Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Matrix stiffness”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources
PubMed1999

Temporal regulation of extracellular matrix components in transition from compensatory hypertrophy to decompensatory heart failure.

OBJECTIVE: Extracellular matrix, particularly type I fibrillar collagen, provides tensile strength that allows cardiac muscle to perform systolic and diastolic functions. Collagen is induced during the transition from compensatory hypertrophy to heart failure. We hypothesized that cardiac stiffness during decompensatory hypertrophy is partly due to a decreased elastin:collagen ratio. MATERIALS AND METHODS: We prepared left ventricular tissue homogenates from spontaneously hypertensive rats (SHR) aged 30-36 weeks, which had compensatory hypertrophy with no heart failure, and from SHR aged 70-92 weeks, which had decompensatory hypertrophy with heart failure. Age- and sex-matched Wistar-Kyoto (WKY) rats were used as normotensive controls. In both SHR groups, increased levels of collagen were detected by immuno-blot analysis using type I collagen antibody. Elastin and collagen were quantitated by measuring desmosine/isodesmosine and hydroxyproline spectrophometrically, respectively. To determine whether the decrease in elastin content was due to increased elastinolytic activity of matrix metalloproteinase-2, we performed gelatin and elastin zymography on left ventricular tissue homogenates from control rats, SHR with compensatory hypertrophy and SHR with heart failure. RESULTS: The elastin:collagen ratio was 0.242 +/- 0.008 in hearts from WKY rats. In SHR without heart failure, the ratio was decreased to 0.073 +/- 0.003 and in decompensatory hypertrophy with heart failure, the ratio decreased to 0.012 +/- 0.005. Matrix metalloproteinase-2 activity was increased significantly in SHR with heart failure compared with controls (P < 0.001). The level of tissue inhibitor of metalloproteinase-4 was increased in compensatory hypertrophy and markedly reduced in heart failure. Decorin was strongly reduced in decompensatory heart failure compared with control hearts. CONCLUSIONS: Since collagen was induced in SHR with heart failure, decorin and elastin were decreased and the ratios of gelatinase A and elastase to tissue inhibitor of metalloproteinase-4 were increased, we conclude that heart failure is associated with adverse extracellular matrix remodeling.

Animals↗
PubMed2004

Bending stiffness of a crystalline actin bundle.

The acrosomal process of the sperm of the horseshoe crab (Limulus polyphemus) is a unique crystalline actin bundle, consisting of multiple actin filaments cross-linked by the actin-bundling protein, scruin. For successful fertilization, the acrosomal bundle must penetrate through a 30 microm thick jelly coat surrounding the egg and thus it must be sufficiently stiff. Here, we present two measurements of the bending stiffness of a single crystalline bundle of actin. Results from these measurements indicate that the actin:scruin composite bundle has an average elastic modulus of 2 GPa, which is similar to that of a single actin filament, and a bending stiffness that is more than two orders of magnitude larger than that of a bundle of uncross-linked actin filaments due to stiffening by the scruin matrix.

Acrosome↗
PubMed1996

Determination of chlorzoxazone and 6-hydroxychlorzoxazone in human plasma and urine by high-performance liquid chromatography.

A sensitive and reproducible method is described for the determination of the cytochrome P450 enzyme 2E1 substrate chlorzoxazone and its primary metabolite 6-hydroxychlorzoxazone in human plasma and urine. Plasma or diluted urine were acidified, incubated with beta-glucuronidase and then were extracted with diethyl ether. Separation of the analytes was achieved on a C18 column with UV detection set at 283 nm. Excellent linearity was observed over the concentration ranges of 100-3000 ng/ml and 4-400 micrograms/ml in plasma and urine, respectively. The intra-assay variability was < or = 5.1% and the inter-assay variability was < or = 8.2% for each compound in each matrix. The method presented is applicable to pharmacokinetic and pharmacogenetic studies utilizing chlorzoxazone.

Chlorzoxazone↗
PubMed2002

Fibrillin-1 genotype is associated with aortic stiffness and disease severity in patients with coronary artery disease.

