Oxidation modifies the structure and function of the extracellular matrix generated by human coronary artery endothelial cells

2014 ◽  
Vol 459 (2) ◽  
pp. 313-322 ◽  
Author(s):  
Christine Y. Chuang ◽  
Georg Degendorfer ◽  
Astrid Hammer ◽  
John M. Whitelock ◽  
Ernst Malle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiovascular Disease ◽  
Extracellular Matrix ◽  
Arterial Wall ◽  
Structure And Function ◽  
Wall Structure ◽  
Peroxynitrous Acid ◽  
Human Coronary Artery ◽  
Cell Matrix ◽  
And Function

The extracellular matrix determines arterial wall structure and modulates the properties of associated cells. We show that the inflammation-associated oxidant peroxynitrous acid modifies human endothelial cell matrix, modulates gene expression and decreases cell adhesion, a key event in cardiovascular disease.

Morphological and Biochemical Features Affecting the Antithrombotic Properties of the Aorta in Adult Rabbits and Rabbit Pups

1998 ◽  
Vol 79 (05) ◽  
pp. 1034-1040 ◽  
Author(s):  
E. Nitschmann ◽  
L. Berry ◽  
S. Bridge ◽  
M. W. C. Hatton ◽  
M. Richardson ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Gel Electrophoresis ◽  
Arterial Wall ◽  
Structure And Function ◽  
Wall Structure ◽  
Matrix Structure ◽  
Antithrombotic Activity ◽  
Antithrombin Activity ◽  
And Function ◽  
Biochemical Features

SummaryWe hypothesised that there are important physiologic differences in arterial wall structure and function with respect to antithrombotic activity in the very young (pre-puberty) compared to adults. Electron microscopy, gel electrophoresis, and activity assays were used to examine differences in aorta structure and function comparing prepubertal rabbits (pups) to adult rabbits. Differences in endothelial function, extracellular matrix structure, proteoglycan (PG) distribution and glycosaminoglycan (GAG) content and function were shown. In both intima and media, total PG, chondroitin sulfate (CS) PG and heparan sulfate (HS) PG content were significantly increased in pups compared to adult rabbits. These findings corresponded to increased concentrations by mass analyses of CS GAG and DS GAG in aortas from pups. There was also a significant increase in antithrombin activity in pups due to HS GAG. In conclusion, differences in both structure and antithrombin activity of aortas from pups compared to adult rabbits suggest that young arteries may have greater antithrombotic potential that is, at least in part, related to increased HS GAG.

Effect of chronic ANG I-converting enzyme inhibition on aging processes. II. Large arteries

1994 ◽  
Vol 267 (1) ◽  
pp. R124-R135 ◽  
Author(s):  
J. B. Michel ◽  
D. Heudes ◽  
O. Michel ◽  
P. Poitevin ◽  
M. Philippe ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Arterial Wall ◽  
Left Ventricular ◽  
Structure And Function ◽  
Wall Structure ◽  
Large Artery ◽  
Converting Enzyme ◽  
Wall Stiffness ◽  
And Function

The consequences of hypertension and aging on cardiovascular structure and function are reputed to be similar, suggesting that blood pressure plays a role in the aging process. However, the exact relationship between aging, blood pressure, and the arterial structure-function relationship has not been demonstrated. To test the effects of aging, renin-angiotensin system, and pressure on the arterial wall, 20 normotensive male WAG/Rij rats were killed at 6, 12, 24, and 30 mo of age and compared with similar groups treated with an angiotensin (ANG)-converting enzyme inhibitor (ACEI), perindopril. Arterial function was determined by a systemic hemodynamic study and by in situ measurement of carotid compliance. Arterial wall structure was determined by histomorphometric and biochemical methods. Aging did not significantly modify blood pressure, but ACE inhibition decreased blood pressure significantly from 6 to 30 mo. Plasma renin activity decreased with age and increased with ACEI. Plasma atrial natriuretic factor increased with age and was significantly decreased with ACEI. Absolute and relative left ventricular weight increased with age, and ACEI delayed these increases. Arterial wall stiffness increased with age, as shown by a significant decrease in systemic and local arterial compliance and by an increase in aortic characteristic impedance. The increase in carotid wall compliance after poisoning of smooth muscle contractile function (KCN) was greater in young (6- and 12-mo old) than in old (24- and 30-mo old) rats. Chronic ACEI treatment increased basal carotid compliance values slightly and did not change KCN carotid compliance. The aortic and carotid luminal size increased regularly with age. Aging was associated without any change in absolute elastin content. In contrast, collagen content increased with aging. Aging was also associated with an increase in medial thickness. Medial thickening was mainly due to smooth muscle hypertrophy. Aging was associated with intimal proliferation, which became progressively thicker and collagen rich. ACEI treatment did not prevent aortic lumen enlargement but significantly postponed the increase in medial and intimal thickening. Biochemical determinations of the aortic wall components confirmed the morphometric data. In conclusion, the age-dependent large artery enlargement and stiffening were observed both in normotensive rats and in those rats whose blood pressure was lowered by ACEI. This suggests that aging and blood pressure affect arterial wall structure and function by different mechanisms.

