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At least 109 records · Page 6Linked to original sources
PubMed2006

Aortic stiffness correlates with an increased extracellular matrix turnover in patients with dilated cardiomyopathy.

BACKGROUND: An increased extracellular matrix (ECM) turnover has been associated with poor survival in patients with chronic heart failure (CHF) due to dilated cardiomyopathy (DCM). However, the influence of the accelerated collagen turnover on the progressive large artery stiffening process characterizing CHF has not been clarified. This is relevant because aortic stiffening imposes an additional systolic load and impairs exercise tolerance in CHF patients. Therefore, we investigated whether the serum aminoterminal propeptide of type III collagen (PIIINP), an established marker of ECM turnover and tissue fibrosis in DCM, was associated with aortic stiffness in DCM patients. METHODS AND RESULTS: A total of 89 patients with clinical diagnosis of DCM (age 62 +/- 9 years, 80% men, mean ejection fraction 34% +/- 8%) were selected. Aortic pulse-wave velocity (PWV), a well-established marker of aortic stiffness, was measured by Doppler ultrasonography. Serum concentration of PIIINP was determined by radioimmunoassay. Mean aortic PWV was 5.7 +/- 2.3 m/s, and PIIINP was 5.0 +/- 1.3 microg/L. The variables correlated with aortic PWV were age (r = 0.33, P = .002), PIIINP (r = 0.30, P = .005), heart rate (r = 0.27, P = .02), stroke volume (r = -0.24, P = .03) and New York Heart Association class (r = 0.25, P = .02). In a multivariate analysis, age (P = .02) and PIIINP (P = .01) were independently related with aortic PWV, accounting for 27% of its variance. CONCLUSIONS: Higher serum PIIINP levels are independently associated with a stiffer aorta in DCM patients. This suggests that abnormalities in the ECM turnover might involve the proximal elastic vasculature and could partially explain the progressive large artery stiffening process characterizing CHF.

Aged↗
PubMed2006

Microstructural modeling of collagen network mechanics and interactions with the proteoglycan gel in articular cartilage.

Cartilage matrix mechanical function is largely determined by interactions between the collagen fibrillar network and the proteoglycan gel. Although the molecular physics of these matrix constituents have been characterized and modern imaging methods are capable of localized measurement of molecular densities and orientation distributions, theoretical tools for using this information for prediction of cartilage mechanical behavior are lacking. We introduce a means to model collagen network contributions to cartilage mechanics based upon accessible microstructural information (fibril density and orientation distributions) and which self-consistently follows changes in microstructural geometry with matrix deformations. The interplay between the molecular physics of the collagen network and the proteoglycan gel is scaled up to determine matrix material properties, with features such as collagen fibril pre-stress in free-swelling cartilage emerging naturally and without introduction of ad hoc parameters. Methods are developed for theoretical treatment of the collagen network as a continuum-like distribution of fibrils, such that mechanical analysis of the network may be simplified by consideration of the spherical harmonic components of functions of the fibril orientation, strain, and stress distributions. Expressions for the collagen network contributions to matrix stress and stiffness tensors are derived, illustrating that only spherical harmonic components of orders 0 and 2 contribute to the stress, while orders 0, 2, and 4 contribute to the stiffness. Depth- and compression-dependent equilibrium mechanical properties of cartilage matrix are modeled, and advantages of the approach are illustrated by exploration of orientation and strain distributions of collagen fibrils in compressed cartilage. Results highlight collagen-proteoglycan interactions, especially for very small physiological strains where experimental data are relatively sparse. These methods for determining matrix mechanical properties from measurable quantities at the microscale (composition, structure, and molecular physics) may be useful for investigating cartilage structure-function relationships relevant to load-bearing, injury, and repair.

Biomechanical Phenomena↗
PubMed2004

Matrix metalloproteinase-9 genotype influences large artery stiffness through effects on aortic gene and protein expression.

