Nitrite-induced cross-linking alters remodeling and mechanical properties of collagenous engineered tissues.

Abstract:

:Cumulative damage to long-lived connective tissue proteins play a key role in the development of age-related human diseases such as cardiovascular stiffening and age-related macular degeneration. The processes that result in the accumulation of increasingly insoluble, undigestible damaged collagen are only partially known. Nonenzymatic glycation (NEG) is one such process and has been linked to the development of diabetic-related complications and aging. An additional novel mechanism particularly relevant to smoking- and inflammation-related diseases involves the nonenzymatic nitrite (NEN) modification of connective tissue proteins. The present study was undertaken to examine the effects of NEN of fibrillar type I collagen on cell-mediated remodeling and mechanical properties of collagenous tissues. Using a modification of an in vitro fibroblast-populated collagen gel model system developed in our laboratory, we tested two hypotheses: NEN reduces the ability of primary adult cardiac fibroblasts to remodel type I collagen gels; NEN reduces the deformability of type I collagen gels subjected to mechanical testing. The results show that NEN impairs both cell-mediated remodeling and mechanical deformability in collagenous engineered tissues. Furthermore, these mechanical changes correlate with the degree of cross-linking as determined by SDS-PAGE. Thus, we concluded that NEN reactions may contribute to alterations in the biomechanical properties of collagen-containing tissues consistent with the age-related functional decline observed in human disease.

journal_name

Connect Tissue Res

authors

Paik DC,Saito LY,Sugirtharaj DD,Holmes JW

doi

10.1080/03008200600721569

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

163-76

issue

3

eissn

0300-8207

issn

1607-8438

pii

N47068UV6322VV80

journal_volume

47

pub_type

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