BACKGROUND: Elevated pulse pressure is associated strongly with adverse cardiovascular outcome; however, the genetic basis of this condition is unknown. This study examined whether genotypic variation in the extracellular matrix protein fibrillin-1, the Marfan gene, was associated with aortic stiffening and therefore could contribute to cardiovascular risk associated with pulse pressure elevation in coronary disease. METHODS AND RESULTS: Patients (n=145; 113 men), 62+/-9 years of age (mean+/-SD), with angiographically confirmed coronary disease, were studied. Carotid applanation tonometry was used to assess central blood pressures, and in conjunction with Doppler velocimetry, to assess aortic input and characteristic impedance. Fibrillin-1 genotype was characterized by a variable nucleotide tandem repeat and 2 single-nucleotide polymorphisms. The variable nucleotide tandem repeat was a good predictor of underlying haplotypes with 3 genotypes (2-2, 2-4, and 2-3) accounting for 86% of the population. The 2-3 genotype had higher input impedance (P=0.002), characteristic impedance (P=0.005), and carotid pulse pressure (P=0.002) compared with the 2-2 and 2-4 genotypes. Disease severity assessed by previous angioplasties and the number of patients with a stenosis >90% was also greater in the 2-3 genotype. Furthermore, in a multivariate analysis, fibrillin-1 genotype and central pulse pressure were independent of conventional risk factors in determining coronary disease severity. There was no difference in age, sex ratio, body mass index, smoking status, cholesterol level, or medication among the 3 genotypes. CONCLUSIONS: Although a causative link has not been shown, these data are consistent with an important role for fibrillin-1 genotype in cardiovascular risk associated with large-artery stiffening and pulse pressure elevation in individuals with coronary disease.

Alleles↗
PubMed2001

Chondrocyte deformation within mechanically and enzymatically extracted chondrons compressed in agarose.

Within articular cartilage, the chondron microenvironment will influence chondrocyte behaviour and response to loading. Chondrons were extracted from intact cartilage using either mechanical homogenisation (MC) or enzymatic digestion (EC) and cell and matrix morphology in unstrained and compressed agarose constructs was examined. Isolated chondrocytes (IC) were used for comparison. Immunolocalisation of type VI collagen and keratan sulphate revealed differences in the structure of the pericellular microenvironment such that MC most closely resembled chondrons in situ. The unstrained cell diameters of IC and EC were larger than MC at day 1 and increased significantly over a 7 day culture period. In contrast, cell diameters for MC remained constant. Compression of constructs at day 1 resulted in cell deformation for IC and EC but not MC. The two chondron extraction methods yielded chondrons of differing matrix morphology and associated differences in cell size and cellular response to load. The results indicate that the pericellular microenvironment of MC initially possessed a greater mechanical integrity than that of EC. Although these differences may be reduced with time in culture, characterisation of mechanically isolated chondrons suggests that the stiffness of the chondrons in situ may be greater than previous estimates.

Animals↗
PubMed2000

Biomechanical evaluation of a new bone cement for use in vertebroplasty.

STUDY DESIGN: Comparative ex vivobiomechanical study. OBJECTIVES: To determine the strength and stiffness of osteoporotic vertebral bodies subjected to compression fractures and subsequently stabilized via bipedicular injection of one of two bone cements: one is a commercially available polymethylmethacrylate (Simplex P) and one is a proprietary glass-ceramic-reinforced BisGMA/BisEMA/TEGDMA matrix composite that is being developed for use in vertebroplasty (Orthocomp). SUMMARY OF BACKGROUND DATA: Osteoporotic compression fractures present diagnostic and therapeutic challenges for the clinician. Vertebroplasty, a new technique for treating such fractures, stabilizes vertebral bodies by injection of cement. Little is known, however, about the biomechanics of this treatment. METHODS: Five vertebral bodies (L1-L5) from each of four fresh spines were harvested from female cadavers (age, 80 +/- 5 years), screened for bone density using DEXA (t = -3.4 to -6.4), disarticulated, and compressed in a materials testing machine to determine initial strength and stiffness. The fractures then were repaired using a transpedicular injection of either Orthocomp or Simplex P and recrushed. RESULTS: For both cement treatments, vertebral body strength after injection of cement was significantly greater than initial strength values. Vertebral bodies augmented with Orthocomp recovered their initial stiffness; however, vertebral bodies augmented with Simplex P were significantly less stiff than they were in their initial condition. CONCLUSIONS: Augmentation with Orthocomp results in similar or greater mechanical properties compared with Simplex P, but these biomechanical results have yet to be substantiated in clinical studies.

