALO also inhibited MFS-associated endothelial dysfunction as well as elastic fiber fragmentation, nuclear translocation of pNRF2 and increased 3'-nitrotyrosine levels, and collagen maturation remodeling, all occurring in the tunica media. ALO reduced the MFS-associated large aortic production of H2O2, and NOX4 and MMP2 transcriptional overexpression. Allopurinol interferes in aortic aneurysm progression acting as a potent antioxidant. This study strengthens the concept that redox stress is an important determinant of aortic aneurysm formation and progression in MFS and warrants the evaluation of ALO therapy in MFS patients.

Stochastic modeling of inhomogeneities in the aortic wall and uncertainty quantification using a Bayesian encoder–decoder surrogate

Inhomogeneities in the aortic wall can lead to localized stress accumulations, possibly initiating dissection. In many cases, a dissection results from pathological changes such as fragmentation or loss of elastic fibers. But it has been shown that even the healthy aortic wall has an inherent heterogeneous microstructure. Some parts of the aorta are particularly susceptible to the development of inhomogeneities due to pathological changes, however, the distribution in the aortic wall and the spatial extent, such as size, shape and type, are difficult to predict. Motivated by this observation, we describe the heterogeneous distribution of elastic fiber degradation in the dissected aortic wall using a stochastic constitutive model. For this purpose, random field realizations, which model the stochastic distribution of degraded elastic fibers, are generated over a non-equidistant grid. The random field then serves as input for a uniaxial extension test of the pathological aortic wall, solved with the finite element method. To include the microstructure of the dissected aortic wall, a constitutive model developed in a previous study is applied, which also includes an approach to model the degradation of interlamellar elastic fibers. To then assess the uncertainty in the output stress distribution due to the proposed stochastic constitutive model, a convolutional neural network, specifically a Bayesian encoder–decoder, was used as a surrogate model that maps the random input fields to the output stress distribution obtained from the finite element analysis. The results show that the neural network is able to predict the stress distribution of the finite element analysis while also significantly reducing the computational time. In addition, this provides the probability for exceeding certain rupture stresses within the aortic wall, which could allow for the prediction of delamination or fatal rupture.

Pentagalloyl Glucose (PGG) Prevents and Restores Mechanical Changes Caused by Elastic Fiber Fragmentation in the Mouse Ascending Aorta.

Thoracic aortic aneurysm (TAA) is characterized by dilation of the aorta that can lead to dissection or rupture. Degradation of elastic fibers is a consistent histopathological feature of TAA that likely contributes to disease progression. Pentagalloyl glucose (PGG) shows promise for stabilizing elastic fibers in abdominal aortic aneurysms, but its efficacy and mechanical effects in the thoracic aorta are unknown. We simulated TAAs using elastase (ELA) to degrade elastic fibers in the mouse ascending aorta and determined the preventative and restorative potential of PGG. Biaxial mechanical tests, constitutive model fitting, and multiphoton imaging were performed on untreated (UNT), PGG, ELA, PGG + ELA, and ELA + PGG treated aortas. PGG treatment alone does not significantly alter mechanical properties or wall structure compared to UNT. ELA treatment alone causes an increase in the unloaded diameter and length, decreased compliance, significant changes in the material constants, and separation of the outer layers of the aortic wall compared to UNT. PGG treatment before or after ELA ameliorates the mechanical and structural changes associated with elastic fiber degradation, with preventative PGG treatment being most effective. These results suggest that PGG is a potential pharmaceutical option to stabilize elastic fibers in TAA.

Structural abnormalities in the non-dilated ascending aortic wall of bicuspid aortic valve patients

BackgroundA bicuspid aortic valve (BAV) is the most common congenital cardiac malformation. The development of the aortic valve is closely related to the development of the ascending aorta, associated with structural differences in the bicuspid aorta. Here we describe the non-dilated ascending aortic wall in bicuspid aortic valve patients. MethodsBAV (n=41) and tricuspid aortic valve (TAV) (n=18) non-dilated ascending aortic wall samples were studied. We investigated the following features of the aortic wall: vessel wall thickness, endothelial cell morphology, atherosclerosis, and elastic lamellae organization. Medial pathologic features encompassing elastic fiber thinning, fragmentation and degeneration, overall medial degeneration, mucoid extracellular matrix accumulation, and smooth muscle cell nuclei loss were studied. Furthermore, we included apoptosis, periaortic inflammation, and the level of expression of differentiated vascular smooth muscle cells. ResultsThe non-dilated BAV ascending aortic wall is characterized by a significantly thinner intimal layer, without features of atherosclerosis (P<.001). The medial layer is significantly thicker (P<.001) with more mucoid extracellular matrix accumulation (P<.001). All other medial pathologic features were more prominent in the TAV (P<.001). The media has significantly less differentiated vascular smooth muscle cells (P<.001) between the neatly regulated elastic lamellae which are thinner in the BAV as compared to the TAV (P<.0001). ConclusionsThe BAV ascending aorta without dilatation is characterized by a differentiation defect of vascular smooth muscle cells in the media and a significantly thinner intimal layer without overt pathologic features.

Histological difference in ligament flavum between degenerative lumbar canal stenosis and non-stenotic group: A prospective, comparative study.