OBJECTIVE: Because large artery stiffening contributes to myocardial ischemia, its determinants are of relevance as potential risk markers. This study examined whether matrix metalloproteinase (MMP)-9 (gelatinase B) genotype is associated with large artery stiffening and aortic MMP-9 gene and protein expression. METHODS AND RESULTS: MMP-9 genotype (C-1562T promoter polymorphism) was determined in 84 patients (73 male) with angiographically defined coronary artery disease (CAD). Carotid applanation tonometry was used to assess central blood pressures and, with Doppler velocimetry, to assess aortic stiffness (input and characteristic impedance). Gene expression real-time polymerase chain reaction (RT-PCR) and protein levels (Western blotting) were assessed in relation to genotype in aortic samples from a separate population. T-allele carriers (C/T and T/T) had stiffer large arteries (higher input and characteristic impedance) and higher carotid pulse and systolic blood pressure (all P<0.05) than C/C homozygotes. In aortic samples, gene expression was 5-fold higher and active protein levels were >2-fold higher in T-allele carriers. CONCLUSIONS: Because the T allele was associated with greater MMP-9 mRNA and protein levels, the greater large artery stiffness in T-allele carriers may be secondary to excessive degradation of the arterial elastic matrix. The consequent higher pulse pressure may increase susceptibility to myocardial ischemia.

Adult↗
PubMed2004

Bipolar and monopolar radiofrequency treatment of osteoarthritic knee articular cartilage: acute and temporal effects on cartilage compressive stiffness, permeability, cell synthesis, and extracellular matrix composition.

The cellular, biochemical, biomechanical, and histologic effects of radiofrequency-generated heat on osteoarthritic cartilage were assessed. Articular cartilage explants (n=240) from 26 patients undergoing total knee arthroplasty were divided based on Outerbridge grade (I or II/III) and randomly assigned to receive no treatment (controls) or monopolar or bipolar radiofrequency at 15 or 30 W. Both potentially beneficial and harmful effects of radiofrequency treatment of articular cartilage were noted. It will be vital to correlate data from in vitro and in vivo study of radiofrequency thermal chondroplasty to determine the clinical usefulness of this technique.

Biomechanical Phenomena↗
PubMed1990

New design of hip prosthesis using carbon fibre reinforced composite.

We present a new design for a hip prosthesis using polyethylene-hydroxyapatite, a composite material with layered stiffness and good bone compatibility. In order to overcome the low stiffness of the matrix, carbon fibre reinforcement is suggested. This new collarless prosthesis was designed to give maximum stiffness at the core and lower stiffness at the bone-implant interface. For this design a 2D finite element analysis was undertaken; its results were compared with those for a titanium alloy prosthesis. The effect of the variation in the collar stiffness was also analysed.

Carbon↗
PubMed2006

Pathophysiology, genetic, and therapy of arterial stiffness.

Stiffening of large arteries is considered as an independent predictor of cardiovascular events. This article summarizes recent theories on the mechanisms contributing to arterial stiffness involving extracellular matrix proteins, endothelial and smooth muscle cells, cell-matrix interactions, and genetic background. Despite the important role of genetic factors in essential hypertension, little is known about the genetic of arterial stiffness. In the future, candidate genes approaches will allow to determine the cellular and molecular mechanisms of arterial stiffness. A review of different strategies aimed at lowering arterial stiffness and potentially reducing cardiovascular risk are presented. Lifestyle changes and antihypertensive drugs have showed beneficial effects in reversing stiffness. New emerging tools as gene therapy and molecules involved in matrix attachments or crosslink of collagen may be promising. Therapeutic trials using such strategies will be necessary to demonstrate their impact on morbidity and mortality.

Animals↗
PubMed2005

Cell tension, matrix mechanics, and cancer development.

Oncologists often diagnose cancer based on a change of tissue stiffness sensed by palpation, yet cancer researchers generally focus on biochemical signaling mechanisms. Tumors are more rigid because they have a stiffer extracellular matrix. A new study shows that this alteration of matrix mechanics activates integrins, which not only promotes mitogenic signaling through Erk but also cell contractility through Rho, which can further increase matrix stiffness. This establishes a positive feedback loop that switches on the malignant phenotype in mammary epithelial cells. This mechanical "autocrine loop" brings solid-state mechanotransduction on a par with oncogenic signaling pathways in malignant transformation.

