Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon.

Shapiro, Steve D.; Endicott, Scott K.; Province, Michael A.; Pierce, John A.; Campbell, Edward J.

doi:10.1172/jci115204

Cited by 576 publications

(396 citation statements)

References 52 publications

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“…Modifications in the levels and ratios of these proteins (among others) thus alter relative contributions of each molecule to ECM stiffness. Homeostatic turnover of these proteins is markedly different, with collagen fibers estimated to undergo remodeling at a rate of 3 to 10% per day (25), whereas elastin fibers are long lived, with a mean stability of 74 years in humans (26). In disease, these rates likely vary, although data are sparse in humans.…”

Section: Modulation Of Ecm Stiffnessmentioning

confidence: 99%

Lung Extracellular Matrix and Fibroblast Function

2015

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Extracellular matrix (ECM) is a tissue-specific macromolecular structure that provides physical support to tissues and is essential for normal organ function. In the lung, ECM plays an active role in shaping cell behavior both in health and disease by virtue of the contextual clues it imparts to cells. Qualities including dimensionality, molecular composition, and intrinsic stiffness all promote normal function of the lung ECM. Alterations in composition and/or modulation of stiffness of the focally injured or diseased lung ECM microenvironment plays a part in reparative processes performed by fibroblasts. Under conditions of remodeling or in disease states, inhomogeneous stiffening (or softening) of the pathologic ECM may both precede modifications in cell behavior and be a result of disease progression. The ability of ECM to stimulate further ECM production by fibroblasts and drive disease progression has potentially significant implications for mesenchymal stromal cell-based therapies; in the setting of pathologic ECM stiffness or composition, the therapeutic intent of progenitor cells may be subverted. Taken together, current data suggest that lung ECM actively contributes to health and disease; thus, mediators of cell-ECM signaling or factors that influence ECM stiffness may represent viable therapeutic targets in many lung disorders.

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Section: Modulation Of Ecm Stiffnessmentioning

confidence: 99%

Lung Extracellular Matrix and Fibroblast Function

2015

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“…AAR studies in humans indicate that aortic elastin is much more metabolically stable than the fibrillar collagens (Powell et al 1992) and that elastin in skin, although not replaced, may undergo age-related damage (Ritz-Timme et al 2003). The most compelling evidence for elastic fibre longevity in a human tissue was presented by Shapiro and coworkers (Shapiro et al 1991). Using AAR techniques in combination with mass-spectrometry to assess incorporation of 14 C into both the elastin and glycoprotein (fibrillin microfibril) fractions, this study demonstrated that the age of elastic fibres in the lung corresponded to the age of the individual.…”

Section: Structure and Functionmentioning

confidence: 99%

“…This bound calcium may also play a role in mediating the uptake of lipids by elastic fibres in the ageing arterial wall (for a review see Robert et al 2008). In addition to binding extracellular ions and biomolecules, L-forms of aspartic acid within elastic fibre proteins spontaneously convert to D-forms at a predictable rate (Shapiro et al 1991). Both elastin and fibrillin accumulate D-aspartic acid by aspartic acid racemization, but the consequences for the structure and function of the ageing elastic fibre remain poorly defined (Bailey 2001).…”

Section: Degradationmentioning

confidence: 99%

Tissue elasticity and the ageing elastic fibre

Sherratt

2009

AGE

269

189

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The ability of elastic tissues to deform under physiological forces and to subsequently release stored energy to drive passive recoil is vital to the function of many dynamic tissues. Within vertebrates, elastic fibres allow arteries and lungs to expand and contract, thus controlling variations in blood pressure and returning the pulmonary system to a resting state. Elastic fibres are composite structures composed of a cross-linked elastin core and an outer layer of fibrillin microfibrils. These two components perform distinct roles; elastin stores energy and drives passive recoil, whilst fibrillin microfibrils direct elastogenesis, mediate cell signalling, maintain tissue homeostasis via TGFβ sequestration and potentially act to reinforce the elastic fibre. In many tissues reduced elasticity, as a result of compromised elastic fibre function, becomes increasingly prevalent with age and contributes significantly to the burden of human morbidity and mortality. This review considers how the unique molecular structure, tissue distribution and longevity of elastic fibres pre-disposes these abundant extracellular matrix structures to the accumulation of damage in ageing dermal, pulmonary and vascular tissues. As compromised elasticity is a common feature of ageing dynamic tissues, the development of strategies to prevent, limit or reverse this loss of function will play a key role in reducing age-related morbidity and mortality.

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“…These layers of elastin are essential for the normal compliance of the aorta, allowing it to accommodate the high volume of blood during systole and the elastic recoil during diastole, which maintains an even forward flow of blood to the body against a closed aortic valve. Elastin has a very low turnover because its half-life is ~40 y (30), and the number of elastin lamellar units in a particular vascular segment does not change after birth.…”

Section: Aortic Structure and Compositionmentioning

confidence: 99%

Preterm birth with antenatal corticosteroid administration has injurious and persistent effects on the structure and composition of the aorta and pulmonary artery

et al. 2011

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INTRODUCTION:Preterm birth affects 8-12% of live births and is associated with the development of elevated arterial blood pressure and aortic narrowing in later life; this suggests that preterm birth may alter the development of arteries. Our objective was to determine the effects of preterm birth, accompanied by antenatal corticosteroid administration, on the structure of the aorta and pulmonary artery, which experience different alterations in pressure flow at birth. RESULTS: at 11 wk, preterm lambs had significantly thicker aortic walls and a smaller lumen, whereas the morphometry of the pulmonary artery was unaffected. elastin deposition was markedly increased in the aorta and pulmonary artery and smooth muscle content was reduced in the aorta only. In preterm lambs we found injury in the aorta only; controls were unaffected. DISCUSSION: We conclude that moderate preterm birth after antenatal betamethasone can cause injury and persistent alterations in the structure and composition of the aorta, with lesser effects in the pulmonary artery. Our findings suggest that preterm birth may increase the risk of atherosclerosis and aortic aneurysms in later life. METHODS:Using an established ovine model of preterm birth, lambs were born at 0.9 of gestation and underwent necropsy at 11 wk after birth; controls were born at term.

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Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon.

Cited by 576 publications

References 52 publications

Lung Extracellular Matrix and Fibroblast Function

Lung Extracellular Matrix and Fibroblast Function

Tissue elasticity and the ageing elastic fibre

Preterm birth with antenatal corticosteroid administration has injurious and persistent effects on the structure and composition of the aorta and pulmonary artery

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