Aortic disease is a significant cause of death in developed countries. The most common forms of aortic disease are aneurysm, dissection, atherosclerotic occlusion and ageing-induced stiffening. The microstructure of the aortic tissue has been studied with great interest, because alteration of the quantity and/or architecture of the connective fibres (elastin and collagen) within the aortic wall, which directly imparts elasticity and strength, can lead to the mechanical and functional changes associated with these conditions. This review article summarizes the state of the art with respect to characterization of connective fibre microstructure in the wall of the human aorta in ageing and disease, with emphasis on the ascending thoracic aorta and abdominal aorta where the most common forms of aortic disease tend to occur.

https://royalsocietypublishing.org/doi/pdf/10.1098/rsif.2012.1004

Elastin and collagen fibre microstructure of the human aorta in ageing and disease: a review

Aged human skin is fragile because of fragmentation and loss of type I collagen fibrils, which confer strength and resiliency. We report here that dermal fibroblasts express increased levels of collagen-degrading matrix metalloproteinases-1 (MMP-1) in aged (>80 years old) compared with young (21 to 30 years old) human skin in vivo. Transcription factor AP-1 and α2β1 integrin, which are key regulators of MMP-1 expression, are also elevated in fibroblasts in aged human skin in vivo. MMP-1 treatment of young skin in organ culture causes fragmentation of collagen fibrils and reduces fibroblast stretch, consistent with reduced mechanical tension, as observed in aged human skin. Limited fragmentation of three-dimensional collagen lattices with exogenous MMP-1 also reduces fibroblast stretch and mechanical tension. Furthermore, fibroblasts cultured in fragmented collagen lattices express elevated levels of MMP-1, AP-1, and α2β1 integrin. Importantly, culture in fragmented collagen raises intracellular oxidant levels and treatment with antioxidant MitoQ10 significantly reduces MMP-1 expression. These data identify positive feedback regulation that couples age-dependent MMP-1-catalyzed collagen fragmentation and oxidative stress. We propose that this self perpetuating cycle promotes human skin aging. These data extend the current understanding of the oxidative theory of aging beyond a cellular-centric view to include extracellular matrix and the critical role that connective tissue microenvironment plays in the biology of aging.

/pdf/collagen-fragmentation-promotes-oxidative-stress-and-dk3zvkbx5r.pdf

Collagen fragmentation promotes oxidative stress and elevates matrix metalloproteinase-1 in fibroblasts in aged human skin.

A strain energy function for arteries accounting for wall composition and structure

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.

/pdf/tissue-elasticity-and-the-ageing-elastic-fibre-3mcje9j7yn.pdf

Tissue elasticity and the ageing elastic fibre

The lung is composed of airways and lung parenchyma, and the extracellular matrix (ECM) contains the main building blocks of both components. The ECM provides physical support and stability to the lung, and as such it has in the past been regarded as an inert structure. More recent research has provided novel insights revealing that the ECM is also a bioactive environment that orchestrates the cellular responses in its environs. Changes in the ECM in the airway or parenchymal tissues are now recognized in the pathological profiles of many respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Only recently have we begun to investigate whether these ECM changes result from the disease process, or whether they constitute a driving factor that orchestrates the pathological outcomes. This review summarizes our current knowledge of the alterations in the ECM in asthma, COPD, and IPF, and the contributions of these alterations to the pathologies. Emerging data suggest that alterations in the composition, folding or rigidity of ECM proteins may alter the functional responses of cells within their environs, and in so doing change the pathological outcomes. These characteristics highlight potential avenues for targeting lung pathologies in the future. This may ultimately contribute to a better understanding of chronic lung diseases, and novel approaches for finding therapeutic solutions. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

/pdf/the-extracellular-matrix-the-under-recognized-element-in-x6fk695yc4.pdf

The extracellular matrix - the under-recognized element in lung disease?

The biochemical analysis of samples of aortic connective tissue was carried out in 22 subjects from 9 to 84 years old.Aortic samples were taken at necropsy performed after sudden or, more often, traumatic death. The results suggest that aging of the aorta is accompanied by an increase both in collagen content and in total sugar content when expressed as mg/cm2 while the elastin content, when expressed in the same way, does not undergo any variation.

Aortic Connective Tissue in Ageing—A Biochemical Study

Collagen, elastin and structural glycoproteins were measured in 21 intact lungs taken at postmortem examination after sudden death from subjects aged from 15 to 83. The data were expressed as milligrams per cubic centimeter of lung peripheral parenchyma inflated and fixed at the standard pressure of 25 cm H2O to exclude the pitfall of referring to dried tissue weight. The volume/weight ratio of inflated dried lung parenchyma increased significantly with aging; likewise the collagen content decreased and so did the collagen/elastin ratio, while the elastin content did not show any significant correlation with age. The present findings indicate that biochemical, morphological and functional data on the senile lung agree well.

Connective tissue in aging lung.

Biochemical analysis of dermal connective tissue was carried out in 14 sub jects affected by primary uncomplicated varicose veins and 14 controls. Skin samples were taken, according to fixed criteria, from operation pieces of total mastectomy for breast cancer.The results suggest that the dermal tissue in these subjects is just thinner than that of controls, confirming previous similar clinical findings.The elective reduction of the collagen content observed, unassociated with changes of other components of the dermal connective tissue, brings evidence for a systemic biochemical defect of the extracellular matrix i.e. a collagen de fect affecting the entire body structure and not only the varicose or pre-varicose veins of the lower limbs.

Salvatore Sampognaro

Papers

Aortic Connective Tissue in Ageing—A Biochemical Study

Connective tissue in aging lung.

Biochemical analysis of dermal connective tissue in subjects affected by primary uncomplicated varicose veins.

Contents, Vol. 29, 1983