Detection of remnant proteolytic activities in unimplanted glutaraldehyde‐treated bovine pericardium and explanted cardiac bioprostheses

Simionescu, Dan T.; Simionescu, Anca A.; Deac, Radu

doi:10.1002/jbm.820270615

Cited by 25 publications

(19 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both MMP-2 and MMP-9 were shown to be involved in the progression of atherosclerotic plaque 8 and in calcification of glutaraldehyde fixed heterograft bioprosthetic heart valves. 15 In our cell culture studies using AVICs cultured on a collagen gel in the presence of TN-C, we observed a seven-to eightfold increase in MMP-2 mRNA expression ( Figure 3A), and the gelatinolytic activity of MMP-2 was also increased ( Figure 3B), which suggests that the accumulation of TN-C around calcific regions may up-regulate the expression of MMP-2. The fact that most of the secreted MMP-2 (in conditioned medium) was in the pro form, and the active form of MMP-2 was associated with cells in cell lysates ( Figure 3B) may help explain our observations in the clinical aortic valve retrievals, that most MMP-2 was in its pro form (Figure 2).…”

Section: Discussionmentioning

confidence: 76%

“…[15][16][17] In addition, it has been demonstrated, in vascular smooth muscle cells, that degradation of type I collagen by MMPs promotes TN-C expression at the transcriptional level. 18 Conversely, TN-C also up-regulates the expression of MMPs.…”

mentioning

confidence: 99%

“…19 These findings are noteworthy because MMP-2 and MMP-9 expression/activity are associated with calcification of glutaraldehyde fixed heterograft bioprosthetic heart valves. 15 Recently, MMP-1, MMP-2, and MMP-9 were demonstrated to be present in calcific aortic stenosis cusps. 20 Our hypothesis focused on the relationship between TN-C and MMP-2.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Matrix Metalloproteinase-2 Is Associated with Tenascin-C in Calcific Aortic Stenosis

Jiang

Jones

et al. 2001

The American Journal of Pathology

153

100

View full text Add to dashboard Cite

We previously showed that the expression of tenascin (TN-C), an extracellular matrix glycoprotein found in developing bone and atherosclerotic plaque, and ma- The mechanism of calcific aortic stenosis has been investigated in clinical-pathological studies, that have demonstrated cuspal calcific deposits to be associated with mineralization of devitalized cells and subcellular vesicles, 1,2 as well as the deposition of extracellular matrix (ECM) proteins commonly present in bone.3 A number of ECM proteins normally found in bone, including osteocalcin, osteopontin, osteonectin, matrix Gla protein, bone morphogenetic protein, matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9, are present in cardiovascular calcifications, including calcified valves, 3-9 but in general are not found in normal cardiovascular tissue. Bone morphogenetic protein-2 was also found in a cultured calcifying subpopulation of bovine aortic smooth muscle cells, 7 and calcifying aortic valve interstitial cells.10

show abstract

Section: Discussionmentioning

confidence: 76%

mentioning

confidence: 99%

See 1 more Smart Citation

Matrix Metalloproteinase-2 Is Associated with Tenascin-C in Calcific Aortic Stenosis

Jiang

Jones

et al. 2001

The American Journal of Pathology

153

100

View full text Add to dashboard Cite

show abstract

“…Proteases that cause structural collagen damage in other cardiovascular tissues 35,36 have been identified in pericardial heart valves. 37 However, the nature of in vivo structural defects identified in the present study and the substantial correlation with in vitro studies and others discussed below suggest that the mechanical effects dominate in the degradation of the extracellular matrix.…”

Section: Mechanisms Of Noncalcific Damagementioning

confidence: 72%

Collagen fiber disruption occurs independent of calcification in clinically explanted bioprosthetic heart valves

