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51.
Failure properties of ascending thoracic aortic aneurysms with dysfunctional tricuspid aortic valves
Dimitrios P Sokolis Dimitrios C Angouras 《Interactive Cardiovascular and Thoracic Surgery》2021,33(6):949
Open in a separate windowOBJECTIVESAscending thoracic aortic aneurysms (ATAAs) often coexist with dysfunctional tricuspid aortic valves (TAVs). How valvular pathology relates to the aortic wall mechanical properties requires detailed examination.METHODSIntact-wall and layer-specific mechanical properties from 40 and 21 patients with TAV-ATAAs, respectively, were studied using uniaxial tensile testing, longitudinally and circumferentially. Failure stress (tensile strength), failure stretch (extensibility) and peak elastic modulus (stiffness) measurements, along with histological assays of thickness and elastin/collagen contents, were compared among patients with no valvular pathology (NVP), aortic stenosis (AS) or aortic insufficiency (AI).RESULTSIntact-wall stiffness longitudinally and medial strength and stiffness, in either direction, were significantly lower in AI patients than in AS and NVP patients. Intact-wall/medial thickness and extensibility in either direction were significantly lower in AS patients than in AI and NVP patients. In contrast, intact-wall/medial stiffness circumferentially was significantly higher in AS patients than in NVP patients, consistent with the significantly increased medial collagen in AS patients. Failure properties and medial thickness and elastin/collagen contents were significantly lower (more impaired) in females. The left lateral was the thickest quadrant in NVP patients, but the 4 quadrants were equally thick in AS and AI patients. There were significant differences in strength and stiffness among quadrants, which varied however in the 3 patient groups.CONCLUSIONSThe aortic wall load-bearing capacity was impaired in patients with ATAA in the presence of TAV stenosis or insufficiency. These findings lend biomechanical support to the current guidelines suggesting lower thresholds for elective ascending aorta replacement in cases of aortic valve surgery. 相似文献
52.
The in vitro reactions of nitrite (cured meat preservative) with collagen/elastin produce effects that could cause arterial stiffening, an early marker of essential hypertension. Because dietary cured meat ingestion can be a significant source of human nitrite exposure, the epidemiological association between cured meat consumption and hypertension was studied. We performed a cross-sectional analysis of the third National Health and Nutrition Examination Survey (1988-1994). Hypertension was defined using self-reported history, medication use, and measured blood pressures. A significant age interaction between hypertension and cured meat consumption was noted, and the age group 17 to 40 years was identified as the susceptible group. Cured meat consumption was an independent risk factor in a multivariate regression model that included a large number of covariates. This is the first epidemiological evidence that links cured meat consumption with hypertension. Further work with longitudinal data sets is necessary before recommendations can be considered regarding the proposed hypothesis. 相似文献
53.
颅内动脉瘤是严重威胁人类生命健康的一种.是造成自发性蛛网膜下腔出血的首位原因.该病最大的特点是较高的残死率,即使在现代的医疗条件下颅内动脉瘤破裂出血的死亡率仍高达40%[1]. 相似文献
54.
T J Garrand M L Stetz K M O'Brien G R Gindi L I Laifer L I Deckelbaum 《Lasers in surgery and medicine》1990,10(4):375-383
The difference in fluorescence between normal and atherosclerotic artery has been proposed as a feedback mechanism to guide selective laser ablation of atherosclerotic plaque. This fluorescence difference is due to the relative difference in collagen:elastin content of normal artery and atherosclerotic plaque. However, normal arteries have site-dependent variation in collagen: elastin content which may affect their fluorescence spectra. To evaluate the site dependency of normal arterial fluorescence, helium-cadmium (325 nm) laser-induced fluorescence spectra were analyzed in vitro from the ascending aorta, abdominal aorta, and carotid, femoral, renal, and coronary arteries (N = 57) of 12 normal mongrel dogs. Elastin and collagen contents were determined for a subset of these arteries (N = 15). The spectral width of normal arterial Fluorescence varied by site and correlated with the measured collagen:elastin content at each site (r = -0.84, P less than 0.005). Fluorescence spectra were decomposed into collagen and elastin spectral components by using a linear model with a least-squared error criterion fit. The derived collagen and elastin spectral coefficients correlated with the measured collagen and elastin tissue content (r = 0.75 and 0.83 respectively, P less than 0.005). Thus, the fluorescence spectra of normal arteries is site dependent and correlates with the collagen:elastin content. Therefore, spectral feedback algorithms for laser angioplasty guidance must be site specific. 相似文献
55.
