scholarly journals The role of basement membranes in cardiac biology and disease

2021 ◽  
Author(s):  
Erin Boland ◽  
Fabio Quondamatteo ◽  
Tom Van Agtmael
Keyword(s):  
Basement Membrane ◽  
Cardiac Development ◽  
Basement Membranes ◽  
Cell Behaviour ◽  
Structural Support ◽  
Supportive Environment ◽  
Functional Consequences ◽  
Membrane Defects ◽  
Cardiovascular Pathologies

Basement membranes are highly specialised extracellular matrix structures that within the heart underlie endothelial cells and surround cardiomyocytes and vascular smooth muscle cells. They generate a dynamic and structurally supportive environment throughout cardiac development and maturation by providing physical anchorage to the underlying interstitium, structural support to the tissue, and by influencing cell behaviour and signalling. While this provides a strong link between basement membrane dysfunction and cardiac disease, the role of the basement membrane in cardiac biology remains under-researched and our understanding regarding the mechanistic interplay between basement membrane defects and their morphological and functional consequences remain important knowledge-gaps. In this review we bring together emerging understanding of basement membrane defects within the heart including in common cardiovascular pathologies such as contractile dysfunction and highlight some key questions that are now ready to be addressed.

scholarly journals The Non-Fibrillar Side of Fibrosis: Contribution of the Basement Membrane, Proteoglycans, and Glycoproteins to Myocardial Fibrosis

2019 ◽  
Vol 6 (4) ◽  
pp. 35 ◽  
Author(s):  
Michael Chute ◽  
Preetinder Aujla ◽  
Sayantan Jana ◽  
Zamaneh Kassiri
Keyword(s):  
Basement Membrane ◽  
Myocardial Fibrosis ◽  
Direct Evidence ◽  
Fibrillar Collagen ◽  
Collagen Types ◽  
Structural Support ◽  
Ecm Proteins ◽  
Fibrillar Collagens ◽  
Extracellular Molecules

The extracellular matrix (ECM) provides structural support and a microenvironmentfor soluble extracellular molecules. ECM is comprised of numerous proteins which can be broadly classified as fibrillar (collagen types I and III) and non-fibrillar (basement membrane, proteoglycans, and glycoproteins). The basement membrane provides an interface between the cardiomyocytes and the fibrillar ECM, while proteoglycans sequester soluble growth factors and cytokines. Myocardial fibrosis was originally only linked to accumulation of fibrillar collagens, but is now recognized as the expansion of the ECM including the non-fibrillar ECM proteins. Myocardial fibrosis can be reparative to replace the lost myocardium (e.g., ischemic injury or myocardial infarction), or can be reactive resulting from pathological activity of fibroblasts (e.g., dilated or hypertrophic cardiomyopathy). Contribution of fibrillar collagens to fibrosis is well studied, but the role of the non-fibrillar ECM proteins has remained less explored. In this article, we provide an overview of the contribution of the non-fibrillar components of the extracellular space of the heart to highlight the potential significance of these molecules in fibrosis, with direct evidence for some, although not all of these molecules in their direct contribution to fibrosis.

scholarly journals Regulation of the differentiation and behaviour of extra-embryonic endodermal cells by basement membranes

2001 ◽  
Vol 114 (5) ◽  
pp. 931-939 ◽  
Author(s):  
P. Murray ◽  
D. Edgar
Keyword(s):  
Stem Cells ◽  
Basement Membrane ◽  
Embryonic Stem ◽  
Basement Membranes ◽  
Embryoid Bodies ◽  
Endodermal Differentiation ◽  
And Migration ◽  
The Individual ◽  
Endodermal Cells

