Extracellular Matrix Organization, Structure, and Function

Wiltz, Dena C.; Arevalos, Christopher; Balaoing, Liezl R.; Blancas, Alicia A.; Sapp, Matthew C.; Zhang, Xing; Grande‐Allen, K. Jane

doi:10.5772/52842

Cited by 22 publications

(24 citation statements)

References 119 publications

(174 reference statements)

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“…The glycosylated components lubricate the fibrosa and ventricularis layers during tissue deformation. Hyaluronan plays a major role in blunting the impact of constant valve movement, binding large amounts of water and forming a foam-like structure in the spongiosa that absorbs energy (109,132). The ventricularis, at the ventricular side of the valve, is made up of valvular endothelial cells, VICs, collagen, and radially oriented elastin fibers (22, 72,132).…”

Section: Aortic Valve Structure and Hemodynamicsmentioning

confidence: 99%

“…Hyaluronan plays a major role in blunting the impact of constant valve movement, binding large amounts of water and forming a foam-like structure in the spongiosa that absorbs energy (109,132). The ventricularis, at the ventricular side of the valve, is made up of valvular endothelial cells, VICs, collagen, and radially oriented elastin fibers (22, 72,132). The larger amount of matrix proteins, most especially elastin, within the ventricularis allows for fast and consistent compression during valve opening and closing (109).…”

Section: Aortic Valve Structure and Hemodynamicsmentioning

confidence: 99%

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Shear-Sensitive Genes in Aortic Valve Endothelium

Esmerats

Heath

2016

Antioxidants & Redox Signaling

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Significance: Currently, calcific aortic valve disease (CAVD) is only treatable through surgical intervention because the specific mechanisms leading to the disease remain unclear. In this review, we explore the forces and structure of the valve, as well as the mechanosensors and downstream signaling in the valve endothelium known to contribute to inflammation and valve dysfunction. Recent Advances: While the valvular structure enables adaptation to dynamic hemodynamic forces, these are impaired during CAVD, resulting in pathological systemic changes. Mechanosensing mechanisms-proteins, sugars, and membrane structures-at the surface of the valve endothelial cell relay mechanical signals to the nucleus. As a result, a large number of mechanosensitive genes are transcribed to alter cellular phenotype and, ultimately, induce inflammation and CAVD. Transforming growth factor-b signaling and Wnt/b-catenin have been widely studied in this context. Importantly, NADPH oxidase and reactive oxygen species/reactive nitrogen species signaling has increasingly been recognized to play a key role in the cellular response to mechanical stimuli. In addition, a number of valvular microRNAs are mechanosensitive and may regulate the progression of CAVD. Critical Issues: While numerous pathways have been described in the pathology of CAVD, no treatment options are available to avoid surgery for advanced stenosis and calcification of the aortic valve. More work must be focused on this issue to lead to successful therapies for the disease. Future Directions: Ultimately, a more complete understanding of the mechanisms within the aortic valve endothelium will lead us to future therapies important for treatment of CAVD without the risks involved with valve replacement or repair. Antioxid. Redox Signal. 25, 401-414.

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Section: Aortic Valve Structure and Hemodynamicsmentioning

confidence: 99%

Section: Aortic Valve Structure and Hemodynamicsmentioning

confidence: 99%

Shear-Sensitive Genes in Aortic Valve Endothelium

Esmerats

Heath

2016

Antioxidants & Redox Signaling

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“…102 PAVICs isolated from different layers of ECM have distinct levels of myofibroblast activation in response to environmental signals, 103 indicating that ECM composition and mechanical properties likely regulate the basal phenotype of these cells.…”

Section: The Extracellular Matrixmentioning

confidence: 99%

Section: The Extracellular Matrixmentioning

confidence: 99%

“…102 In a healthy valve, collagen forms fibrils by bundling procollagen triple peptide helices in the extracellular space, and this structure confers strength to the fibrosa in the direction of its alignment. 102 However, in CAVD, excessive collagen deposition and disrupted alignment can lead to increased matrix stiffness but reduced flexibility as the valve opens and closes (Figure 1). 7 Fibrillar collagen coated onto plastic plates can inhibited myofibroblast activation and calcific nodule formation of PAVICs compared with uncoated plates, 104,105 indicating that collagen might help inhibit pathogenic differentiation of VICs.…”

Section: The Extracellular Matrixmentioning

confidence: 99%

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Cardiac valve cells and their microenvironment—insights from in vitro studies

2014

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During every heartbeat, cardiac valves open and close coordinately to control unidirectional flow of blood. In this dynamically challenging environment, resident valve cells actively maintain homeostasis, but the signalling between cells and their microenvironment is complex. When this homeostasis is disrupted and valve opening obstructed, haemodynamic profiles can be altered and lead to impaired cardiac function. Currently, late stages of cardiac valve diseases are treated surgically, as there are no known drug therapies to reverse or halt disease progression. Consequently investigators have sought to understand the molecular and cellular mechanisms of valvular diseases usi in vitro cell culture systems and biomaterials scaffolds that can mimic extracellular microenvironment. In this Review we describe how signals in the extra cellular matrix regulate valve cell function. We propose that the cellular context is a critical factor when studying the molecular basis of valvular diseases in vitro, and one should consider how the surrounding matrix might influence cell signalling and functional outcomes in the valve. Investigators need to build a systems level understanding of the complex signalling network involved in valve regulation, to facilitate drug target identification and promote in situ or ex vivo heart valve regeneration.

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Polysaccharides and Glycoproteins

Kootala

Fernandes

2021

Biological Soft Matter

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Extracellular Matrix Organization, Structure, and Function

Cited by 22 publications

References 119 publications

Shear-Sensitive Genes in Aortic Valve Endothelium

Shear-Sensitive Genes in Aortic Valve Endothelium

Cardiac valve cells and their microenvironment—insights from in vitro studies

Polysaccharides and Glycoproteins

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