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PubMed1990

Interaction of lipoprotein lipase with subendothelial extracellular matrix.

We have analyzed the binding of lipoprotein lipase (LPL) to the subendothelial extracellular matrix produced by cultured endothelial cells. Binding was linear up to a concentration of 0.5 microgram/ml (10 nM) enzyme used in this study, and equilibrium was achieved after 2 h of incubation with bovine 125I-LPL at 4 degrees C. Heparin and heparan sulfate effectively inhibited the binding of LPL to extracellular-matrix-coated plates; chondroitin sulfate had no effect, while high concentrations of dermatan sulfate or keratan sulfate inhibited binding of LPL to extracellular matrix by only 40%. Basic fibroblast growth factor (bFGF) did not affect LPL binding, while antithrombin-III (AT-III) caused up to a 50% inhibition of enzyme binding to extracellular matrix. alpha-Thrombin. 5.10(-6) M, and its esterolytically inactive derivative, DIP-alpha-thrombin, effectively inhibited binding of LPL to extracellular-matrix-coated plates. alpha-Thrombin was also able to release the extracellular-matrix-bound LPL in an active form. Extracellular-matrix-bound LPL detached into medium containing triolein emulsion and/or serum, and was catalytically active after being released. Extracellular-matrix-bound LPL lost 30% of its activity following incubation at 37 degrees C for 4 h. in contrast to soluble LPL which lost 75% of its activity. It is plausible to conclude from these data that in vivo the subendothelial basement membrane, similarly to extracellular matrix, sequesters and stabilizers LPL secreted into the subendothelial space by non-endothelial cells, and thus may play an important role in determining the route of LPL from its site of synthesis to its site of action.

Animals↗

PubMed1982

Combinatorial process for extracellular matrix influences on gene expression: a hypothesis.

The extracellular matrix (ECM) has a number of influences on gene expression during growth and development. Cellular and tissue interactions among similar and dissimilar cell types result in the production of complex and fascinating extracellular matrices throughout development. This paper presents a hypothesis that will emphasize those examples in which the extracellular matrix mediates de novo gene expression termed "determination" of a unique phenotype. It will be found that a number of gene families within the eucaryotic genome can be preferentially activated during the course of differentiation-specific protein expression. Results from a number of laboratories illustrate that close-range and/or short-range cell-cell interactions invoke preferential differentiation-specific protein synthesis and accumulation during embryogenesis. This discussion will highlight how the extracellular matrix microenvironment of a particular population of cells invokes irreversible, differentiation-specific gene expression. Recent advances in the isolation and characterization of a large number of different extracellular matrix macromolecules (eg various types of collagens, fibronectin, chondronectin, osteonectin, laminin, proteoglycans, enamel protein) now suggest a renewed interest in this problem area, and also the promise for significant breakthroughs in the near future. The combinatorial hypothesis for extracellular matrix influences on gene expression states that changing, rearranging, or altering the macromolecular constituents within ECM results in a myriad diversity in developmental instructions. The hypothesis predicts that no individual morphogen is required.

Cell Communication↗

PubMed1991

Structure and function of the extracellular matrix of anuran eggs.

The extracellular matrix (ECM) surrounding the anuran egg is composed of jelly coat layers, an envelope, and the perivitelline space, which separates the envelope from the egg plasma membrane. Both the jelly coat layers and egg envelopes are required for fertilization in anurans. This paper reviews the current understanding of the structure-function relations of the ECM, with emphasis on the egg envelope. The fibrous egg envelope exists in four related forms. The envelope forms differ in their ultrastructures, macromolecular compositions, and cellular functions. After the oocyte is released from the ovary, conversion of one envelope form to another is brought about by factors secreted by the oviduct prior to fertilization and by factors released from the egg in the sperm-triggered cortical reaction. An additional extracellular matrix structure, located in the perivitelline space, has recently been identified in Xenopus laevis, as well as a previously undescribed reorganization of envelope fibers occurring at fertilization. The molecular changes in the ECM glycoproteins (limited proteolysis, lectin-ligand binding, and conformational changes) and the oviductal and egg macromolecules responsible for the conversion of envelope forms are discussed. New experimental evidence that supports the lectin-ligand hypothesis for the formation of the fertilization layer is presented. It is proposed that the molecular changes in the ECM are responsible for the ultrastructural alterations of the ECM and for modifications of the fertilization and developmental functions of the anuran egg ECM.