Both the extracellular matrix and parathyroid hormone-related peptide (PTHrP) have been implicated in the differentiation and migration of extra-embryonic endodermal cells in the pre-implantation mammalian blastocyst. In order to define the individual roles and interactions between these factors in endodermal differentiation, we have used embryoid bodies derived from Lamc1(-/-) embryonic stem cells that lack basement membranes. The results show that in the absence of basement membranes, increased numbers of both visceral and parietal endodermal cells differentiate, but they fail to form organised epithelia. Furthermore, although parietal endodermal cells only migrate away from control embryoid bodies in the presence of PTHrP, they readily migrate from Lamc1(-/-) embryoid bodies in the absence of PTHrP, and this migration is unaffected by PTHrP. Thus, the basement membrane between epiblast and extra-embryonic endoderm is required for the proper organisation of visceral and parietal endodermal cells and also restricts their differentiation to maintain the population of primitive endodermal stem cells. Moreover, this basement membrane inhibits migration of parietal endodermal cells, the role of PTHrP being to stimulate delamination of parietal endodermal cells from the basement membrane rather than promoting migration per se.

The Role of Collagen, Fibronectin, Chondronectin and Laminin in Cell Adhesion

1982 ◽  
Vol 40 ◽  
pp. 102-105
Author(s):  
Hynda K. Kleinman ◽  
George R. Martin
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Blood Cells ◽  
Basement Membranes ◽  
Extracellular Matrices ◽  
Structural Support ◽  
Tissue Organization ◽  
Attachment Proteins ◽  
Surrounding Extracellular Matrix

Most cells other than blood cells interact with extracellular matrices composed of various types of collagens, proteoglycans and a newly described group of glycoproteins termed the attachment proteins. Variations in the composition of the extracellular matrix determine the uniqueness of tissues, such as cartilage, bone, dermis and basement membranes. These matrices have numerous functions, including providing structural support to rigid tissues (cartilage, tooth and bone), regulating the passage of macromolecules (kidney basement membrane), and allowing tissues to stretch (blood vessels and skin). In addition, these matrices have potent influences upon the cells which populate them. The anchorage, growth, differentiation, and motility of the resident cells are all determined by their surrounding extracellular matrix. Such matrices are critically important in embryonic development, tissue organization and wound healing.

Transendothelial migration of lymphocytes across high endothelial venules into lymph nodes is affected by metalloproteinases

Blood ◽  
2001 ◽  
Vol 98 (3) ◽  
pp. 688-695 ◽  
Author(s):  
Christelle Faveeuw ◽  
Graham Preece ◽  
Ann Ager
Keyword(s):  
Basement Membrane ◽  
Lymph Nodes ◽  
Transendothelial Migration ◽  
Basement Membranes ◽  
Lymphocyte Migration ◽  
Endothelial Lining ◽  
High Endothelial Venules ◽  
Mmp Inhibitor ◽  
Cell Lining

Abstract The migration of lymphocytes from the bloodstream into lymph nodes (LNs) via high endothelial venules (HEVs) is a prerequisite for the detection of processed antigen on mature dendritic cells and the initiation of immune responses. The capture and arrest of lymphocytes from flowing blood is mediated by the multistep adhesion cascade, but the mechanisms that lymphocytes use to penetrate the endothelial lining and the basement membrane of HEVs are poorly understood. Matrix metalloproteinases (MMPs) control the metastatic spread of tumor cells by regulating the penetration blood vessel basement membranes. In this study, synthetic and natural inhibitors were used to determine the role of MMPs and MMP-related enzymes in regulating lymphocyte extravasation in mice. Mice were treated systemically with the hydroxamate-based MMP inhibitor Ro 31-9790 and plasma monitored for effective levels of Ro 31-9790, which block shedding of L-selectin. The total numbers of lymphocytes recruited into LNs were not altered, but L-selectin levels were higher in mice treated with Ro 31-9790. A reduced number of lymphocytes completed diapedesis and there was an increase in the number of lymphocytes in the endothelial cell lining, rather than the lumen or the basement membrane of HEVs. Lymphocyte migration and L-selectin expression in the spleen were not altered by Ro 31-9790 treatment. Two MMP inhibitors, TIMP1 and Ro 32-1541, did not block L-selectin shedding and had no effect on lymphocyte migration across HEVs. These results suggest that metalloproteinase activity is required for lymphocyte transmigration across HEVs into LNs and provide evidence for the concept that metalloproteinases are important players in some forms of transendothelial migration.