Labat-Robert J 《Ageing research reviews》2004,3(2):233-247
Extracellular matrix (ECM) has been a central topic in aging research for several years. Cell-matrix interactions extend the interest in this topic both for normal tissue homeostatic regulation as well as for its dysregulation in age-related diseases. A relatively new extension of this ever-increasing field of aging research concerns the recognition of the original biological activities exhibited by proteolytic fragments of matrix macromolecules. A number of such matricryptins were recently identified, some of them endowed with harmful effects for tissue function. Some of the breakdown products exert a positive feedback effect by upregulating the biosynthesis of the original macromolecule synthesis and/or the expression of degrading enzymes. This results in vicious circles which might well be involved in tissue aging. The examples detailed in this review concern fibronectin (FN) and elastin. A number of fibronectin fragments (Fn-fr) were shown to exhibit diverse activities including increasing tissue degradation, inflammation and tumor progression. Elastin degradation products acting as agonists on the elastin-laminin receptor can trigger harmful effects such as up-regulation of proteases and free radical production. Both macromolecules are at the center of autoamplifying vicious circles of potential importance for age-dependent modification of tissue function. 相似文献
56.
Summary Cells isolated enzymatically from the aortas of newborn rabbits were aggregated and grown in organ culture. Bundles of microfibrils, some of them with an amorphous core (elastin), were evident in 3-day-old aggregates. Furthermore, droplets of elastin surrounded by darker dots and short filaments, corresponding to the elastic units were observed. In 6-day-old aggregates the number of elastic fibers composed of bundles of microfibrils with deposited elastin increased. Elastic elements which probably resulted from a coalescence of elastic units were also present. These two ways of elastic fiber formation in aggregates are compared with those described in papers on aortic development. 相似文献
57.
Mihir Shah Maria C. Edman Srikanth R. Janga Pu ShiJugal Dhandhukia Siyu LiuStan G. Louie Kathleen RodgersJ. Andrew MacKay Sarah F. Hamm-Alvarez 《Journal of controlled release》2013
Sjögren's syndrome (SjS) is a chronic autoimmune disease characterized initially by lymphocytic infiltration and destruction of exocrine glands, followed by systemic organ damage and B-cell lymphoma. Conventional treatment is based on management of symptoms and there is a shortage of therapies that address the underlying causes of inflammation at source exocrine tissue. The aim of this study was to test a novel protein polymer-based platform consisting of diblock copolymers composed from Elastin-like Polypeptides (ELPs) fused with FKBP12, to deliver a potent immunosuppressant with dose-limiting toxicity, rapamycin (Rapa) also known as Sirolimus, and evaluate its effects on the inflamed lacrimal gland (LG) of non-obese diabetic mouse (NOD), a classic mouse model of SjS. Both soluble and diblock copolymer ELPs were fused to FKBP12 and characterized with respect to purity, hydrodynamic radii, drug entrapment and release. Both formulations showed successful association with Rapa; however, the nanoparticle formulation, FSI, released drug with nearly a 5 fold longer terminal half-life of 62.5 h. The strong interaction of FSI nanoparticles with Rapa was confirmed in vivo by a shift in the monoexponential pharmacokinetic profile for free drug to a biexponential profile for the nanoparticle formulation. When acutely administered by injection into NOD mice via the tail vein, this FSI formulation significantly suppressed lymphocytic infiltration in the LG relative to the control group while reducing toxicity. There was also a significant effect on inflammatory and mammalian target of Rapamycin (mTOR) pathway genes in the LG and surprisingly, our nanoparticle formulation was significantly better at decreasing a proposed tear biomarker of SjS, cathepsin S (CATS) compared to free drug. These findings suggest that FSI is a promising tool for delivering Rapa for treatment of SjS in a murine model and may be further explored to meet the unmet medical challenge of SjS. 相似文献
58.