Animals↗

PubMed2006

Effects of static and cyclic loading in regulating extracellular matrix synthesis by cardiovascular cells.

Extracellular matrix (ECM) provides several structural and functional characteristics to tissues including cell support, mechanical integrity and biological signaling. In cardiovascular tissues, cells produce various ECM components such as collagen, elastin, proteoglycans, matrix metalloproteinases, growth factors and signaling molecules. The cardiovascular cells (cardiac fibroblasts, cardiomyocytes, endothelial cells, and vascular smooth muscle cells) sense the changes in mechanical strains applied to them, through cell-surface receptors such as integrins and ion channels, and adjust their expression and synthesis of ECM molecules in order to adapt their environment to these changes. ECM changes due to altered mechanics are evident in numerous pathological situations including hypertension, cardiac hypertrophy, myocardial infarction, myxomatous heart valve disease, and atherosclerosis. In hypertrophic conditions, for example, increased mechanical loading is involved with enhanced collagen synthesis, whereas in myxomatous and atherosclerotic conditions reduced mechanical strains are accompanied by an accumulation of proteoglycans. Therefore, investigating the effects of various strain patterns on cardiovascular cells can enhance our understanding of ECM regulation and pathologies. This review focuses on the in vitro modulation of the synthesis of various ECM molecules through static or cyclic stretching of cardiovascular cells.

Animals↗

PubMed1995

Extracellular matrix proteins and leukocyte function.

Extracellular matrix (ECM) proteins profoundly affect physiological functioning at the cellular level. Cell growth and differentiation, as well as cell shape and migration via the cytoskeleton, are all affected by ECM proteins. Leukocyte interactions with matrices have recently become an exciting field of research because a number of different leukocyte functions are significantly affected by their binding to ECM proteins. This may be especially important in inflammatory responses where leukocytes are primed for inflammatory mediator and cytokine production by binding to ECM proteins during extravasation. Because activated leukocytes produce potentially damaging substances, the progress of an inflammatory response can be profoundly affected by the ECM proteins encountered by leukocytes during their migration from within the peripheral circulation to sites of inflammation. This review summarizes recent publications describing components of the ECM that influence leukocyte function, the receptors involved in leukocyte binding to ECM proteins, and focuses on the effects of ECM proteins on the production of inflammatory mediators and cytokines by human peripheral blood leukocytes.

Animals↗

PubMed1995

Involvement of extracellular matrix constituents in breast cancer.

It has recently been established that the extracellular matrix is required for normal functional differentiation of mammary epithelia not only in culture, but also in vivo. The mechanisms by which extracellular matrix affects differentiation, as well as the nature of extracellular matrix constituents which have major impacts on mammary gland function, have only now begun to be dissected. The intricate variety of extracellular matrix-mediated events and the remarkable degree of plasticity of extracellular matrix structure and composition at virtually all times during ontogeny, make such studies difficult. Similarly, during carcinogenesis, the extracellular matrix undergoes gross alterations, the consequences of which are not yet precisely understood. Nevertheless, an increasing amount of data suggests that the extracellular matrix and extracellular matrix-receptors might participate in the control of most, if not all, of the successive stages of breast tumors, from appearance to progression and metastasis.

Animals↗

PubMed1993

Content and turnover of extracellular matrix protein in human "nonspecific" and inflammatory abdominal aortic aneurysms.