scholarly journals The Absence of Nidogen 1 Does Not Affect Murine Basement Membrane Formation

2000 ◽  
Vol 20 (18) ◽  
pp. 7007-7012 ◽  
Author(s):  
Monzur Murshed ◽  
Neil Smyth ◽  
Nicolai Miosge ◽  
Jörg Karolat ◽  
Thomas Krieg ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Embryonic Stem ◽  
Collagen Iv ◽  
Basement Membranes ◽  
Null Mutation ◽  
Membrane Structures ◽  
Membrane Formation ◽  
Nidogen 1

ABSTRACT Nidogen 1 is a highly conserved protein in mammals,Drosophila melanogaster, Caenorhabditis elegans, and ascidians and is found in all basement membranes. It has been proposed that nidogen 1 connects the laminin and collagen IV networks, so stabilizing the basement membrane, and integrates other proteins, including perlecan, into the basement membrane. To define the role of nidogen 1 in basement membranes in vivo, we produced a null mutation of the NID-1 gene in embryonic stem cells and used these to derive mouse lines. Homozygous animals produce neither nidogen 1 mRNA nor protein. Surprisingly, they show no overt abnormalities and are fertile, their basement membrane structures appearing normal. Nidogen 2 staining is increased in certain basement membranes, where it is normally only found in scant amounts. This occurs by either redistribution from other extracellular matrices or unmasking of nidogen 2 epitopes, as its production does not appear to be upregulated. The results show that nidogen 1 is not required for basement membrane formation or maintenance.

Importance of nidogen binding to laminin gamma1 for branching epithelial morphogenesis of the submandibular gland

Development ◽  
1997 ◽  
Vol 124 (3) ◽  
pp. 683-691 ◽  
Author(s):  
Y. Kadoya ◽  
K. Salmivirta ◽  
J.F. Talts ◽  
K. Kadoya ◽  
U. Mayer ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Submandibular Gland ◽  
Driving Forces ◽  
Basement Membranes ◽  
Epithelial Morphogenesis ◽  
Epidermal Growth ◽  
Membrane Components ◽  
Blocking Antibodies

Epithelial-mesenchymal interactions are major driving forces for the development of most solid organs. The importance of these interactions was first shown for the embryonic submandibular gland more than 40 years ago. We here present evidence that interactions between two basement membrane components, nidogen (entactin) and laminin gamma1 chain, could be important for epithelial-mesenchymal interactions in this gland. Nidogen mRNA was detected by in situ hybridization in the mesenchyme, and yet the protein was detected in epithelial and endothelial basement membranes. The role of nidogen-laminin interactions for epithelial morphogenesis was studied by applying antibodies to submandibular gland organ cultures. Antibodies reacting strongly with the nidogen-binding site of laminin gamma1 chain drastically perturbed branching epithelial morphogenesis. Electron microscopy of the epithelial-mesenchymal interface showed that blocking antibodies disrupted the formation of the basement membrane. Epidermal growth factor was shown to increase the expression of nidogen in mesenchyme, and could counteract the effect of the blocking antibodies. We suggest that nidogen could be an important mesenchymal factor for submandibular gland development.