Cell Shape↗
PubMed2001

Extreme damping in composite materials with a negative stiffness phase.

Composites with negative stiffness inclusions in a viscoelastic matrix are shown to have higher stiffness and mechanical damping tandelta than that of either constituent and exceeding conventional bounds. The causal mechanism is a greater deformation in and near the inclusions than the composite as a whole. Though a block of negative stiffness is unstable, negative stiffness inclusions in a composite can be stabilized by the surrounding matrix. Such inclusions may be made from single domains of ferroelastic material below its phase transition temperature or from prebuckled lumped elements.

Journal Article↗
PubMed1988

Composition of the cement line and its possible mechanical role as a local interface in human compact bone.

Human compact bone may be viewed as a fiber reinforced composite material in which the secondary osteons act as the fiber reinforcements. The cement line, which is the interface between the 'fibers' (osteons) and extraosteonal bone matrix, may impart important mechanical properties to compact bone. The nature of these properties is not known partly because the composition of the cement line is unknown. This analysis examines the constituents of the osteon cement line using scanning electron microscopy and X-ray microprobe analysis to address its biomechanical functions as a local interface. The analysis suggests that the cement line is a region of reduced mineralization which may contain sulfated mucosubstances. This composition is consistent with the hypothesis that the cement line provides a relatively ductile interface with surrounding bone matrix, and that it provides the point specific stiffness differences, poor 'fiber'-matrix bonding and energy transfer qualities required to promote crack initiation but slow crack growth in compact bone.

Adult↗
PubMed1998

Effect of exercise training on passive stiffness in locomotor skeletal muscle: role of extracellular matrix.

The purpose of this study was to evaluate the effect of endurance exercise training on both locomotor skeletal muscle collagen characteristics and passive stiffness properties in the young adult and old rat. Young (3-mo-old) and senescent (23-mo-old) male Fischer 344 rats were randomly assigned to either a control or exercise training group [young control (YC), old control (OC), young trained (YT), old trained (OT)]. Exercise training consisted of treadmill running at approximately 70% of maximal oxygen consumption (45 min/day, 5 days/wk, for 10 wk). Passive stiffness (stress/strain) of the soleus (Sol) muscle from all four groups was subsequently measured in vitro at 26 degreesC. Stiffness was significantly greater for Sol muscles in OC rats compared with YC rats, but in OT rats exercise training resulted in muscles with stiffness characteristics not different from those in YC rats. Sol muscle collagen concentration and the level of the nonreducible collagen cross-link hydroxylysylpyridinoline (HP) significantly increased from young adulthood to senescence. Although training had no effect on Sol muscle collagen concentration in either age group, it resulted in a significant reduction in the level of Sol muscle HP in OT rats. In contrast, exercise had no effect on HP in the YT animals. These findings indicate that 10 wk of endurance exercise significantly alter the passive viscoelastic properties of Sol muscle in old but not in young adult rats. The coincidental reduction in the principal collagen cross-link HP also observed in response to training in OT muscle highlights the potential role of collagen in influencing passive muscle viscoelastic properties.

Aging↗
PubMed2006

Variation in the human matrix metalloproteinase-9 gene is associated with arterial stiffness in healthy individuals.

BACKGROUND: Arterial stiffness is an important determinant of cardiovascular risk. Elastin is the main elastic component of the arterial wall and can be degraded by a number of enzymes including serine proteases and matrix metalloproteinases (MMPs). Serum MMP-9 levels correlate with arterial stiffness and predict cardiovascular risk. Polymorphisms in the MMP-9 gene are also associated with large artery function in subjects with coronary artery disease. Therefore, we investigated the influence of known MMP-9 (-1562C>T, R279Q) polymorphisms on arterial stiffness in a large cohort of healthy individuals (n=865). METHODS AND RESULTS: Aortic pulse wave velocity (PWV) and augmentation index were assessed. Supine blood pressure, biochemical markers, MMP-9 levels, and serum elastase activity (SEA) were also determined. Genomic DNA was extracted and genotyping performed. Aortic PWV, serum MMP-9, and SEA were higher in carriers of the rare alleles for the -1562C>T and R279Q polymorphisms. These polymorphisms were also associated with aortic PWV after correction for other confounding factors. Stepwise regression models with known or likely determinants of arterial stiffness revealed that approximately 60% of the variability in aortic PWV was attributable to age, mean arterial pressure, and genetic variants (P<0.001). CONCLUSIONS: We have demonstrated for the first time that aortic stiffness and elastase activity are influenced by MMP-9 gene polymorphisms. This suggests that the genetic variation in this protein may be involved in the process of large artery stiffening.