Inflammatory aneurysms (IAs) have peculiar macroscopic and histological aspects which make them very different from nonspecific aneurysms (NSAs). These morphological differences seem to be determined by significant modifications of the extracellular matrix. Extracellular matrix protein component concentrations were determined biochemically in infrarenal aortic biopsies from 10 NSAs, five IAs and five non-aneurysmal aortic controls. The concentration of each wall component was expressed in % w/w (relative concentration) and in mg/wall longitudinal cm (absolute concentration) with reference to total protein recovered after hydrolysis and amino acid analysis. The biochemical results were correlated with the histological and ultrastructural features of the specimens. A significant increase in total collagen was observed in the two groups of aneurysms, with respect to the controls (NSA = 285%, IA = 382%). In contrast the 80-90% decrease in the relative concentration of elastin observed in both types of aneurysm was less marked (NSA = 55%, IA = 39%). This fall was not significant when expressed in mg/cm, although elastin derived peptide (EDP) levels in the plasma of these patients was significantly higher than in age-matched controls. The concentration of the soluble collagen fraction appeared significantly higher (Mann-Whitney, p < 0.05) in the IAs with respect to the NSAs, whilst no differences were observed between the two groups regarding the concentration of insoluble elastin and of wall and plasma EDPs. As well as providing evidence of increased elastin turnover, this study emphasises the conspicuous modifications of collagen deposition in the wall of abdominal aortic aneurysms which appeared more marked in the inflammatory group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1978

Ultrastructural identification of collagen and glycosaminoglycans in notochordal extracellular matrix in vivo and in vitro.

Notochordal extracellular matrix consists of a continuous basal lamina, amorphous materials and microfibrils embedded in the ground substance of low electron density. Together they comprise the notochord sheath and are of considerable interest because of their suspected role in early embryonic tissue interactions. The notochord is particularly well-suited to morphological investigation of extracellular matrix because it is one of the few embryonic epithelia which produces ultrastructurally recognizable stroma in vitro without the advantage of a collagenous substratum. Furthermore, these matrix components produced in vitro are morphologically identical to those observed in vivo. The present study used ruthenium red staining to demonstrate that notochordal microfibrils exhibit collagen-like cross-banding patterns both in vivo and in vitro. Collagenase and testicular hyaluronidase digestion studies designed to localize collagen and glycosaminoglycans show a reduction of microfibrillar diameters by 30-35%. Furthermore, these enzyme treatments frequently result in enhanced striations of microfibrils. When cis-hydroxyproline (a proline analog) or beta-aminoproprionitrile (BAPN, a lathyrogenic compound) is added to the culture medium, a similar reduction in microfibrillar diameters is seen. Moreover, increased ruthenium red-positive surface coats and large collagen fibrils are frequently present in BAPN-treated cultures, implying a stimulatory metabolic effect. We conclude that most, if not all, notochordal extracellular matrix components are composed of both collagen and glycosaminoglycans and suggest that the entire extracellular matrix should be considered a macromolecular composite which acts in concert to induce or stabilize developmental interactions.

Aminopropionitrile↗

PubMed2006

Differential cell adhesion to vocal fold extracellular matrix constituents.

The human vocal folds are a complex layering of cells and extracellular matrix. Vocal fold extracellular matrix uniquely contributes to the biomechanical viscoelasticity required for human phonation. We investigated the adhesion of vocal fold stellate cells, a novel cell type first cultured by our laboratory, and fibroblasts to eight vocal fold extracellular matrix components: elastin, decorin, fibronectin, hyaluronic acid, laminin and collagen types I, III and IV. Our data demonstrate that these cells adhere differentially to said substrates at 5 to 120 min. Cells were treated with hyaluronidase and Y-27632, a p160ROCK-specific inhibitor, to test the role of pericellular hyaluronan and Rho-ROCK activation in early and mature adhesion. Reduced adhesion resulted; greater inhibition of fibroblast adhesion was observed. We modulated the fibronectin affinity exhibited by both cell types using Nimesulide, an inhibitor of fibronectin integrin receptors alpha5beta1 and alphavbeta3. Our results are important in understanding vocal fold pathologies, wound healing, scarring, and in developing an accurate organotypic model of the vocal folds.

