Posts Tagged: extracellular matrix

The Vasculature in Prediabetes

The Vasculature in Prediabetes

David H. Wasserman, Thomas J. Wang, Nancy J. Brown

Insulin access is determined by (1) vascular reactivity; (2) microcirculatory hemodynamics; and (3) capillary insulin permeability (determined by vesicular or paracellular fluid phase transport). Vascular reactivity and microcirculatory hemodynamics are determined by endocrine factors, paracrine factors, cytokines, and microcirculatory architecture. Capillary insulin efflux is determined by the balance between hydrostatic and oncotic pressures. [Powerpoint File]

Cardiac Fibrosis: The Fibroblast Awakens

Cardiac Fibrosis: The Fibroblast Awakens

Joshua G. Travers, Fadia A. Kamal, Jeffrey Robbins, Katherine E. Yutzey, Burns C. Blaxall

Selection of signaling pathways regulating myofibroblast activation and potential therapeutic targets for cardiac fibrosis. Numerous signaling pathways have been implicated in the activation of cardiac fibroblasts and the induction of pathological remodeling; targeting these signals is of intense scientific interest toward development of novel therapeutic strategies. Cardiac injury promotes the activation of receptors such as the β-adrenergic receptor (β-AR), activin receptor-like kinase 5 (ALK5), type 1 angiotensin II receptor (AT1R), endothelin receptor (ETR), transient receptor potential channel C6 (TRPC6), and integrins, which induces pathological signaling through numerous mediators, leading to the transcription of factors that regulate myofibroblast activation and fibrotic remodeling. Proposed antifibrotic therapeutic targets are marked with a red X. AC indicates adenylate cyclase; ERK1/2, extracellular regulated kinase 1/2; GRK2, G-protein–coupled receptor kinase 2; JNK, c-JUN N-terminal kinase; MEK1, mitogen-activated protein kinase kinase 1; MRTF, myocardin-related transcription factor; NFAT, nuclear factor of activated T cells; PI3K, phosphoinositide 3-kinase; TAK1, TGF-β–activated kinase 1; and TGF-β, transforming growth factor β. [Powerpoint File]

Cardiac Fibrosis: The Fibroblast Awakens

Cardiac Fibrosis: The Fibroblast Awakens

Joshua G. Travers, Fadia A. Kamal, Jeffrey Robbins, Katherine E. Yutzey, Burns C. Blaxall

Characteristics and functions of activated cardiac myofibroblasts. Cardiac fibroblasts respond to pathological stress and environmental stimuli by transforming into myofibroblasts that (1) express elevated levels of various proinflammatory and profibrotic factors that directly contribute to inflammatory cell infiltration and fibroblast proliferation, (2) secrete high levels of matrix metalloproteinases and other extracellular matrix (ECM) degrading enzymes that facilitate fibroblast migration, and (3) contribute to the deposition of collagen and other ECM proteins, leading to scar formation. Although this adaptive fibrotic scar tissue maintains the structural integrity and pressure-generating capacity of the heart, myofibroblast persistence eventually leads to the development of adverse changes in ventricular structure and compliance, leading to the progression to heart failure. [Powerpoint File]

Cardiac Fibrosis: The Fibroblast Awakens

Cardiac Fibrosis: The Fibroblast Awakens

Joshua G. Travers, Fadia A. Kamal, Jeffrey Robbins, Katherine E. Yutzey, Burns C. Blaxall

Proposed sources of cardiac myofibroblasts. The source(s) of activated cardiac fibroblasts that accumulate in response to various pathological insults remains under active investigation. Mounting evidence suggests that activated myofibroblasts in the fibrotic heart derive from the proliferation and activation of resident fibroblasts, as these cells are remarkably sensitive to pathological insult and represent a feasible source of matrix-producing cells during cardiac fibrosis. Numerous additional precursors to the fibroblast population in the injured heart have been proposed; these include endothelial and epicardial cells, through epithelial–mesenchymal transition and endothelial–mesenchymal transition, respectively, hematopoietic bone marrow–derived cells, perivascular cells, and fibrocytes. Although supporting evidence exists for cellular sources of activated fibroblasts denoted by question marks, controversy remains about the functional contribution of these cell types to the cardiac myofibroblast population. Biomarkers with greater specificity will be required to fully characterize the pathophysiological relevance of these cell types in the cardiac fibrotic response, which will enable potential targeting for antifibrotic therapies. [Powerpoint File]