BACKGROUNDLigament flavum (LF) hypertropy is the main etiopathogenesis of lumbar canal stenosis (LCS). The purely elastic LF undergoes a morphological adaptation including a reduction in the elastic fibers and a consequent increase in the collagen content, fibrosis, cicatrization, and calcification. However, the morphometric analysis can delineate the LF in patients with LCS from those without LCS, which would help in better understanding LCS pathogenesis.AIMTo compare the histopathological changes in LF between the degenerative LCS and non-stenotic (non-LCS) group.METHODSThe present prospective study was conducted in 82 patients who were divided into two groups, namely LCS and non-LCS. Demographic details of the patients such as duration of symptoms, level of involvement, and number of segments were recorded. The LF obtained from both groups was histopathologically examined for the fibrosis score, elastic fiber degeneration, calcification, and chondroid metaplasia. Morphometrical details included a change in elastin and collagen percentages, elastin/collagen ratio, elastic fiber fragmentation, and ligamentocyte numbers. All parameters were compared between the two groups by using the independent t test, Chi-square test, and Pearson’s correlation test.RESULTSOut of 82 cases, 74 were analysed, 34 in LCS and 40 in non-LCS group. The mean ± SD age of presentation in LCS and non- LCS group was 49.2 ± 8.9 and 43.1 ± 14.3 respectively. The LCS group (n = 34) exhibited significant differences in fibrosis (P = 0.002), elastic fiber degeneration (P = 0.01), % elastic fragmentation (66.5 ± 16.3 vs 29.5 ± 16.9), % elastic, content (26.9 ± 6.7 vs 34.7 ± 8.4), % collagen content (63.6 ± 10.4 vs 54.9 ± 6.4), reduction of elastic/collagen (0.4 ± 0.1 vs 0.6 ± 0.1), and ligamentocyte number (39.1 ± 19.1 vs 53.5 ± 26.9) as compared to non-LCS group (n = 40). The calcification (P = 0.08) and Pearson’s correlation between duration and loss of elastin was not significant. The difference in LF morphology is consistent in patient’s ≥ 40 years of age among the groups as found in subgroup analysis. Similarly in the patents < 40 and > 40 in the non-LCS group.CONCLUSIONLF is vital in the pathogenesis of LCS. The purely elastic LF undergoes a morphological adaptation that includes a reduction in the elastic fibers with a consequent increase in the collagen content, fibrosis, cicatrization, and calcification. The present study provides a detailed morphometric analysis to semiquantitatively delineate the LF changes in patients with LCS from those in patients without LCS.

Comparison of microanatomy of ascending aorta and pulmonary trunk with age: A cross-sectional study

Cardiovascular disease (CVD) accounts for the leading cause of mortality worldwide and it has a strong association with age. Aging brings about structural and functional changes in vessels, culminating in CVD. This study aims at determining and comparing the structural age changes in the two great vessels of heart, ascending aorta (AA) and pulmonary trunk (PT).Human ascending aorta and pulmonary trunk samples were obtained during autopsy from 55 individuals of different age group. After processing, they were stained with eosin haematoxylin and special stains to identify connective tissue fibres and smooth muscle cells. Thickness of each tunic of the vessel wall, full wall thickness, quantity of smooth muscle cells and severity of fragmentation of elastic fibres were detected.In all age groups, PT was thinner than AA. Average full wall thickness of AA was greatest in the sixth decade of life while that of PT in the fourth decade. Elastic fibres were long, straight and arranged in a lamellar pattern in tunica media of both the vessels in fetal life. They underwent fragmentation from first decade of life in PT and from third decade in AA. Grade5 fragmentation was noticed only in PT. Degeneration of smooth muscle cells occurred in both the vessels with age, but was very little in PT.Both the great vessels showed degenerative changes with advancing age, but after the first decade of life, the changes were very less in PT when compared to AA.

Elastin integrity in bicuspid valve-associated aortopathy is associated with altered biomechanical properties and influenced by age.

BackgroundAortic wall remodelling in bicuspid aortic valve (BAV) patients is heterogeneous and characterized by elastin fiber breakdown alongside impaired biomechanics. However, the relationship between aortic histopathological changes and biomechanics are incompletely understood. We clarify the influence of elastin fiber integrity on ex vivo aortic wall mechanical properties in BAV patients, and explore the influence of patient age.MethodsAortic tissue samples (N=66) from 19 BAV patients undergoing prophylactic ascending aortic resection surgery were analyzed. Semi-quantitative histopathological analysis was conducted to assess elastin fiber integrity including elastin content and elastic fiber fragmentation. Ex vivo biaxial mechanical testing generated stress-strain curves from which physiological [low-strain tangential modulus (LTM), transition zone onset stress (TZo)] and supraphysiological [transition zone end stress (TZe) and high-strain tangential modulus (HTM)] mechanical properties were obtained. Relationships between histopathology and mechanical properties were determined using a linear mixed effect model. BAV patients were subdivided according to ‘younger’ and ‘older’ age groups (i.e., 51–60 and 61–70 years old, respectively).ResultsNo statistically significant differences in elastin content were observed between younger and older BAV patients. Older patients showed greater elastin fiber fragmentation compared to their younger cohort (74% versus 61%). Elastin fiber histopathology was associated with differences in physiological mechanical properties: elastin fragmentation corresponded with lower LTM (P=0.005) and TZo (P=0.044) in younger BAV patients and higher LTM (P=0.049) and TZo (P=0.001) in older BAV patients. Histopathology changes were significantly associated with supraphysiological mechanical properties only in older BAV patients: decreased elastin integrity was associated with increased TZe (P=0.049) and HTM (P<0.001).ConclusionsElastin histopathologic changes in BAV aortopathy correspond with differences in mechanical properties and this relationship is influenced by patient age. These novel findings provide additional mechanistic insights into aortic wall remodeling and support a more nuanced stratification of BAV patients by age.