Cell Adhesion↗

PubMed1990

Modulation of extracellular matrix by angiotensin II: stimulated glycoconjugate synthesis and growth in vascular smooth muscle cells.

A role for angiotensin II (Ang II) in the pathogenesis of hypertension and atherosclerosis was studied using cultured vascular smooth muscle cells from spontaneously hypertensive rats. Chronic exposure of vascular smooth muscle cells, cultured in the presence of 1% plasma-derived serum, to Ang II resulted in a dose-dependent stimulation in growth and incorporation of radiolabeled matrix precursors into extracellular matrix-associated glycoconjugate material. The hormone also stimulated the incorporation of [3H]glycine into extracellular matrix glycoproteins and proteoglycans synthesized by cultures rendered quiescent by maintenance on serum-free medium for 48 h prior to exposure to Ang II. This was negated in the presence of saralasin. In quiescent cultures, a single exposure to angiotensin induced a rapid induction of mRNA coding for the extracellular matrix glycoprotein thrombospondin. Similar results were obtained with cells maintained on medium containing 1% plasma-derived serum; however, the levels of induction were reduced by this procedure. This study demonstrated that Ang II was capable of stimulating both growth and matrix elaboration by cultured vascular smooth muscle cells. These observations are indicative of a pathophysiological role for the vasoconstrictor peptide, which may contribute significantly to the development of hypertension.

Angiotensin II↗

PubMedDate not supplied

Extracellular matrix remodeling and matrix metalloproteinases in the vascular wall during aging and in pathological conditions.

The extracellular matrix provides a structural framework essential for the functional properties of vessel walls. The three dimensional organization of the extracellular matrix molecules - elastin, collagens, proteoglycans and structural glycoproteins - synthesized during fetal development - is optimal for these functions. In uninjured arteries and veins, some proteases are constitutively expressed, but through the control of their activation and/or their inhibition by inhibitors, these proteases have a very low activity and the turn-over of elastic and collagen fibers is low. During aging and during the occurrence of vascular pathologies, the balance between proteases and their inhibitors is temporally destroyed through the induction of matrix metalloproteinase gene expression, the activation of zymogens or the secretion of enzymes by inflammatory cells. Smooth muscle cells, the most numerous cells in vascular walls, have a high ability to respond to injury through their ability to synthesize extracellular matrix molecules and protease inhibitors. However, the three dimensional organization of the newly synthesized extracellular matrix is never functionally optimal. In some other pathologies - aneurysm - the injury overcomes the responsive capacity of smooth muscle cells and the quantity of extracellular matrix decreases. In conclusion, care should be taken to maintain the vascular extracellular matrix reserve and any therapeutic manipulation of the protease/inhibitor balance must be perfectly controlled, because an accumulation of abnormal extracellular matrix may have unforeseen adverse effects.

Aging↗

PubMed1999

Vinculin, Talin, Integrin alpha6beta1 and laminin can serve as components of attachment complex mediating contraction force transmission from cardiomyocytes to extracellular matrix.

Recently, we reported that cardiomyocytes adhere to extracellular matrix at costameres, the striated distribution of vinculin between Z-lines and the sarcolemma, where transmission of contraction forces from myofibrils to the extracellular matrix occurs. To identify other molecules involved in force transmission at costameres, we examined adult rat and embryonic chick cardiomyocytes cultured on coverslips or flexible thin silicone rubber substrata. Immunolocalization of talin showed a costameric, striated distribution, which corresponded to dark contacts with interference reflection microscopy. The molecules involved in substrate adhesion were cross-linked with the non-penetrating cross-linking agent Bis(sulfosuccinimidyl)-suberate and detected by immunohistochemical staining with anti-alpha6, alpha3, alphav, or beta1 integrin antibodies. Both alpha6 and beta1 showed costameric distributions, but alpha3 and alpha(v) did not. The distribution of laminin after cross-linking and extraction also showed a costameric distribution. When anti-integrin beta1 antibody was added to live cardiomyocytes grown on the silicone rubber substratum, the transmission of contraction forces was inhibited. These findings suggest that vinculin, talin, integrin alpha6beta1 and laminin system can be involved in transmission of contraction force to the extracellular matrix.

