Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function

2007 ◽  
Vol 87 (4) ◽  
pp. 1285-1342 ◽  
Author(s):  
Francis G. Spinale
Keyword(s):  
Matrix Metalloproteinases ◽  
Cardiac Disease ◽  
Hypertensive Heart Disease ◽  
Matrix Remodeling ◽  
Myocardial Remodeling ◽  
Form And Function ◽  
Disease States ◽  
The Matrix ◽  
And Function ◽  
Remarkable Progress

It is now becoming apparent that dynamic changes occur within the interstitium that directly contribute to adverse myocardial remodeling following myocardial infarction (MI), with hypertensive heart disease and with intrinsic myocardial disease such as cardiomyopathy. Furthermore, a family of matrix proteases, the matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs), has been recognized to play an important role in matrix remodeling in these cardiac disease states. The purpose of this review is fivefold: 1) to examine and redefine the myocardial matrix as a critical and dynamic entity with respect to the remodeling process encountered with MI, hypertension, or cardiomyopathic disease; 2) present the remarkable progress that has been made with respect to MMP/TIMP biology and how it relates to myocardial matrix remodeling; 3) to evaluate critical translational/clinical studies that have provided a cause-effect relationship between alterations in MMP/TIMP regulation and myocardial matrix remodeling; 4) to provide a critical review and analysis of current diagnostic, prognostic, and pharmacological approaches that utilized our basic understanding of MMP/TIMPs in the context of cardiac disease; and 5) most importantly, to dispel the historical belief that the myocardial matrix is a passive structure and supplant this belief that the regulation of matrix protease pathways such as the MMPs and TIMPs will likely yield a new avenue of diagnostic and therapeutic strategies for myocardial remodeling and the progression to heart failure.

scholarly journals Proteolytic Events of Wound-Healing — Coordinated Interactions Among Matrix Metalloproteinases (MMPs), Integrins, and Extracellular Matrix Molecules

2001 ◽  
Vol 12 (5) ◽  
pp. 373-398 ◽  
Author(s):  
Bjorn Steffensen ◽  
Lari Häkkinen ◽  
Hannu Larjava
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Matrix Metalloproteinases ◽  
Wound Repair ◽  
Enzyme Activation ◽  
Processing Enzymes ◽  
The Matrix ◽  
Signaling Receptors ◽  
State Of Rest ◽  
And Function

During wound-healing, cells are required to migrate rapidly into the wound site via a proteolytically generated pathway in the provisional matrix, to produce new extracellular matrix, and, subsequently, to remodel the newly formed tissue matrix during the maturation phase. Two classes of molecules cooperate closely to achieve this goal, namely, the matrix adhesion and signaling receptors, the integrins, and matrix-degrading and -processing enzymes, the matrix metalloproteinases (MMPs). There is now substantial experimental evidence that blocking key molecules of either group will prevent or seriously delay wound-healing. It has been known for some time now that cell adhesion by means of the integrins regulates the expression of MMPs. In addition, certain MMPs can bind to integrins or other receptors on the cell surface involved in enzyme activation, thereby providing a mechanism for localized matrix degradation. By proteolytically modifying the existing matrix molecules, the MMPs can then induce changes in cell behavior and function from a state of rest to migration. During wound repair, the expression of integrins and MMPs is simultaneously up-regulated. This review will focus on those aspects of the extensive knowledge of fibroblast and keratinocyte MMPs and integrins in biological processes that relate to wound-healing.

Differential effects of pressure or volume overload on myocardial MMP levels and inhibitory control

2000 ◽  
Vol 278 (1) ◽  
pp. H151-H161 ◽  
Author(s):  
Yoshitatsu Nagatomo ◽  
Blase A. Carabello ◽  
Mytsi L. Coker ◽  
Paul J. McDermott ◽  
Shintaro Nemoto ◽  
...  
Keyword(s):  
Mitral Regurgitation ◽  
Inhibitory Control ◽  
Species Abundance ◽  
Volume Overload ◽  
Abundance Ratio ◽  
Left Ventricular ◽  
Myocardial Remodeling ◽  
Disease States ◽  
Mmp Inhibitor ◽  
The Matrix