Enhanced assembly of basement membrane matrix by endodermal cells in response to fibronectin substrata

1991 ◽  
Vol 99 (2) ◽  
pp. 443-451
Author(s):  
M.R. Austria ◽  
J.R. Couchman
Keyword(s):  
Extracellular Matrix ◽  
Basement Membrane ◽  
Basement Membranes ◽  
Binding Domain ◽  
Type I ◽  
Matrix Assembly ◽  
Matrix Deposition ◽  
Membrane Matrix ◽  
The Matrix

Basement membranes are complex extracellular matrices contributing to the regulation of growth, migration and differentiation of many cell types. However, little is known about the mechanisms regulating the deposition and assembly of basement membrane from its constituents. We have investigated the role of extracellular matrix molecules in the control of basement membrane matrix assembly by cultured endodermal (PFHR-9) cells. In the presence of fibronectin-depleted serum, substrata of fibronectin or laminin induced an increase in deposition of laminin, type IV collagen and proteoglycans by PFHR-9 cells, in comparison to cells adherent to type I collagen-coated, vitronectin-coated or uncoated substrata. Direct effects of fibronectin or laminin on the degree of cell spreading or rate of proliferation were not responsible for enhanced matrix deposition. The effect did not result from a redirection of basement membrane components to the matrix, since there was no decrease in matrix constituents released to the culture supernatants. Furthermore, the synthesis and release of other molecules that are not basement membrane constituents was unaltered in response to different extracellular matrix substrata. Experiments with fibronectin fragments showed that a 105 × 10(3) Mr ‘cell’-binding domain (containing the cell attachment sequence Arg-Gly-Asp-Ser) was an important contributor to enhanced matrix deposition, while the N-terminal 29 × 10(3) Mr heparin-binding domain also contributed to the effect, particularly with respect to heparan sulfate proteoglycan deposition. It seems that fibronectin has a dual role of action in promoting basement membrane matrix assembly, through direct cell surface interactions, and through the binding of fibronectin to other matrix components that may nucleate or stabilize the matrix assembly.

The role of endothelin-1 in myocarditis and inflammatory cardiomyopathy: old lessons and new insights

2005 ◽  
Vol 83 (1) ◽  
pp. 47-62 ◽  
Author(s):  
Li L Yang ◽  
Sara Arab ◽  
Peter Liu ◽  
Duncan J Stewart ◽  
Mansoor Husain
Keyword(s):  
Expression Profiling ◽  
Cardiac Development ◽  
Molecular Genetic ◽  
Published Data ◽  
Inflammatory Cardiomyopathy ◽  
Endothelin 1 ◽  
Micro Array ◽  
Functional Consequences ◽  
Genetic Mouse Models

Endothelin-1 has emerged as an important participant in the pathophysiology of a variety of cardiovascular diseases, where it may act on endocrine, paracrine and autocrine bases. Here we review its regulated biosynthesis, receptor-mediated signaling, and functional consequences in the heart, with particular emphasis on cardiac development and disease. Exploring published data employing molecular genetic mouse models of endothelin dysregulation, we highlight its heretofore underappreciated role as a pro-inflammatory cytokine. We also present novel micro-array data from one such mouse model, which implicate the specific downstream pathways that may mediate endothelin-1's effects.Key words: endothelin-1, cardiac development, inflammation, transgenic mice, gene expression profiling.

Physical Properties of Isolated Perfused Renal Tubular Basement Membranes

1971 ◽  
Vol 29 ◽  
pp. 390-391
Author(s):  
Jared Grantham ◽  
Larry Welling
Keyword(s):  
Basement Membrane ◽  
Basement Membranes ◽  
Transport Mechanisms ◽  
Permeability Characteristics ◽  
Peritubular Capillaries ◽  
Strategic Location ◽  
Tubular Lumen ◽  
Glomerular Filtrate ◽  
Urine Formation ◽  
Renal Tubular

In the course of urine formation in mammalian kidneys over 90% of the glomerular filtrate moves from the tubular lumen into the peritubular capillaries by both active and passive transport mechanisms. In all of the morphologically distinct segments of the renal tubule, e.g. proximal tubule, loop of Henle and distal nephron, the tubular absorbate passes through a basement membrane which rests against the basilar surface of the epithelial cells. The basement membrane is in a strategic location to affect the geometry of the tubules and to influence the movement of tubular absorbate into the renal interstitium. In the present studies we have determined directly some of the mechanical and permeability characteristics of tubular basement membranes.

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