Animals↗

PubMed1998

Modulation of cell-extracellular matrix interactions.

Changes in extracellular matrix (ECM) structure and composition, such as occur during morphogenesis, can have important regulatory effects on cell behavior. Two fibronectin (FN)-based systems have been developed to dissect how cells respond to different types of ECM. One system mimics the provisional matrix of the wound and is composed of FN cross-linked into a fibrin clot matrix. Unlike cells on FN alone, cells on an FN-fibrin matrix are smaller with cortical distribution of actin filaments and membrane ruffles. Addition of the ECM protein tenascin to the FN-fibrin matrix induces a different cell morphology. Thus, matrix composition can have profound effects on cell phenotype. Cells also interact with FN while assembling it into a fibrillar matrix. Using recombinant FNs, a domain that is required for normal progression of FN fibril formation has been identified. During assembly of this recombinant matrix, formation of actin stress fibers and focal adhesions is delayed, demonstrating that changes in FN matrix structure can affect intracellular organization and activation of signaling pathways.

Actins↗

PubMed2006

Analysis of the interaction of extracellular matrix and phenotype of bladder cancer cells.

BACKGROUND: The extracellular matrix has a major effect upon the malignant properties of bladder cancer cells both in vitro in 3-dimensional culture and in vivo. Comparing gene expression of several bladder cancer cells lines grown under permissive and suppressive conditions in 3-dimensional growth on cancer-derived and normal-derived basement membrane gels respectively and on plastic in conventional tissue culture provides a model system for investigating the interaction of malignancy and extracellular matrix. Understanding how the extracellular matrix affects the phenotype of bladder cancer cells may provide important clues to identify new markers or targets for therapy. METHODS: Five bladder cancer cell lines and one immortalized, but non-tumorigenic, urothelial line were grown on Matrigel, a cancer-derived ECM, on SISgel, a normal-derived ECM, and on plastic, where the only ECM is derived from the cells themselves. The transcriptomes were analyzed on an array of 1186 well-annotated cancer derived cDNAs containing most of the major pathways for malignancy. Hypervariable genes expressing more variability across cell lines than a set expressing technical variability were analyzed further. Expression values were clustered, and to identify genes most likely to represent biological factors, statistically over-represented ontologies and transcriptional regulatory elements were identified. RESULTS: Approximately 400 of the 1186 total genes were expressed 2 SD above background. Approximately 100 genes were hypervariable in cells grown on each ECM, but the pattern was different in each case. A core of 20 were identified as hypervariable under all 3 growth conditions, and 33 were hypervariable on both SISgel and Matrigel, but not on plastic. Clustering of the hypervariable genes showed very different patterns for the same 6 cell types on the different ECM. Even when loss of cell cycle regulation was identified, different genes were involved, depending on the ECM. Under the most permissive conditions of growth where the malignant phenotype was fully expressed, activation of AKT was noted. TGFbeta1 signaling played a major role in the response of bladder cancer cells to ECM. Identification of TREs on genes that clustered together suggested some clustering was driven by specific transcription factors. CONCLUSION: The extracellular matrix on which cancer cells are grown has a major effect on gene expression. A core of 20 malignancy-related genes were not affected by matrix, and 33 were differentially expressed on 3-dimensional culture as opposed to plastic. Other than these genes, the patterns of expression were very different in cells grown on SISgel than on Matrigel or even plastic, supporting the hypothesis that growth of bladder cancer cells on normal matrix suppresses some malignant functions. Unique underlying regulatory networks were driving gene expression and could be identified by the approach outlined here.