Aged↗
PubMed2002

Viscoelastic properties of pressure overload hypertrophied myocardium: effect of serine protease treatment.

To determine whether and to what extent one component of the extracellular matrix, fibrillar collagen, contributes causally to abnormalities in viscoelasticity, collagen was acutely degraded by activation of endogenous matrix metalloproteinases (MMPs) with the serine protease plasmin. Papillary muscles were isolated from normal cats and cats with right ventricular pressure overload hypertrophy (POH) induced by pulmonary artery banding. Plasmin treatment caused MMP activation, collagen degradation, decreased the elastic stiffness constant, and decreased the viscosity constant in both normal and POH muscles. Thus, whereas many mechanisms may contribute to the abnormalities in myocardial viscoelasticity in the POH myocardium, changes in fibrillar collagen appear to play a predominant role.

Animals↗
PubMedDate not supplied

Matrix, cytoskeleton, or myofilaments: which one to blame for diastolic left ventricular dysfunction?

During cardiac filling, the relative contribution of distension of interstitial collagen, of distension of cytoskeletal proteins, and of low-grade diastolic cross-bridge cycling in the generation of diastolic left ventricular (LV) pressure remains unclear. In failing myocardium, interstitial collagen deposition and cross-linking are augmented. This increase in collagen deposition is accompanied by expression of a stiffer isoform of titin in the cardiomyocytes. Higher diastolic stiffness of failing myocardium is therefore not necessarily related to increased interstitial collagen content. Moreover, phosporylation of titin by protein kinase A and G, and inhibition of titin-actin interaction by cytosolic calcium allow for dynamic modulation of its diastolic tension generation and could account for acute shifts of myocardial distensibility. Acute shifts of myocardial distensibility, as occur in hypertrophy or in demand ischemia, have usually been attributed to a diastolic resurgence of cross-bridge interaction. In hypertrophied and failing myocardium, the recent demonstrations of diastolic calcium release from the ryanodine receptor, of deficient diastolic calcium removal from the cytosol, and of enhanced myofilamentary calcium sensitivity support residual diastolic cross-bridge interaction. In demand ischemia, the role of calcium overload in the reduction of diastolic LV distensibility is less clear because of correction of the reduced diastolic LV distensibility by quick stretches but not by a calcium desensitizer. Simultaneous imposition in animal models of multiple molecular changes involving interstitial, cytoskeletal, and myofilamentary proteins could elucidate their relative importance for myocardial stiffness and lead to selective correction of diastolic LV dysfunction as a novel mode of heart-failure therapy.

Actin Cytoskeleton↗
PubMed2025

Impact of the ECM on the Mechanical Memory of Cancer Cells.

Besides genomic and proteomic analyses of bulk and individual cancer cells, cancer research focuses on the mechanical analysis of cancers, such as cancer cells. Throughout the oncogenic evolution of cancer, mechanical inputs are stored as epigenetic memory, which ensures versatile coding of malignant characteristics and a quicker response to external environmental influences in comparison to solely mutation-based clonal evolutionary mechanisms. Cancer's mechanical memory is a proposed mechanism for how complex details such as metastatic phenotypes, treatment resistance, and the interaction of cancers with their environment could be stored at multiple levels. The mechanism appears to be similar to the formation of memories in the brain and immune system like epigenetic alterations in individual cells and scattered state changes in groups of cells. Carcinogenesis could therefore be the outcome of physiological multistage feedback mechanisms triggered by specific heritable oncogenic alterations, resulting in a tumor-specific disruption of the integration of the target site/tissue into the overall organism. This review highlights and discusses the impact of the ECM on cancer cells' mechanical memory during their metastatic spread. Additionally, it demonstrates how the emergence of a mechanical memory of cancer can give rise to new degrees of individuality within the host organism, and a connection to the cancer entity is established by discussing a connection to the metastasis cascade. The aim is to identify common mechanical memory mechanisms of different types of cancer. Finally, it is emphasized that efforts to identify the malignant potency of tumors should go way beyond sequencing approaches and include a functional diagnosis of cancer physiology and a dynamic mechanical assessment of cancer cells.