Left ventricular (LV) pressure (PO) or volume (VO) overload is accompanied by myocardial remodeling, but mechanisms that contribute to this progressive remodeling process remain unclear. The matrix metalloproteinases (MMPs) contribute to tissue remodeling in a number of disease states. This study tested the hypothesis that increased MMP expression and activity occur after the induction of an LV overload, which is accompanied by a loss of endogenous MMP inhibitory control. LV MMP zymographic activity and species abundance were measured in dogs under the following conditions: acute PO induced by ascending aortic balloon inflation (6 h, n = 9), prolonged PO by aortic banding (10 days, n = 5), acute VO through mitral regurgitation secondary to chordal rupture (6 h, n = 6), prolonged VO due to mitral regurgitation (14 days, n = 7), and sham controls ( n = 11). MMP zymographic activity in the 92-kDa region, indicative of MMP-9 activity, increased over threefold in acute PO and VO and fell to control levels in prolonged PO and VO. The MMP-9 activity-to-abundance ratio increased by over fourfold with acute VO and twofold in acute PO, suggesting a loss of inhibitory control. Endogenous MMP inhibitor content was unchanged with either PO or VO. Interstitial collagenase (MMP-1) content decreased by 50% with acute VO but not with acute PO. Stromelysin (MMP-3) levels increased by 40% with acute VO and increased by 80% with prolonged PO. Although changes in LV myocardial MMP activity and inhibitory control occurred in both acute and prolonged PO and VO states, these changes were not identical. These results suggest that the type of overload stimulus may selectively influence myocardial MMP activity and expression, which in turn would affect the overall LV myocardial remodeling process in LV overload.

scholarly journals A Tale of Two Proteolytic Machines: Matrix Metalloproteinases and the Ubiquitin–Proteasome System in Pulmonary Fibrosis

2020 ◽  
Vol 21 (11) ◽  
pp. 3878 ◽  
Author(s):  
Willy Roque ◽  
Alexandra Boni ◽  
Jose Martinez-Manzano ◽  
Freddy Romero
Keyword(s):  
Matrix Metalloproteinases ◽  
Pulmonary Fibrosis ◽  
Mesenchymal Cell ◽  
Ubiquitin Proteasome System ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Abnormal Accumulation ◽  
The Matrix ◽  
Intracellular Protein Degradation ◽  
And Function

Pulmonary fibrosis is a chronic and progressive lung disease characterized by the activation of fibroblasts and the irreversible deposition of connective tissue matrices that leads to altered pulmonary architecture and physiology. Multiple factors have been implicated in the pathogenesis of lung fibrosis, including genetic and environmental factors that cause abnormal activation of alveolar epithelial cells, leading to the development of complex profibrotic cascade activation and extracellular matrix (ECM) deposition. One class of proteinases that is thought to be important in the regulation of the ECM are the matrix metalloproteinases (MMPs). MMPs can be up- and down- regulated in idiopathic pulmonary fibrosis (IPF) lungs and their role depends upon their location and function. Furthermore, alterations in the ubiquitin-proteosome system (UPS), a major intracellular protein degradation complex, have been described in aging and IPF lungs. UPS alterations could potentially lead to the abnormal accumulation and deposition of ECM. A better understanding of the specific roles MMPs and UPS play in the pathophysiology of pulmonary fibrosis could potentially drive to the development of novel biomarkers that can be as diagnostic and therapeutic targets. In this review, we describe how MMPs and UPS alter ECM composition in IPF lungs and mouse models of pulmonary fibrosis, thereby influencing the alveolar epithelial and mesenchymal cell behavior. Finally, we discuss recent findings that associate MMPs and UPS interplay with the development of pulmonary fibrosis.

SnoN as a novel negative regulator of TGF-β/Smad signaling: a target for tailoring organ fibrosis

2015 ◽  
Vol 308 (2) ◽  
pp. H75-H82 ◽  
Author(s):  
Matthew R. Zeglinski ◽  
Mark Hnatowich ◽  
Davinder S. Jassal ◽  
Ian M. C. Dixon
Keyword(s):  
Transforming Growth Factor ◽  
Tissue Injury ◽  
Transforming Growth Factor Β ◽  
Negative Regulator ◽  
Matricellular Protein ◽  
Matrix Remodeling ◽  
Structural Support ◽  
The Matrix ◽  
Protein Components ◽  
And Function

Remodeling of the extracellular matrix is beneficial during the acute wound healing stage following tissue injury. In the short term, resident fibroblasts and myofibroblasts regulate the matrix remodeling process through production of matricellular protein components that provide structural support to the damaged tissue. This process is largely governed by the transforming growth factor-β1 (TGF-β1) pathway, a critical mediator of the remodeling process. In the long term, chronic activation of the TGF-β1 pathway promotes excessive synthesis and deposition of matrix proteins, including fibrillar collagens, which ultimately leads to organ failure. SnoN (and its alternatively-spliced isoforms SnoN2, SnoA, and SnoI) is one of four members of a family of negative regulators of TGF-β1 signaling that includes Ski and functional Smad-suppressing elements on chromosomes 15 and 18. SnoN has been shown to be structurally and functionally similar to Ski and has been demonstrated to directly interact with Ski to abrogate gene expression. Despite this, little progress has been made in delineating a specific role for SnoN in the regulation of myofibroblast phenotype and function. This review outlines the current body of knowledge of what we refer to as the “Ski-Sno superfamily,” with a focus on the structural and functional importance of SnoN in mediating the fibrotic response by myofibroblasts following tissue injury.