Cell Line, Tumor↗

PubMed1995

Regulation of plasminogen activation, matrix metalloproteinases and urokinase-type plasminogen activator-mediated extracellular matrix degradation in human osteosarcoma cell line MG63 by interleukin-1 alpha.

Plasmin-mediated extracellular proteolysis has been implicated in the degradation of bone in normal and pathological conditions. Normal and malignant osteoblasts can produce both tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). We have used the osteosarcoma cell line MG63 to address the question of whether the enhanced bone turnover in osteosarcomas is mediated by t-PA or by u-PAA and to study the effect of the cytokine interleukin-1 alpha (IL-1 alpha), known to influence bone degradation, on the plasminogen activator production and extracellular matrix degradation in malignant osteoblastic cells. Furthermore, the effect of IL-1 alpha on the synthesis of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) was analyzed. u-PA production by MG63 was high (approximately 180 ng/10(6) cells/24 h). Also t-PA and PAI-1 production was observed. u-PA production was rapidly increased in MG63 by IL-1 alpha (10 ng/ml), whereas an effect on t-PA production was only found after a prolonged incubation and hardly any effect of IL-1 alpha on PAI-1 production was observed. mRNA analysis revealed similar effects. u-PA receptor (u-PAR) mRNA was detectable in MG63 cells and could be increased by IL-1 alpha after 24 h. In MG63, u-PA-mediated extracellular matrix degradation was detectable, and IL-1 alpha increased the u-PA-mediated matrix degradation (approximately 2-fold). Under control conditions in MG63, only MMP-2, TIMP-1, and TIMP-2 mRNA could be observed. After the addition of IL-1 alpha, a very rapid increase in MMP-1 and MMP-3 mRNA could be observed as well as a moderate increase in TIMP-1 mRNA. The presence of MMP-2 was demonstrated by gelatin zymography. These results show that IL-1 alpha can stimulate u-PA production and can regulate extracellular proteolytic activity mainly via u-PA induction in the MG63 osteosarcoma cell line. Furthermore, IL-1 alpha has a strong stimulating effect on the production of MMP-1 and MMP-3. These findings suggest that u-PA and possibly MMP-1 and MMP-3 play an important role in the process of bone turnover in osteosarcomas.

Extracellular Matrix↗

PubMed1987

Role of glycosidases in human ovarian carcinoma cell mediated degradation of subendothelial extracellular matrix.

Penetration of the extracellular matrix (ECM) by tumor cells, an event which occurs at various stages of the metastatic process, involves tumor cell glycosidase mediated hydrolysis of proteoglycans (PG). Recently, we observed that human ovarian carcinoma cell lines (HOCC) derived from primary tumors, peritoneal effusions, and distant metastases possess a varying ability to degrade radiolabeled PG of the ECM, while normal cells (human mesothelial cells or ovarian fibroblasts) fail to do so. To determine whether a quantitative relationship exists between glycosidase activity and degradation of ECM, both intracellular and extracellular glycosidase activities were measured for HOCC and normal cell lines. No relationship was found between intracellular glycosidase activities and the ability of cells to degrade ECM. However, a correlation was observed between extracellular or secretory glycosidase activities and HOCC mediated ECM degradation. In particular, a 5-8-fold increase, as compared to normal cells, was observed for HOCC extracellular beta-N-acetylglucosaminidase (EC 3.2.2.30) activity. The accumulation or secretion of this enzyme from HOCC into culture medium was found to be time dependent and not related to intracellular levels. Purified hexosaminidase derived from invasive HOCC was able to hydrolyze [3H]-glucosamine radiolabeled ECM (up to 30% radiolabel) and resulted in the cumulative release of free [3H]-N-acetylglucosamine. This enzyme mediated hydrolysis could be completely prevented with 2-acetamido-2-deoxy-1,5-D-gluconolactone, a competitive inhibitor (Ki 10(-6) M). Finally, HOCC mediated degradation of radiolabeled ECM was discerned to be dependent upon active hexosaminidase action, since tumor cell mediated degradation of ECM could be inhibited by up to 60% in the presence of this synthetic competitive inhibitor. In summary, these studies indicate a strong association between HOCC solubilization of glycoconjugates present in the ECM and extracellular levels of hexosaminidase.