Humans↗
PubMed1991

Response of cortical bone to local controlled release of sodium fluoride: the effect of implant insertion site.

In a previous experiment, sodium fluoride in a biodegradable polymer matrix was introduced into the femoral canal of the rabbit and bone formation was compared with contralateral controls. We noted significant bone formation, but only in the distal third of the periosteal surface of the femur. This experiment was performed to distinguish fluoride-induced periosteal bone formation from that due to the reactive osteogenic changes associated with local injury caused by the process of implantation. A proximal approach on the right leg and a distal approach on the left were used for the insertion of the implants in rabbits. Femurs were removed after 30 days and tested for stiffness and load to failure. The cross-sectional area of mineralized bone was determined at proximal, midshaft, and distal locations. Fluorescent bone tissue growth labels were injected at weekly intervals to measure the rate of new periosteal bone formation. The results were compared with a control group that received sham implants. Results showed no difference between measured properties in right and left femurs in the control group or in those exposed to fluoride. A significant increase was found in the fluoride group in load to failure, along with cross-sectional area of mineralized bone, and periosteal growth rates compared with the control group, but no difference was seen in stiffness. No difference was detected between the response proximally and distally in the fluoride group regardless of the location of insertion. There were no detectable changes in serum fluoride level after implantation of the poly L-lactic acid/sodium fluoride matrix. These results show that fluoride exerts its osteogenic effects equally at proximal, midshaft, and distal regions of diaphyseal bone and is uninfluenced by the site of local injury due to insertion of the implant.

Animals↗
PubMed2006

The relationship between myocardial extracellular matrix remodeling and ventricular function.

Elevations in myocardial stress initiate structural remodeling of the heart in an attempt to normalize the imposed stress. This remodeling consists of cardiomyocyte hypertrophy and changes in the amount of collagen, collagen phenotype and collagen cross-linking. Since fibrillar collagen is a relatively stiff material, a decrease in collagen can result in a more compliant ventricle while an increase in collagen or collagen cross-linking results in a stiffer ventricle. If continued elevations in wall stress exceed the ability of the heart to compensate, then the ventricular wall thickness is disproportionately reduced compared to chamber volume and diastolic and systolic dysfunction ensues. This review describes the structural organization of collagen within the myocardium, discusses its effect on ventricular function and considers whether therapy aimed at reducing fibrosis is efficacious in heart failure. The evidence indicates that chamber stiffness can clearly be affected by alterations in both collagen quantity and quality, with the effect of changes in collagen concentration being modified by the extent of collagen cross-linking. The limited evidence available regarding the effects of collagen on systolic function indicates that pharmacological attempts to reduce interstitial collagen have a negative impact. Accordingly, a shift in treatment strategies directed more specifically at affecting collagen cross-linking, rather than reducing the concentration of collagen, may be warranted in the prevention of the adverse impact of collagen alterations on myocardial remodeling.

Cardiomegaly↗
PubMed2004

Ultrasonic delineation of aortic microstructure: the relative contribution of elastin and collagen to aortic elasticity.

Aortic elasticity is an important factor in hemodynamic health, and compromised aortic compliance affects not only arterial dynamics but also myocardial function. A variety of pathologic processes (e.g., diabetes, Marfan's syndrome, hypertension) can affect aortic elasticity by altering the microstructure and composition of the elastin and collagen fiber networks within the tunica media. Ultrasound tissue characterization techniques can be used to obtain direct measurements of the stiffness coefficients of aorta by measurement of the speed of sound in specific directions. In this study we sought to define the contributions of elastin and collagen to the mechanical properties of aortic media by measuring the magnitude and directional dependence of the speed of sound before and after selective isolation of either the collagen or elastin fiber matrix. Formalin-fixed porcine aortas were sectioned for insonification in the circumferential, longitudinal, or radial direction and examined using high-frequency (50 MHz) ultrasound microscopy. Isolation of the collagen or elastin fiber matrices was accomplished through treatment with NaOH or formic acid, respectively. The results suggest that elastin is the primary contributor to aortic medial stiffness in the unloaded state, and that there is relatively little anisotropy in the speed of sound or stiffness in the aortic wall.