颅内动脉瘤主要由动脉管壁局部缺陷和管腔内压力增高所致。未破裂的小动脉瘤一般无症状,而破裂动脉瘤则可引起蛛网膜下腔出血(subarachnoid hemorrhage, SAH)。颅内动脉瘤的病因和发病机制迄今尚不完全清楚。大量证据表明,颅内动脉瘤是环境因素与多基因共同作用的复杂性疾病。文章对弹性蛋白(elastin, ELN)和Ⅰ型胶原α2(colagen type Ⅰα2, COL1A2)基因多态性与颅内动脉瘤的联系进行了综述。 相似文献
59.
Maria Delio Kathleen Pope Tao Wang Joy Samanich Chad R. Haldeman‐Englert Paige Kaplan Tamim H. Shaikh Jinlu Cai Robert W. Marion Bernice E. Morrow Melanie Babcock 《American journal of medical genetics. Part A》2013,161(3):527-533
Haploinsufficiency of the elastin gene (ELN) on 7q11.23 is responsible for supravalvular aortic stenosis (SVAS) and other arteriopathies in patients with Williams–Beuren syndrome (WBS). These defects occur with variable penetrance and expressivity, but the basis of this is unknown. To determine whether DNA variations in ELN could serve as genetic modifiers, we sequenced the 33 exons and immediately surrounding sequence of the ELN gene (9,455 bp of sequence) in 49 DNAs from patients with WBS and compared cardiovascular phenotypes. Four missense, and four novel intronic variants were identified from a total of 24 mostly intronic single nucleotide variations and one indel. Two missense changes were present in one patient each, one published, p.Gly610Ser in exon 27 (MAF, 0.003) and one novel, p.Cys714Tyr, in exon 33 (MAF, 0.001), were rare in the general population. To identify a statistical association between the variants identified here and cardiovascular phenotypes a larger cohort would be needed. © 2013 Wiley Periodicals, Inc. 相似文献
60.
目的 检测一个临床诊断为"先天性升主动脉狭窄"家系患者的基因组拷贝数变异,明确其发病的遗传学基础.方法 以一个先天性升主动脉狭窄家系为研究对象,收集患儿及其患病父亲、正常母亲外周血标本,常规提取基因组DNA.应用Affymetrix人类全基因组SNP 6.0芯片对患儿及1例正常健康对照个体进行检测,应用实时定量PCR(real-time quantitative polymerase-chain-reaction,qPCR)方法对芯片分析结果进行验证.结果 经Affymetrix SNP 6.0 芯片分析显示患儿染色体7q11.23区域内弹力蛋白基因(elastin,ELN)5′端大部分及基因上游区域共约80 kb发生杂合性缺失.在ELN基因内设计4对qPCR引物,在家系内进行验证,结果显示ELN的缺失向下游至少累及至第22外显子,且患儿父亲携带与患儿相同的杂合性缺失.结论 ELN 基因部分杂合性缺失为该患儿及其父亲发病的原因,二者之先天异常为主动脉瓣上狭窄(supravalvular aortic stenosis,SVAS).Abstract: Objective To detect the copy number variations(CNVs)in a family with congenital narrowing of the ascending aorta,and to explore the underlying genetic causes of the disease.Methods Peripheral blood samples were collected from an affected boy,his affected father and his apparently normal mother.Genomic DNA Was extracted and genotyped using Affymetrix Genome-Wide Human SNP Array 6.0.CNVs were confirmed by real-time quantitative PCR(qPCR).Results Our SNP Array 6.0analysis showed in the boy an about 80kb heterozygous deletion affecting part of the elastin gene(ELN).Further qPCR assays for four confirmed the presence of the deletion in the boy and his father,and indieated that the deletion involved at least the first 22 ELN exons.Conclusion A heterozygous deletion affecting part of the ELN gene has been identified in the boy and his father, A diagnosis of supravalvular aortic stenosis(SVAS)could he made based on the molecular finding. 相似文献