On the biomechanical role of glycosaminoglycans in the aortic heart valve leaflet

Eckert, Chad E.; Fan, Rong; Mikulis, Brandon; Barron, Mathew; Carruthers, Christopher A.; Friebe, Vincent M.; Vyavahare, Naren; Sacks, Michael S.

doi:10.1016/j.actbio.2012.09.031

Cited by 63 publications

(59 citation statements)

References 49 publications

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“…While there were minimal differences between genotypes at each age (supporting previous studies negating the role of PGs and GAGs in tendon mechanics), there were changes with the effect of aging on those properties and changes in the realignment of collagen fibers. Recent studies suggest that GAGs and PGs may play a bigger role in fiber-fiber and fiber-matrix interactions at low strain levels, which is supported in this study, where changes in fiber re-alignment were found at small strain changes, such as preconditioning and in the toe region [28]. Overall, this data suggests that mechanical property measurements alone do not fully account for the functional changes that occur with structural alterations, especially when concerning alterations at much lower hierarchical levels.…”

Section: Days 300 Days 570 Dayssupporting

confidence: 87%

Effect of Age and Proteoglycan Deficiency on Collagen Fiber Re-Alignment and Mechanical Properties in Mouse Supraspinatus Tendon

Connizzo¹,

Sarver

Iozzo

et al. 2013

Journal of Biomechanical Engineering

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Collagen fiber realignment is one mechanism by which tendon responds to load. Re-alignment is altered when the structure of tendon is altered, such as in the natural process of aging or with alterations of matrix proteins, such as proteoglycan expression. While changes in re-alignment and mechanical properties have been investigated recently during development, they have not been studied in (1) aged tendons, or (2) in the absence of key proteoglycans. Collagen fiber re-alignment and the corresponding mechanical properties are quantified throughout tensile mechanical testing in both the insertion site and the midsubstance of mouse supraspinatus tendons in wild type (WT), decorin-null (Dcn(-/-)), and biglycan-null (Bgn(-/-)) mice at three different ages (90 days, 300 days, and 570 days). Percent relaxation was significantly decreased with age in the WT and Dcn(-/-) tendons, but not in the Bgn(-/-) tendons. Changes with age were found in the linear modulus at the insertion site where the 300 day group was greater than the 90 day and 570 day group in the Bgn(-/-) tendons and the 90 day group was smaller than the 300 day and 570 day groups in the Dcn(-/-) tendons. However, no changes in modulus were found across age in WT tendons were found. The midsubstance fibers of the WT and Bgn(-/-) tendons were initially less aligned with increasing age. The re-alignment was significantly altered with age in the WT tendons, with older groups responding to load later in the mechanical test. This was also seen in the Dcn(-/-) midsubstance and the Bgn(-/-) insertion, but not in the other locations. Although some studies have found changes in the WT mechanical properties with age, this study did not support those findings. However, it did show fiber re-alignment changes at both locations with age, suggesting a breakdown of tendon's ability to respond to load in later ages. In the proteoglycan-null tendons however, there were changes in the mechanical properties, accompanied only by location-dependent re-alignment changes, suggesting a site-specific role for these molecules in loading. Finally, changes in the mechanical properties did not occur in concert with changes in re-alignment, suggesting that typical mechanical property measurements alone are insufficient to describe how structural alterations affect tendon's response to load.

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Section: Days 300 Days 570 Dayssupporting

confidence: 87%

Effect of Age and Proteoglycan Deficiency on Collagen Fiber Re-Alignment and Mechanical Properties in Mouse Supraspinatus Tendon

Connizzo¹,

Sarver

Iozzo

et al. 2013

Journal of Biomechanical Engineering

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“…109 These proteins do not provide the same stiffness of collagen; however, they are highly polar and attract water, which serves as a lubricnt cushion to absorb compressive stresses in the tissue. 110 In addition, proteoglycans and GAGs can help sequester, or function as coligands, for growth factors. 95 In CAVD, proteoglycans and GAGs might contribute to atherosclerotic lesion development by retaining lipids accumulation and attraction inflammatory cells in the valve ECM.…”

Section: The Extracellular Matrixmentioning

confidence: 99%

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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“…It is observed that chemically crosslinking pericardium damages and distorts the natural structure, destroys interstitial cells, and diminishes potential for viable cell inhabitation. 13 The specialized matrix consisting of collagen, elastin, and glycosaminoglycans (GAGS) that compose the pericardium is responsible for allowing the tissue to accommodate the constant changes in shape and stress transfer, 13,14 and is therefore essential to maintain. Damaging this natural structure and removing native cells results in a tissue that can no longer maintain or repair itself.…”

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confidence: 99%