scholarly journals Scavenger Receptors as Biomarkers and Therapeutic Targets in Cardiovascular Disease

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2453
Author(s):  
Gary A. Cuthbert ◽  
Faheem Shaik ◽  
Michael A. Harrison ◽  
Sreenivasan Ponnambalam ◽  
Shervanthi Homer-Vanniasinkam
Keyword(s):  
Cardiovascular Disease ◽  
Arterial Wall ◽  
Arterial Disease ◽  
Disease Diagnosis ◽  
Structure And Function ◽  
Scavenger Receptors ◽  
Lipid Particles ◽  
Membrane Bound ◽  
And Function ◽  
Progression Of Atherosclerosis

The process of atherosclerosis leads to the formation of plaques in the arterial wall, resulting in a decreased blood supply to tissues and organs and its sequelae: morbidity and mortality. A class of membrane-bound proteins termed scavenger receptors (SRs) are closely linked to the initiation and progression of atherosclerosis. Increasing interest in understanding SR structure and function has led to the idea that these proteins could provide new routes for cardiovascular disease diagnosis, management, and treatment. In this review, we consider the main classes of SRs that are implicated in arterial disease. We consider how our understanding of SR-mediated recognition of diverse ligands, including modified lipid particles, lipids, and carbohydrates, has enabled us to better target SR-linked functionality in disease. We also link clinical studies on vascular disease to our current understanding of SR biology and highlight potential areas that are relevant to cardiovascular disease management and therapy.

scholarly journals Molecular mechanisms of cardiomyocyte aging

2011 ◽  
Vol 121 (8) ◽  
pp. 315-329 ◽  
Author(s):  
Anna Sheydina ◽  
Daniel R. Riordon ◽  
Kenneth R. Boheler
Keyword(s):  
Gene Expression ◽  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Structure And Function ◽  
Functional Changes ◽  
Cellular Changes ◽  
Signalling Cascades ◽  
Time Changes ◽  
And Function

Western societies are rapidly aging, and cardiovascular diseases are the leading cause of death. In fact, age and cardiovascular diseases are positively correlated, and disease syndromes affecting the heart reach epidemic proportions in the very old. Genetic variations and molecular adaptations are the primary contributors to the onset of cardiovascular disease; however, molecular links between age and heart syndromes are complex and involve much more than the passage of time. Changes in CM (cardiomyocyte) structure and function occur with age and precede anatomical and functional changes in the heart. Concomitant with or preceding some of these cellular changes are alterations in gene expression often linked to signalling cascades that may lead to a loss of CMs or reduced function. An understanding of the intrinsic molecular mechanisms underlying these cascading events has been instrumental in forming our current understanding of how CMs adapt with age. In the present review, we describe the molecular mechanisms underlying CM aging and how these changes may contribute to the development of cardiovascular diseases.

Effects of Estrogen Treatment on Arterial Wall Structure and Function

Drugs ◽  
1994 ◽  
Vol 47 (Supplement 2) ◽  
pp. 42-51 ◽  
Author(s):  
Thomas B. Clarkson ◽  
Mary S. Anthony ◽  
Karen Potvin Klein
Keyword(s):  
Arterial Wall ◽  
Structure And Function ◽  
Estrogen Treatment ◽  
Wall Structure ◽  
And Function

scholarly journals Cardiac ECM: Its Epigenetic Regulation and Role in Heart Development and Repair

2020 ◽  
Vol 21 (22) ◽  
pp. 8610
Author(s):  
Rui Song ◽  
Lubo Zhang
Keyword(s):  
Cardiovascular Disease ◽  
Extracellular Matrix ◽  
Epigenetic Regulation ◽  
Heart Development ◽  
Structure And Function ◽  
Cellular Component ◽  
Tissue Architecture ◽  
Injury Type ◽  
Recent Developments ◽  
And Function

The extracellular matrix (ECM) is the non-cellular component in the cardiac microenvironment, and serves essential structural and regulatory roles in establishing and maintaining tissue architecture and cellular function. The patterns of molecular and biochemical ECM alterations in developing and adult hearts depend on the underlying injury type. In addition to exploring how the ECM regulates heart structure and function in heart development and repair, this review conducts an inclusive discussion of recent developments in the role, function, and epigenetic guidelines of the ECM. Moreover, it contributes to the development of new therapeutics for cardiovascular disease.

scholarly journals The α-dystrobrevins play a key role in maintaining the structure and function of the extracellular matrix–significance for protein elimination failure arteriopathies