Vascular Smooth Muscle Cells in Atherosclerosis

Vascular Smooth Muscle Cells in Atherosclerosis

Martin R. Bennett, Sanjay Sinha, Gary K. Owens

Schematic summarization of the current knowledge of the identity and origins of vascular smooth muscle cells (VSMCs), macrophages, and putative derivatives of these cells within advanced atherosclerotic lesions. The solid lines illustrate known pathways that give rise to lesion cells, whereas dotted lines with a “?” indicate putative pathways not yet directly validated in animal models or humans. Klf4 indicates Kruppel-like factor 4 (Illustration Credit: Ben Smith). [Powerpoint File]

Vascular Smooth Muscle Cells in Atherosclerosis

Vascular Smooth Muscle Cells in Atherosclerosis

Martin R. Bennett, Sanjay Sinha, Gary K. Owens

Schematic illustration of several processes that vascular smooth muscle cells (VSMCs) undergo in advanced atherosclerotic plaques. IL indicates interleukin; MCP, monocyte chemoattractant protein, PDGF, platelet-derived growth factor; and TNF, tumor necrosis factor (Illustration Credit: Ben Smith). [Powerpoint File]

Matrix as an Interstitial Transport System

Matrix as an Interstitial Transport System

Dong Fan, Esther E. Creemers, Zamaneh Kassiri

Multiple functions of heparan sulfate proteoglycans. Heparan sulfate chains serve as a coreceptor for growth factors on the same cell, or on an adjacent cell, and also serve as a reservoir for growth factors in the extracellular matrix. [Powerpoint File]

Matrix as an Interstitial Transport System

Matrix as an Interstitial Transport System

Dong Fan, Esther E. Creemers, Zamaneh Kassiri

Connectivity between cardiomyocyte and cardiac fibroblasts. A, Cultured neonatal rat ventricular myocytes and fibroblasts labeled for microtubules (α-tubulin) and F-actin (rhodamine-conjugated phalloidin). Arrows point to tunneling nanotubes (TNTs). B, Thin structures similar to TNTs in adult mouse heart tissue (arrow). Scale, 10 μm. A and B, Adapted from He et al174 with permission of the publisher. Copyright © 2011, Oxford University Press. C, Proposed structure for TNTs between a cardiomyocyte and a cardiofibroblast comprising F-actin and microtubules. Mitochondrial transport along F-action is mediated by myosin V and along microtubule by kinesin molecules. Cytoplasmic vesicles and other materials (eg, lysosomes and endosomes) can also be transported through the nanotube. Authorization for this adaptation has been obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation. CM indicates cardiomyocyte; FB, fibroblast; and WGA, wheat germ agglutinin. [Powerpoint File]

Dynamic Changes in Myocardial Matrix and Relevance to Disease: Translational Perspectives

Dynamic Changes in Myocardial Matrix and Relevance to Disease: Translational Perspectives

Ai-Hsien Li, Peter P. Liu, Francisco J. Villarreal, Ricardo A. Garcia

Normal 3-dimensional representation of cardiac microstructure. A representative transmural block taken from the ventricular wall (A) shows myofiber orientation which varies transmurally. Myocyte bundles are organized in sheets (B). Fibrillar collagens are seen interconnecting individual myocytes as well as adjacent sheets. Adapted from Legrice et al133 with permission of the publisher. Copyright © 2005, Springer. Authorization for this adaptation has been obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation. LV indicates left ventricle. [Powerpoint File]

Cell–Matrix Interactions in the Pathobiology of Calcific Aortic Valve Disease: Critical Roles for Matricellular, Matricrine, and Matrix Mechanics Cues

Cell–Matrix Interactions in the Pathobiology of Calcific Aortic Valve Disease: Critical Roles for Matricellular, Matricrine, and Matrix Mechanics Cues

Jan-Hung Chen, Craig A. Simmons

Mechanisms by which the valve ECM may regulate cell function to contribute to the pathobiology of calcific aortic valve disease. Illustration credit: Cosmocyte/Ben Smith. [Powerpoint File]