Algorithms↗
PubMed1992

Myocardial collagen matrix remodelling in arterial hypertension.

The cardiac interstitium is composed of non-myocyte cells and a structural fibrillar protein network which plays a dominant role in governing the structure, architecture, and mechanical behaviour of the myocardium. Herein we review the fibrillar collagen network, its various components, and the functions they serve in the normal and structurally remodelled myocardium in arterial hypertension. The heterogeneity in myocardial structure, created by the altered behaviour of non-myocyte cells, particularly cardiac fibroblasts, which are responsible for collagen synthesis or degradation and thereby fibrous tissue accumulation, is a major determinant for the appearance of diastolic dysfunction and ultimately systolic myocardial failure. Regulatory mechanisms related to this fibrous tissue response are reviewed to draw attention to the hitherto neglected role of cardiac fibroblasts in mediating adverse structural remodelling of the myocardium and showing how this can be prevented through the use of pharmacological agents that interfere with the regulation of the myocardial collagen matrix. Several lines of evidence suggest that circulating and tissue renin-angiotensin-aldosterone systems (RAAS) are involved in the structural remodelling of the non-myocyte compartment. These include the cardioprotective effects of angiotensin converting enzyme (ACE) inhibition and aldosterone receptor antagonism that were found to prevent myocardial fibrosis in the rat with renovascular hypertension. In the rat with genetic hypertension, established left ventricular hypertrophy and abnormal myocardial diastolic stiffness due to interstitial fibrosis, RAAS inhibition resulted in restoration of myocardial structure and function to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Patterns of myocardial fibrosis.

The interstitium of the myocardium is composed of predominantly type I collagen; type III collagen is present to a lesser extent. The fibrillar collagens serve as tethers between muscle cells, muscle fibers, and blood vessels while also providing a scaffolding that supports the muscular and vascular compartments. In pressure overload hypertrophy, a continuous structural remodeling of the fibrillar collagen matrix is seen. What is initially an adaptive process that enhances tensile strength can eventuate in pathologic hypertrophy with muscle fiber entrapment, cell loss, and abnormal diastolic and systolic stiffness of the myocardium. Morphologically distinct patterns of myocardial collagen accumulation, or fibrosis, have been identified based on the alignment of thick and thin collagen fibers to one another and to cardiac muscle. Each pattern, representing either a reactive (without necrosis) or reparative process, can alter stiffness in a unique manner. The manner in which the interstitium regulates the nature and proportion of fibrillar collagen formation is unknown and deserving of further study. Such information may lead to the development of antifibrotic agents that counteract, prevent or modify disproportionate collagen remodeling in pressure overload hypertrophy. These agents may thereby ultimately represent corrective forms of therapy for the management of heart failure.

Animals↗
PubMed2001

Oxidative stress and the mechanical properties of naturally occurring chimeric collagen-containing fibers.

The byssal threads of marine mussels are a fiber-reinforced composite material. Fibers are continuous, separated by matrix, and consist of chimeric collagens that encompass within the same primary protein structure domains corresponding to collagen, polyhistidine, and either elastin or dragline spider silk. The elastic modulus (stiffness) of the proximal portion of byssal threads was measured by cyclic stress-strain analysis at 50% extension. Before measurement, the threads were conditioned by various treatments, particularly agitation in aerated or nitrogen-sparged seawater. Stiffness can be permanently increased by more than two times, e.g., from 25 MPa to a maximum of 65 MPa, by simple agitation in aerated seawater. Much but not all of this stiffening can be prevented by agitation under nitrogen. Reversible strain stiffening would seem to be a useful adaptation to lower residual stresses arising from the deformation of two joined materials, i.e., distal and proximal portions with rather different elastic moduli. The permanent strain stiffening that characterizes proximal byssal threads subjected to oxidative stress is probably due to protein cross-linking. In the short term, this results in a stronger thread but at the expense of dynamic interactions between the molecules in the structure.

Animals↗
PubMed1998

Breakers of advanced glycation end products restore large artery properties in experimental diabetes.