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Matthew MacGregor Sharp ◽  
Jordan Cassidy ◽  
Thomas Thornton ◽  
James Lyles ◽  
Abby Keable ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Structure And Function ◽  
Basement Membranes ◽  
Amyloid Angiopathy ◽  
Post Mortem ◽  
Positive Correlation ◽  
And Function ◽  
The Brain ◽  
Astrocyte Endfeet

AbstractThe extracellular matrix (ECM) of the cerebral vasculature provides a pathway for the flow of interstitial fluid (ISF) and solutes out of the brain by intramural periarterial drainage (IPAD). Failure of IPAD leads to protein elimination failure arteriopathies such as cerebral amyloid angiopathy (CAA). The ECM consists of a complex network of glycoproteins and proteoglycans that form distinct basement membranes (BM) around different vascular cell types. Astrocyte endfeet that are localised against the walls of blood vessels are tethered to these BMs by dystrophin associated protein complex (DPC). Alpha-dystrobrevin (α-DB) is a key dystrophin associated protein within perivascular astrocyte endfeet; its deficiency leads to a reduction in other dystrophin associated proteins, loss of AQP4 and altered ECM. In human dementia cohorts there is a positive correlation between dystrobrevin gene expression and CAA. In the present study, we test the hypotheses that (a) the positive correlation between dystrobrevin gene expression and CAA is associated with elevated expression of α-DB at glial-vascular endfeet and (b) a deficiency in α-DB results in changes to the ECM and failure of IPAD. We used human post-mortem brain tissue with different severities of CAA and transgenic α-DB deficient mice. In human post-mortem tissue we observed a significant increase in vascular α-DB with CAA (CAA vrs. Old p < 0.005, CAA vrs. Young p < 0.005). In the mouse model of α-DB deficiency, there was early modifications to vascular ECM (collagen IV and BM thickening) that translated into reduced IPAD efficiency. Our findings highlight the important role of α-DB in maintaining structure and function of ECM, particularly as a pathway for the flow of ISF and solutes out of the brain by IPAD.

Enhanced Structure and Function of Stem Cell-Derived Beta-Like Cells Cultured on Extracellular Matrix

2020 ◽  
Author(s):  
Reena Singh ◽  
Richard Tan ◽  
Clara Tran ◽  
Thomas Loudovaris ◽  
Helen E. Thomas ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Stem Cell ◽  
Structure And Function ◽  
And Function ◽  
Cells Cultured

Vascular Fluid Mechanics, the Arterial Wall, and Atherosclerosis

1992 ◽  
Vol 114 (3) ◽  
pp. 274-282 ◽  
Author(s):  
R. M. Nerem
Keyword(s):  
Cell Culture ◽  
Blood Flow ◽  
Fluid Mechanics ◽  
Arterial Wall ◽  
Disease Process ◽  
The United States ◽  
Structure And Function ◽  
Medium Size ◽  
Important Relationship ◽  
And Function

Atherosclerosis, a disease of large- and medium-size arteries, is the chief cause of death in the United States and in most of the western world. Severe atherosclerosis interferes with blood flow; however, even in the early stages of the disease, i.e. during atherogenesis, there is believed to be an important relationship between the disease processes and the characteristics of the blood flow in the arteries. Atherogenesis involves complex cascades of interactions among many factors. Included in this are fluid mechanical factors which are believed to be a cause of the highly focal nature of the disease. From in vivo studies, there is evidence of hemodynamic influences on the endothelium, on intimal thickening, and on monocyte recruitment. In addition, cell culture studies have demonstrated the important effect of a cell’s mechanical environment on structure and function. Most of this evidence is for the endothelial cell, which is believed to be a key mediator of any hemodynamic effect, and it is now well documented that cultured endothelial monolayers, in response to a fluid flow-imposed laminar shear stress, undergo a variety of changes in structure and function. In spite of the progress in recent years, there are many areas in which further work will provide important new information. One of these is in the engineering of the cell culture environment so as to make it more physiologic. Animal studies also are essential in our efforts to understand atherogenesis, and it is clear that we need better information on the pattern of the disease and its temporal development in humans and animal models, as well as the specific underlying biologic events. Complementary to this will be in vitro model studies of arterial fluid mechanics. In addition, one can foresee an increasing role for computer modelling in our efforts to understand the pathophysiology of the atherogenic process. This includes not only computational fluid mechanics, but also modelling the pathobiologic processes taking place within the arterial wall. A key to the atherogenic process may reside in understanding how hemodynamics influences not only intimal smooth muscle cell proliferation, but also the recruitment of the monocyte/macrophage and the formation of foam cells. Finally, it will be necessary to begin to integrate our knowledge of cellular phenomena into a description of the biologic processes within the arterial wall and then to integrate this into a picture of the disease process itself.

Sign in / Sign up

Export Citation Format

Share Document