Glycated Collagen Decreased Endothelial Cell Fibronectin Alignment in Response to Cyclic Stretch Via Interruption of Actin Alignment

2014 ◽  
Vol 136 (10) ◽  
Author(s):  
Dannielle S. Figueroa ◽  
Steven F. Kemeny ◽  
Alisa Morss Clyne
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Matrix Metalloproteinase ◽  
Cyclic Stretch ◽  
Matrix Metalloproteinase 2 ◽  
Mechanical Stimuli ◽  
Protein Alignment ◽  
Chronic Hyperglycemia ◽  
Native Collagen ◽  
In Cells

Hyperglycemia is a defining characteristic of diabetes, and uncontrolled blood glucose in diabetes is associated with accelerated cardiovascular disease. Chronic hyperglycemia glycates extracellular matrix (ECM) collagen, which can lead to endothelial cell dysfunction. In healthy conditions, endothelial cells respond to mechanical stimuli such as cyclic stretch (CS) by aligning their actin cytoskeleton. Other cell types, specifically fibroblasts, align their ECM in response to CS. We previously demonstrated that glycated collagen inhibits endothelial cell actin alignment in response to CS. The aim of this study was to determine the effect of glycated collagen on ECM remodeling and protein alignment in response to stretch. Porcine aortic endothelial cells (PAEC) seeded on native or glycated collagen coated elastic substrates were exposed to 10% CS. Cells on native collagen aligned subcellular fibronectin fibers in response to stretch, whereas cells on glycated collagen did not. The loss of fibronectin alignment was due to inhibited actin alignment in response to CS, since fibronectin alignment did not occur in cells on native collagen when actin alignment was inhibited with cytochalasin. Further, while ECM protein content did not change in cells on native or glycated collagen in response to CS, degradation activity decreased in cells on glycated collagen. Matrix metalloproteinase 2 (MMP-2) and membrane-associated type 1 matrix metalloproteinase (MT1-MMP) protein levels decreased, and therefore MMP-2 activity also decreased. These MMP changes may relate to c-Jun N-terminal kinase (Jnk) phosphorylation inhibition with CS, which has previously been linked to focal adhesion kinase (FAK). These data demonstrate the importance of endothelial cell actin tension in remodeling and aligning matrix proteins in response to mechanical stimuli, which is critical to vascular remodeling in health and disease.

The roles of adhesion molecules and proteinases in lymphocyte transendothelial migration

1996 ◽  
Vol 74 (6) ◽  
pp. 749-757 ◽  
Author(s):  
Joseph A. Madri ◽  
Donnasue Graesser ◽  
Tara Haas
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
T Cell ◽  
Matrix Metalloproteinase ◽  
Adhesion Molecules ◽  
Cell Monolayer ◽  
Transendothelial Migration ◽  
Matrix Metalloproteinase 2

T cell extravasation into perivascular tissue during inflammation involves transmigration through the endothelial cell (EC) layer and basement membrane. We have demonstrated that matrix metalloproteinase-2 (MMP-2) is induced in T cells upon adhesion to endothelial cells and that the induction of MMP-2 is mediated by binding of T cell VLA-4 to VCAM-1. Cloned murine Th1 cells antigenic to myelin basic protein, either expressing VLA-4 on their cell surface and causing experimental autoimmune encephalomyelitis (EAE) or not expressing VLA-4 and not causing EAE, were used. VLA-4 positive (+) T cells that adhered to VCAM-1 positive (+) endothelial cells exhibited an induction in MMP-2 mRNA, protein, and activity, whereas MMP-2 was not induced in the T cells that adhered to the VCAM-1 negative (−) endothelial cells or VLA-4 negative (−) T cells that adhered to VCAM-1+ endothelial cells. Incubating T cells with rVCAM-1-coated dishes showed that VLA-4+ T cells adhered to the molecule and that adhesion to rVCAM-1 was sufficient to induce MMP-2. VLA-4+ T cells that had transmigrated through a VCAM-1+ endothelial cell monolayer exhibited MMP-2 activity. TTMP-2 was shown to reduce T cell transmigration in vitro. Transmigrated T cells exhibited downregulation of VLA-4 and LFA-1 integrin surface expression and decreased binding to rVCAM-1 and rICAM-1 and increased binding to collagens I and IV, fibronectin, and laminin. Brain sections of mice demonstrated that as T cells migrated farther into the tissue, VLA-4 expression was lost, although CD4 expression remained unchanged. These results demonstrate that binding to VCAM-1 on endothelial cells induces MMP-2 in T cells, which, in turn, may facilitate T cell migration into perivascular tissue. The significance of these findings in the modulation of the inflammatory response is discussed.Key words: T lymphocyte, endothelial cell, matrix metalloproteinase, inflammation, transendothelial migration, integrins, cell adhesion molecules.

