Characterization of type I collagen gels modified by glycation

Francis-Sedlak, Megan; Uriel, Shiri; Larson, Jeffery C.; Greisler, Howard P.; Venerus, David C.; Brey, Eric M.

doi:10.1016/j.biomaterials.2008.12.014

Cited by 94 publications

(98 citation statements)

References 34 publications

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“…Others have demonstrated transient, decreased sprouting responses in matrices glycated with glucose-6-phospate but also noted increased branching and tortuosity (34,35). Of note, direct exposure to high concentrations of glucose is known to affect cells adversely (36), whereas AGEs can have direct antiangiogenic effects on ECs (37,38).…”

Section: Discussionmentioning

confidence: 99%

Matrix stiffening promotes a tumor vasculature phenotype

Bordeleau

Mason

Lollis

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

324

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Tumor microvasculature tends to be malformed, more permeable, and more tortuous than vessels in healthy tissue, effects that have been largely attributed to up-regulated VEGF expression. However, tumor tissue tends to stiffen during solid tumor progression, and tissue stiffness is known to alter cell behaviors including proliferation, migration, and cell-cell adhesion, which are all requisite for angiogenesis. Using in vitro, in vivo, and ex ovo models, we investigated the effects of matrix stiffness on vessel growth and integrity during angiogenesis. Our data indicate that angiogenic outgrowth, invasion, and neovessel branching increase with matrix cross-linking. These effects are caused by increased matrix stiffness independent of matrix density, because increased matrix density results in decreased angiogenesis. Notably, matrix stiffness up-regulates matrix metalloproteinase (MMP) activity, and inhibiting MMPs significantly reduces angiogenic outgrowth in stiffer crosslinked gels. To investigate the functional significance of altered endothelial cell behavior in response to matrix stiffness, we measured endothelial cell barrier function on substrates mimicking the stiffness of healthy and tumor tissue. Our data indicate that barrier function is impaired and the localization of vascular endothelial cadherin is altered as function of matrix stiffness. These results demonstrate that matrix stiffness, separately from matrix density, can alter vascular growth and integrity, mimicking the changes that exist in tumor vasculature. These data suggest that therapeutically targeting tumor stiffness or the endothelial cell response to tumor stiffening may help restore vessel structure, minimize metastasis, and aid in drug delivery.tumor stiffness | endothelial cells | vascular permeability | glycation | extracellular matrix T he ingrowth of newly sprouted blood vessels is necessary for solid tumor growth, and tumor vasculature is typically malformed, leakier, and more tortuous than the vasculature of normal tissues (1-3). Generally, aberrant tumor vasculature is considered to be caused by up-regulated VEGF expression resulting in chaotic vascular growth and failure to establish mature, well-regulated networks (4, 5). Here, we propose a different hypothesis, namely that extracellular matrix (ECM) mechanical properties also contribute to the aberrant vascular phenotype seen in tumors.Solid tumor tissue is typically stiffer than native, healthy tissue (1, 6). Increased ECM stiffness within tumors is caused primarily by both increased collagen deposition and increased cross-linking within the tumor stroma (7). Increased ECM density and crosslinking are associated with poor prognosis in a number of cancers (8, 9). Many studies have investigated the role of matrix density on angiogenesis and, in both collagen and fibrin matrices, have shown that angiogenesis decreases with increasing matrix concentration (10-13). Increased matrix density appears to act as a physical barrier that restricts cell migration, and cells rely on matr...

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Section: Discussionmentioning

confidence: 99%

Matrix stiffening promotes a tumor vasculature phenotype

Bordeleau

Mason

Lollis

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

324

View full text Add to dashboard Cite

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“…Using this method, an increase in AGE products has been associated with an increase in rat aorta stiffness with age (Bruel and Oxlund 1996). These changes to the ECM caused by collagen cross-linking can further influence cellular behavior, leading to additional biological and mechanical changes (Francis-Sedlak et al 2009). As noted earlier, the enzyme lysyl oxidase is involved in elastin cross-linking.…”

Section: Glycation Of Arteriesmentioning

confidence: 97%

“…The process of AGE formation is an irreversible chemical reaction that results in the cross-linking of collagen molecules through the Maillard reaction (Francis-Sedlak et al 2009). Advanced glycation end products in collagen have been shown to affect mechanical properties of tissue, including arteries and articular cartilage (Aronson 2003;Chen et al 2002;Verzijl et al 2002;Wagner et al 2006;Stephen et al 2013b).…”

Section: Glycation Of Arteriesmentioning

confidence: 99%

Biomechanical Behavior of Atherosclerotic Plaque

Topoleski

Stephen

2014

PanVascular Medicine

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Atherosclerosis is a disease in which deposits, called atherosclerotic plaques, build up in the arterial wall. Their presence can become critical when the plaques restrict blood flow and cause a stroke or a heart attack. Standard interventions to treat plaques and restore blood flow through an artery require the application of mechanical force to keep the plaque from obstructing the lumen. Because the cardiovascular system, and specifically blood vessels, has an essential mechanical function in maintaining health, understanding changes in mechanical behaviors in blood vessels caused by disease is critical. Therefore, studying blood vessel and plaque mechanical behaviors, and treating the tissues as materials, may provide essential information on predicting, treating, or preventing cardiovascular diseases. In this chapter, we discuss the current state of understanding of the mechanical behavior of atherosclerotic plaques. The mechanical behavior of a plaque will depend on its constituent materials and its geometry. We begin by discussing the nature of material properties, followed by a review of general arterial mechanics. Then we describe and discuss the studies that have investigated the mechanical responses of atherosclerotic plaques under different loading conditions. In summary, it is clear that our comprehension of the mechanical behavior of atherosclerotic plaque has made enormous advances in recent years. Unfortunately, there are still large gaps in our understanding of many aspects of cardiovascular disease: we still require better knowledge of plaque material properties and behaviors.

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“…21,22 Research has demonstrated that diabetes can exacerbate connective tissue remodeling and amplify these biomechanical changes. 23 More importantly, the Barbados Eye Study had found that diabetes was a risk factor for increased IOP in followup. 24 The Baltimore eye survey found little or no association between glaucoma and either insulin dependent or noninsulin dependent diabetes.…”

Section: Discussionmentioning

confidence: 99%

A study of relation between primary open angle glaucoma and type II diabetes mellitus

et al. 2018

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Background: Primary open angle glaucoma has been characterized by its adult onset, IOP >21mmHg at some point in the course of the disease, open angles on gonioscopy, glaucomatous visual field changes and glaucomatous optic nerve damage. POAG is a multi-factorial disease such as age, black race, positive family history, high myopia etc. Diabetes mellitus has also been considered as one of the risk factors, but no major study has been conducted to provide tangible proof.Methods: This cross sectional, case control study was conducted to determine whether diabetes stands as a risk factor in development of glaucoma. The selected patients were divided into 3 groups based on inclusion and exclusion criteria. They were subjected to complete ocular examination including gonioscopy and perimetry.Results: The 16 patients from 50 of the diabetic group (28%) were found to have POAG. The p value was <0.005 which was statistically significant. Also, no correlation was found between blood sugar and IOP levels in these patients.Conclusions: These data show a significant correlation between diabetes and glaucoma. Further studies are warranted to determine its actual role in pathogenesis of glaucoma.

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Characterization of type I collagen gels modified by glycation

Cited by 94 publications

References 34 publications

Matrix stiffening promotes a tumor vasculature phenotype

Matrix stiffening promotes a tumor vasculature phenotype

Biomechanical Behavior of Atherosclerotic Plaque

A study of relation between primary open angle glaucoma and type II diabetes mellitus

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