Adult↗
PubMed2002

Fibroblast contractile force is independent of the stiffness which resists the contraction.

Using a device named the cell force monitor, the contractile force developed by fibroblasts has been studied by measuring the macroscopic contraction of porous collagen-glycosaminoglycan (GAG) matrices over the first 24 h following cell attachment. In this paper, the effect of a variation in the stiffness that resists matrix contraction by cells on the contractile force generated by the cells was determined. Data from these experiments revealed that the contractile force generated by the fibroblasts was independent of the stiffness of the resistance within the range tested (0.7-10.7 N/m). These results suggest that during the time when fibroblasts are attaching to and spreading on collagen-GAG matrices the contractile forces they generate are force limited, not displacement limited. Therefore, the cytoskeletal mechanism of force generation, corresponding with cell elongation, is capable of increasing the displacement of adhesion sites in order to develop the same level of force. Although a detailed understanding of how the passive mechanical signals provided by substrate materials affect cell processes is still unavailable, in vitro modeling of cell-mediated contraction continues to provide useful information.

Animals↗
PubMed2006

Mechanical adaptability of a sponge extracellular matrix: Evidence for cellular control of mesohyl stiffness in Chondrosia reniformis Nardo.

The marine sponge Chondrosia reniformis Nardo consists largely of a collagenous tissue, the mesohyl, which confers a cartilaginous consistency on the whole animal. This investigation was prompted by the incidental observation that, despite a paucity of potentially contractile elements in the mesohyl, intact C. reniformis stiffen noticeably when touched. By measuring the deflection under gravity of beam-shaped tissue samples, it was demonstrated that the flexural stiffness of the mesohyl is altered by treatments that influence cellular activities, including [Ca2+] manipulation, inorganic and organic calcium channel-blockers and cell membrane disrupters, and that it is also sensitive to extracts of C. reniformis tissue that have been repeatedly frozen then thawed. Since the membrane disrupters and tissue extracts cause marked stiffening of mesohyl samples, it is hypothesised that cells in the mesohyl store a stiffening factor and that the physiologically controlled release of this factor is responsible for the touch-induced stiffening of intact animals.

Animals↗
PubMed1997

1H NMR relaxation study of a chitosan-cyclodextrin network.

The results of measurements of longitudinal and transverse proton relaxation times for a chemical network obtained by reacting chitosan with oxidized beta-cyclodextrin (beta-cyclodextrin polyaldehyde) are presented. The network was characterized by a 'two-component' transverse relaxation mechanism relative to structurally different environments experienced by water molecules. Different environments were also indicated by the temperature of the spin-spin relaxation times (T2) studied in the range 4-50 degrees C. Between 4 and 18 degrees C, proton exchange between the matrix and water prevails on the inter- and intra-molecular dipolar interactions of the water confined in the meshes of the network, resulting in a marked change in the slope of T2 with temperature. Stiffness of the matrix and reduced mobility of water in the gel meshes are prerequisites for observing such relaxation phenomena. Possible mechanisms contributing to the activation energy in the case of chitosan-cyclodextrin networks are discussed. The behaviour of the chitosan-cyclodextrin hydrogel is compared with that of a gellan gel.

Carbohydrate Sequence↗
PubMed2003

Chronological age modifies the microscopic remodeling process in viable cardiac tissue after infarction.