Glucose and other reducing sugars react with proteins by a nonenzymatic, posttranslational modification process called nonenzymatic glycation. The formation of advanced glycation end products (AGEs) on connective tissue and matrix components accounts largely for the increase in collagen crosslinking that accompanies normal aging and which occurs at an accelerated rate in diabetes, leading to an increase in arterial stiffness. A new class of AGE crosslink "breakers" reacts with and cleaves these covalent, AGE-derived protein crosslinks. Treatment of rats with streptozotocin-induced diabetes with the AGE-breaker ALT-711 for 1-3 weeks reversed the diabetes-induced increase of large artery stiffness as measured by systemic arterial compliance, aortic impedance, and carotid artery compliance and distensibility. These findings will have considerable implications for the treatment of patients with diabetes-related complications and aging.

Animals↗
PubMed2003

MR imaging of normal and matrix-depleted cartilage: correlation with biomechanical function and biochemical composition.

PURPOSE: To correlate articular cartilage function, as reflected in biomechanical properties and biochemical composition, with magnetic resonance (MR) imaging parameters of normal articular cartilage and cartilage partially depleted of matrix components. MATERIALS AND METHODS: Normal articular cartilage from 12 porcine patellae was evaluated biomechanically, biochemically, and with MR imaging (with and without gadolinium enhancement). The patellae were then enzymatically treated to deplete the matrix of either collagen or proteoglycan and then reevaluated biomechanically, biochemically, and with MR imaging. Correlations between cartilaginous tissue function and MR imaging parameters were made. Analysis of variance was performed to assess the effect of enzymatic treatment on measured parameters. Linear correlations among the MR imaging, biochemical, and biomechanical parameters were performed to determine the strengths of the relationships. P <.05 indicated statistically significant differences. RESULTS: Biochemical, biomechanical, and MR analyses enabled detection of changes caused by matrix depletion (P <.05). T2 was the most useful MR imaging parameter for distinguishing proteoglycan loss from collagen loss. T2 correlated significantly with both biomechanical modulus (indicative of cartilage stiffness; P <.001, R2 = 0.51) and biochemical proteoglycan content (P <.001, R2 = 0.44). Differentiation between proteoglycan loss and collagen loss in terms of T1 improved with gadolinium enhancement. With gadolinium enhancement, proteoglycan depletion was associated with a greater decrease in T1 than collagen depletion (P <.05). CONCLUSION: An association between biochemical and biomechanical functional status and MR imaging parameters of articular cartilage was demonstrated. Linear correlations existed between modulus and proteoglycan content in terms of T2. Additionally, proteoglycan loss and collagen loss had differing effects on gadolinium-enhanced T1 when it was expressed as the ratio of T1 after gadolinium enhancement/T1 before gadolinium enhancement.

Analysis of Variance↗
PubMed1998

Increased compliance in diaphragm muscle of the cardiomyopathic Syrian hamster.

We investigated the hypothesis that diaphragm compliance was abnormal in cardiomyopathic Syrian hamsters (CSH), an experimental model of myopathy. The passive elastic properties of isolated diaphragm muscles were analyzed at both the muscle and sarcomere levels. We used the following passive exponential relationship between stress (sigma) and strain (epsilon): sigma = (Eo/beta) (ebetaepsilon - 1), where Eo is the initial elastic modulus and beta is the stiffness constant. Immunocytochemistry procedures were used to analyze the distribution of two key elastic components of muscle, extracellular collagen and intracellular titin elastic components, as well as the extracellular matrix glycoprotein laminin. Muscle and sarcomere values of beta were nearly twofold lower in CSH (8.7 +/- 1.9 and 8.3 +/- 1.4, respectively) than in control animals (19.7 +/- 1.7 and 16.8 +/- 2.1, respectively) (P < 0.01 for each). Compared with controls, Eo was higher in CSH. Sarcomere slack length was significantly longer in CSH than in control animals (2.1 +/- 0.1 vs. 1.9 +/- 0.1 micrometer, P < 0.05). The surface area of collagen I was significantly larger in CSH (17.4 +/- 1.8%) than in control animals (12.4 +/- 0.7%, P < 0.05). There was no change in the distribution of titin or laminin labelings between the groups. These results demonstrate increased diaphragm compliance in cardiomyopathic hamsters. The increase in CSH diaphragm compliance was observed despite an increase in the surface area of collagen and was not associated with an abnormal distribution of titin or laminin.

Animals↗