Acetylglucosamine↗

PubMed2006

[Involvement of matrix metalloproteinases in the regulation of myocardial extracellular matrix in patients with congestive heart failure].

OBJECTIVE: To investigate the expression of the matrix metalloproteinases (MMP)-2, -3, and 9, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), fibronectin (FN), and tenascin-C (TN-C) in the myocardium, and their relationship with the myocardial remodeling and heart function in the patients with congestive heart failure (CHF). METHODS: A few tissues of papillary muscles of left ventricle were taken from 39 patients with mitral insufficiency during mitral valve replacement, and from 8 organ donors who had died of accidents to undergo pathological examination and to detect the protein expression of MMP-2, -3, and 9, and TIMP-1 by immunoprecipitation and the expression of FN and TN-C by immunofluorescence test. Peripheral blood samples were collected from these 39 patients and 30 normal controls to examine the plasma MMPs and TIMP-1 by ELISA. RESULTS: Typical myocardial remodeling was seen in the myocardial tissues of the CHF patients. The plasma levels of MMP-2, -3, and -9 of the CHF patients in the cardiac function classes II - IV were all significantly higher than those of the normal controls (P < 0.05 or P < 0.01) with a tendency to increase with the deterioration of heart function, The plasma level of TIMP-1 of the CHF patients in the cardiac function classes II - IV were all significantly higher than that of the normal controls (P < 0.05 or P < 0.01) with a tendency to decrease with the deterioration of heart function. The protein expression levels of MMP-2, -3, and -9 in the myocardium of the CHF patients in the cardiac function classes III - IV were all significantly higher than those of the normal controls (P < 0.05 or P < 0.01) with a tendency to increase with the deterioration of heart function. The protein expression levels of TIMP-1 in the myocardium of the CHF patients in the cardiac function classes III - IV were all significantly lower than that of the normal controls (P < 0.05 or P < 0.01) with a tendency to decrease with the deterioration of heart function. The protein expression levels of FN in the myocardium of the CHF patients in the cardiac function classes II - IV were all significantly lower than that of the normal controls (all P < 0.05) with a tendency to decrease with the deterioration of heart function. The protein expression levels of TN-C in the myocardium of the CHF patients in the cardiac function classes II - IV were all significantly higher than that of the normal controls (all P < 0.01) with a tendency to increase with the deterioration of heart function. CONCLUSION: The increasing expression of MMP-2, -3, and -9 and the decreasing expression of TIMP-1 contribute to the myocardial remodeling, thus changing the extracellular matrix in the myocardium tissue and leading to the development and progression of CHF.

Adult↗

PubMed2003

[Proteolysis directed by the extracellular matrix].

The degradation of extracellular matrix (ECM) during physio-pathological processes involves, essentially, two proteolytic systems: the plasmin (ogen) system and the matrix metalloproteinase (MMP) family. Enzyme activity necessitates the formation of proteolytic cascades acting in the pericellular environment. Several proteins (proteases, integrins, matrix, inhibitors, activators...) participate to enzyme catalysis forming assemblies within specialized plasma membrane structures (invadopodia, caveolae). MMP-mediated ECM degradation leads to the formation of peptides (matricryptins, matrikins) which, in turn, can modulate MMP expression. MMPs (especially gelatinases) can also activate growth factors as pro TGF beta or liberate those factors from matrix sites. Interaction between matrix and gelatinases was shown to influence enzyme activation through several mechanisms. Finally, thrombospondins 1 and 2, matricellular proteins, can regulate gelatinase A by favoring its endocytosis. Those data emphasize the potential interest of certain matrikins or pseudo-matrikins as therapeutic agents to control cell invasion.

Catalysis↗