To define the impact of age on microscopic structural remodeling after myocardial infarction, the physical properties of infarct scar tissue and viable remote zone tissues in young (3 months) and older adult (18 months) Fischer rats were quantified with the use of high-frequency (50 MHz) high-resolution acoustic microscopy 3 months after coronary artery occlusion. We observed that integrated backscatter increased by 100% in the viable zones of old animals after infarction, but remained relatively unaffected in the same regions of younger animals. Mathematical models of myocardial scattering behavior indicated that a 25% increase in stiffness of the extracellular matrix materials in viable zones likely occurred in the older animals. Alterations in gross tissue collagen content were not responsible for this increased stiffness. These observations are compatible with the hypothesis that progressive age-related changes in the quality of the collagen (e.g., excessive age-related crosslinking) rather than its amount per se may have altered the stiffness of the extracellular matrix of remodeled viable tissue in older animals.

Aging↗
PubMed1992

Cracks emanating from slipping inclusions near a bone-implant interface.

It has been hypothesized that mechanical fracture at the bone-cement-implant interface is the initial cause for loosening of orthopedic implants. Previous investigators have observed cracks to emanate from methacrylate beads, apparently acting as inclusions within the cement. It is believed that the bond between these inclusions and the surrounding matrix breaks prior to emanation of radial cracks from the inclusion. An analytical model is developed for radial cracks emanating from circular inclusions that allow slip along their interface. The solution to the interaction of a single dislocation and a slipping inclusion is used as a Green's Function to model the crack. The Mode I stress intensity factors are calculated for arbitrary orientations of the crack and for varying relative stiffness of the matrix and the inclusion to test feasibility of crack growth.

Bone Cements↗
PubMed2003

Repositioning of cells by mechanotaxis on surfaces with micropatterned Young's modulus.

Adherent cells are strongly influenced by the mechanical aspects of biomaterials, but little is known about the cellular effects of spatial variations in these properties. This work describes a novel method to produce polymeric cell culture surfaces containing micrometer-scale regions of variable stiffness. Substrates made of acrylamide or poly(dimethylsiloxane) were patterned with 100- or 10-microm resolution, respectively. Cells were cultured on fibronectin-coated acrylamide having Young's moduli of 34 kPa and 1.8 kPa, or fibronectin-coated PDMS having moduli of 2.5 MPa and 12 kPa. Over several days, NIH/3T3 cells and bovine pulmonary arterial endothelial cells accumulated preferentially on stiffer regions of substrates. The migration, not proliferation, of cells in response to mechanical patterning (mechanotaxis) was responsible for the accumulation of cells on stiffer regions. Differential remodeling of extracellular matrix protein on stiff versus compliant regions was observed by immunofluorescence staining, and may have been responsible for the observed mechanotaxis. These results suggest that mechanically patterned substrates might provide a general means to study mechanotaxis, and a new approach to patterning cells.

Acrylamide↗
PubMed2004

Phenotypic screening for pharmaceuticals using tissue constructs.

Compounds can be screened for pharmaceutical activity either by detecting interactions with specified target molecules such as receptors or enzymes (molecular screening) or observing effects on the structure or physiological activities of cells or tissues (phenotypic screening). Screening at the molecular level has been greatly enhanced by fluorescence methods. Especially the combination of confocal detection with measurements of the amplitudes and time courses of fluorescence fluctuations have reduced sample volumes to < microliters and have increased throughputs to >100000 compounds per day. Screening at the molecular level, however, does not provide information about the effects of test compounds on cellular functions. Phenotypic screening, although much slower than molecular screening, does provide information about effects on cell or tissue structure or function and therefore can be used to eliminate at an early stage compounds that are toxic or do not produce the desired cellular response. Tissue constructs reconstituted using cells of specified types and defined extracellular matrix components provide test systems for detecting the effects of test compounds on cellular mechanical functions such as the development of contractile force and on cell and matrix structure and stiffness. For example, constructs based on vascular smooth muscle cells provide information about effects on cellular contractile force that can be used to identify agents that control blood pressure. Tissue constructs that mimic skeletal, smooth and heart muscles and connective tissues have been produced and can be used to study mechanical and structural responses to active compounds.

Animals↗