Caveolin-1 exists and may function in cardiomyocytes

2010 ◽  
Vol 88 (1) ◽  
pp. 73-76 ◽  
Author(s):  
Woo Jung Cho ◽  
Ava K. Chow ◽  
Richard Schulz ◽  
Edwin E. Daniel
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Matrix Metalloproteinase ◽  
Cardiac Myocytes ◽  
Ventricular Myocytes ◽  
Matrix Metalloproteinase 2 ◽  
Previous Evidence ◽  
Caveolin 1

Whether ventricular cardiac myocytes of mouse contain caveolin-1 is disputed. It has been claimed to be exclusively in nearby endothelial cell profiles. Recently, matrix metalloproteinase-2 (MMP-2) was reported to be present in mouse ventricular cardiac myocytes, colocalized with caveolin-1, and caveolin-1 knockout was found to cause the loss of MMP-2 from mouse ventricular cardiac myocytes and affect their functioning. To resolve this dispute, we labeled cardiac myocytes with caveolin-1 and endothelial cells with caveolin-2. Caveolin-2 is agreed to be present exclusively in endothelial cells. The results showed that mouse ventricular myocytes were labeled with caveolin-1 antibodies independently of any caveolin-2 labeling, and endothelial cells were labeled with both caveolin-1 and caveolin-2 antibodies. This confirms that caveolin-1 is present in mouse ventricular cardiac myocytes as well as endothelial cells. Previous evidence confirms that loss of caveolin-1 affects the function of mouse ventricular cardiac myocytes and suggests that MMP-2 may be involved.

scholarly journals Angiogenic microenvironment augments impaired endothelial responses under diabetic conditions

2014 ◽  
Vol 306 (8) ◽  
pp. C768-C778 ◽  
Author(s):  
Abdul Q. Sheikh ◽  
Courtney Kuesel ◽  
Toloo Taghian ◽  
Jennifer R. Hurley ◽  
Wei Huang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
High Glucose ◽  
Microvascular Complications ◽  
The Body ◽  
Type I ◽  
Chronic Hyperglycemia ◽  
Biomechanical Responses ◽  
Acute And Chronic Exposure

Diabetes-induced cardiomyopathy is characterized by cardiac remodeling, fibrosis, and endothelial dysfunction, with no treatment options currently available. Hyperglycemic memory by endothelial cells may play the key role in microvascular complications in diabetes, providing a potential target for therapeutic approaches. This study tested the hypothesis that a proangiogenic environment can augment diabetes-induced deficiencies in endothelial cell angiogenic and biomechanical responses. Endothelial responses were quantified for two models of diabetic conditions: 1) an in vitro acute and chronic hyperglycemia where normal cardiac endothelial cells were exposed to high-glucose media, and 2) an in vivo chronic diabetes model where the cells were isolated from rats with type I streptozotocin-induced diabetes. Capillary morphogenesis, VEGF and nitric oxide expression, cell morphology, orientation, proliferation, and apoptosis were determined for cells cultured on Matrigel or proangiogenic nanofiber hydrogel. The effects of biomechanical stimulation were assessed following cell exposure to uniaxial strain. The results demonstrate that diabetes alters cardiac endothelium angiogenic response, with differential effects of acute and chronic exposure to high-glucose conditions, consistent with the concept that endothelial cells may have a long-term “hyperglycemic memory” of the physiological environment in the body. Furthermore, endothelial cell exposure to strain significantly diminishes their angiogenic potential following strain application. Both diabetes and strain-associated deficiencies can be augmented in the proangiogenic nanofiber microenvironment. These findings may contribute to the development of novel approaches to reverse hyperglycemic memory of endothelium and enhance vascularization of the diabetic heart, where improved angiogenic and biomechanical responses can be the key factor to successful therapy.

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