scholarly journals Biological Aspect of Pathophysiology for Frozen Shoulder

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Chul-Hyun Cho ◽  
Kwang-Soon Song ◽  
Beom-Soo Kim ◽  
Du Hwan Kim ◽  
Yun-Mee Lho
Keyword(s):  
Growth Factors ◽  
Matrix Metalloproteinases ◽  
Immune Cells ◽  
Frozen Shoulder ◽  
Matrix Remodeling ◽  
Biological Aspect ◽  
Novel Treatment ◽  
The Matrix ◽  
Basic Studies

It is fairly well understood that frozen shoulder involves several stages, which reflect the series of process from capsular inflammation and fibrosis to spontaneous resolution of this fibrosis. However, the underlying pathophysiologic process remains poorly determined. For this reason, management of frozen shoulder remains controversial. Determining the pathophysiological processes of frozen shoulder is a pivotal milestone in the development of novel treatment for patients with frozen shoulder. This article reviews what is known to date about the biological pathophysiology of frozen shoulder. Although articles for the pathophysiology of frozen shoulder provide inconsistent and inconclusive results, they have suggested both inflammation and fibrosis mediated by cytokines, growth factors, matrix metalloproteinases, and immune cells. Proinflammatory cytokines and growth factors released from immune cells control the action of fibroblast and matrix remodeling is regulated by the matrix metalloproteinases and their inhibitors. To improve our understanding of the disease continuum, better characterizing the biology of these processes at clearly defined stages will be needed. Further basic studies that use standardized protocols are required to more narrowly identify the role of cytokines, growth factors, matrix metalloproteinases, and immune cells. The results of these studies will provide needed clarity into the control mechanism of the pathogenesis of frozen shoulder and help identify new therapeutic targets for its treatment.

Mechanical Loading and Articular Cartilage Metabolism

2000 ◽  
Author(s):  
Robert Lane Smith
Keyword(s):  
Articular Cartilage ◽  
Matrix Proteins ◽  
Structural Elements ◽  
Post Translational Modification ◽  
Form And Function ◽  
Diarthrodial Joints ◽  
The Matrix ◽  
Cartilage Cells ◽  
Specific Proteins ◽  
And Function

Abstract Articular cartilage provides diarthrodial joints with a loading-bearing surface that ensures functional motility. The physical characteristics of articular cartilage originate with the highly organized matrix of extracellular macromolecules that provide structural elements to the tissue. The matrix specialization rests with specific proteins produced by the cartilage cells, the chondrocytes that undergo extensive post-translational modification through addition of sulfated glycosaminoglycan and oligosaccharides. The matrix proteins fall into three major categories, the collagens, the proteoglycans and the glycoproteins, with each group contributing unique properties to cartilage form and function.

Scanning tunneling microscopy (STM) of DNA and RNA

1989 ◽  
Vol 47 ◽  
pp. 34-35
Author(s):  
Patricia G. Arscott ◽  
Gil Lee ◽  
Victor A. Bloomfield ◽  
D. Fennell Evans
Keyword(s):  
Molecular Structures ◽  
Inorganic Materials ◽  
Resolving Power ◽  
Scanning Tunneling ◽  
Tunneling Microscopy ◽  
Form And Function ◽  
Dna And Rna ◽  
Calf Thymus ◽  
And Function ◽  
The Relationship

STM is one of the most promising techniques available for visualizing the fine details of biomolecular structure. It has been used to map the surface topography of inorganic materials in atomic dimensions, and thus has the resolving power not only to determine the conformation of small molecules but to distinguish site-specific features within a molecule. That level of detail is of critical importance in understanding the relationship between form and function in biological systems. The size, shape, and accessibility of molecular structures can be determined much more accurately by STM than by electron microscopy since no staining, shadowing or labeling with heavy metals is required, and there is no exposure to damaging radiation by electrons. Crystallography and most other physical techniques do not give information about individual molecules.We have obtained striking images of DNA and RNA, using calf thymus DNA and two synthetic polynucleotides, poly(dG-me5dC)·poly(dG-me5dC) and poly(rA)·poly(rU).

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