Sacks

Schoen

2002

J. Biomed. Mater. Res.

156

103

View full text Add to dashboard Cite

The durability of bioprosthetic heart valves (BHV) is severely limited by tissue deterioration, manifested as calcification and mechanical damage to the extracellular matrix. Extensive research on mineralization mechanisms has led to prevention strategies, but little work has been done on understanding the mechanisms of noncalcific matrix damage. The present study tested the hypothesis that calcification-independent damage to the valvular structural matrix mediated by mechanical factors occurs in clinical implants and could contribute to porcine aortic BHV structural failure. We correlated quantitative assessment of collagen fiber orientation and structural integrity by small angle light scattering (SALS) with morphologic analysis in 14 porcine aortic valve bioprostheses removed from patients for structural deterioration following 5-20 years of function. Calcification of the explants varied from 0 (none) to 1+ (minimal) to 4+ (extensive), as assessed radiographically. SALS tests were performed over entire excised cusps using a 0.254-mm spaced grid, and the resultant structural information used to generate maps of the local collagen fiber damage that were compared with sites of calcific deposits. All 42 cusps showed clear evidence of substantial noncalcific structural damage. In 29 cusps that were calcified, structural damage was consistently spatially distinct from the calcification deposits, generally in a distribution similar to that noted in porcine BHV subjected to in vitro durability testing. Our results suggest a mechanism of noncalcific degradation dependent on cuspal mechanics that could contribute to porcine aortic BHV failure.

show abstract

“…13,14 For example, subdermally implanted glutaraldehyde-treated bovine parietal pericardium contains an array of extracellular matrix protein-degrading proteinases including serine proteinases and MMPs. 13,14 High concentrations of MMPs are also present in atherosclerotic plaques 15 and in restenotic lesions. 16 Tenascin-C (TN-C) is an extracellular matrix glycoprotein with a highly restricted pattern of gene expression, but it is prominently expressed in embryonic and adult tissues that are actively remodeling.…”

mentioning

confidence: 99%

Inhibition of Matrix Metalloproteinase Activity Attenuates Tenascin-C Production and Calcification of Implanted Purified Elastin in Rats

Vyavahare

Jones

Tallapragada

et al. 2000

The American Journal of Pathology

View full text Add to dashboard Cite

Elastin, a major extracellular matrix protein present in arterial walls provides elastic recoil and resilience to arteries. Elastin is prone to calcification in a number of cardiovascular diseases including atherosclerosis and bioprosthetic heart valve mineralization. We have recently shown that purified elastin when implanted subdermally in rats undergoes severe calcification. In the present study, we used this elastin implant model to investigate the molecular mechanisms underlying elastin calcification. Intense matrix metalloproteinase (MMP-2) and tenascin-C (TN-C) expression were seen in the proximity of the initial calcific deposits at 7 days. Gelatin zymography studies showed both MMP-2 (latent and active form) and MMP-9 expression within the implants. To investigate the role of MMPs in calcification, rats were adminis- Elastin is an extracellular matrix protein present in a variety of tissues including the arterial wall and heart valves. 1 Pathological calcification of elastin occurs in a number of disease processes including atherosclerosis, cardiac valve disease, and bioprosthetic heart valve calcification. [2][3][4] Despite the importance of elastin calcification in cardiovascular disease, the mechanisms underlying this process are not fully understood. We recently characterized a rat subdermal implant model to study calcification of purified elastin. 5 Explants from these animals showed deposition of poorly crystalline hydroxyapatite on implanted elastin fibers, comparable to pathological cardiovascular calcification. 5 This system is therefore useful for determining the cellular and molecular mechanisms leading to elastin-oriented calcification.Although the elastic fibers can be considered physiologically inert during adult life, a wide range of insults to elastic tissue can result in either chronic loss or excess accumulation. 6 Matrix metalloproteinases (MMPs) are involved in elastolysis. In particular, both MMP-2 and MMP-9 are known to bind to insoluble elastin, 7 and each has been shown to be actively involved in elastin degradation. 8,9 Exuberant production of MMPs is a hallmark of many destructive diseases, such as arthritis, chronic ulceration, and tumor formation. 10 -12 With respect to calcification, MMPs have also been detected in association with calcification of bioprostheses. 13,14 For example, subdermally implanted glutaraldehyde-treated bovine parietal pericardium contains an array of extracellular matrix protein-degrading proteinases including serine proteinases and MMPs. 13,14 High concentrations of MMPs are also present in atherosclerotic plaques 15 and in restenotic lesions. 16

show abstract

Detection of remnant proteolytic activities in unimplanted glutaraldehyde‐treated bovine pericardium and explanted cardiac bioprostheses

Cited by 25 publications

References 37 publications

Matrix Metalloproteinase-2 Is Associated with Tenascin-C in Calcific Aortic Stenosis

Matrix Metalloproteinase-2 Is Associated with Tenascin-C in Calcific Aortic Stenosis

Collagen fiber disruption occurs independent of calcification in clinically explanted bioprosthetic heart valves

Inhibition of Matrix Metalloproteinase Activity Attenuates Tenascin-C Production and Calcification of Implanted Purified Elastin in Rats

Contact Info

Product

Resources

About