Pulmonary elastic tissue in generalized elastolysis (cutis laxa) and marfan's syndrome. A light and electron microscopic study

Sayers, C. Paul; Goltz, Robert W.; Mottaz, Jess H.

doi:10.1111/1523-1747.ep12608193

Cited by 45 publications

(18 citation statements)

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“…Fragmented elastic fibers, with a granular appearance, and microfibrils were noticed. 26 In another study, four out of four infants with Marfan syndrome had microscopic emphysema similar to that observed in older patients with emphysema but without Marfan syndrome. 19 In yet another study, four out of four infants with Marfan syndrome had microscopical features of emphysema, with interrupted, fragmented, and clumped fibers that were not observed in 13 control infants.…”

Section: Discussionmentioning

confidence: 61%

“…In man, developmental emphysema has been noticed in patients with Marfan syndrome, an autosomal disorder caused by mutations in the gene encoding fibrillin-1. [19][20][21][22][23][24][25][26][27] In mice, disruption of the fibrillin-1 gene results in developmental emphysema. The tight skin mouse, characterized by tandem duplication of 30-40 kb in the gene encoding fibrillin-1, develops emphysematous lesions that are in many ways similar to those observed in humans.…”

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confidence: 99%

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Aberrant fibrillin-1 expression in early emphysematous human lung: a proposed predisposition for emphysema

et al. 2008

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Parenchymal destruction, airspace enlargement, and loss of elasticity are hallmarks of pulmonary emphysema. Although the basic mechanism is unknown, there is a consensus that malfunctioning of the extracellular matrix is a major contributor to the pathogenesis of emphysema. In this study, we analyzed the expression of the elastic fiber protein fibrillin-1 in a large number (n ¼ 69) of human lung specimens with early-onset emphysema. Specimens were morphologically characterized by the Destructive Index, the Mean Linear Intercept, and the Panel Grading. We observed a strong correlation (Po0.001) of aberrant fibrillin-1 staining with the degree of destruction of lung parenchyma (r ¼ 0.71), airspace enlargement (r ¼ 0.47), and emphysema-related morphological abnormalities (r ¼ 0.69). There were no obvious correlations with age and smoking behavior. Staining for three other extracellular matrix components (type I collagen, type IV collagen, and laminin) was not affected. The aberrant fibrillin-1 staining observed in this study is similar to that observed in Marfan syndrome, a syndrome caused by mutations in the gene encoding fibrillin-1. Strikingly, emphysema is noticed in a number of Marfan patients. This, together with the notion that disruption of the fibrillin-1 gene in mice results in emphysematous lesions, makes fibrillin-1 a strong candidate to be involved in the etiology and pathogenesis of emphysema.

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Section: Discussionmentioning

confidence: 61%

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confidence: 99%

Aberrant fibrillin-1 expression in early emphysematous human lung: a proposed predisposition for emphysema

et al. 2008

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“…These types of investigations have not been performed in patients with Marfan syndrome. However, previous reports have identified emphysematous changes of varying severity in histopathologic examination of lung biopsy and autopsy specimens from patients with Marfan syndrome [20,21,22]. Aberrant fibrillin-1 expression was recently implicated in the pathogenesis of early emphysema in humans [23].…”

Section: Discussionmentioning

confidence: 99%

Pneumothorax and Bullae in Marfan Syndrome

Karpman¹,

Aughenbaugh²,

Ryu

2011

Respiration

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Background: Increased risk of spontaneous pneumothorax has been described in patients with Marfan syndrome and has been attributed, in part, to the presence of apical blebs and bullae. Objectives: We assess the risk of pneumothorax and its relationship to the presence of apical blebs and bullae in patients with Marfan syndrome in the era of CT imaging. Methods: A retrospective cohort study was performed of all patients 13 years or older with Marfan syndrome evaluated at the Mayo Clinic, Rochester, Minn., USA, from 1998 through 2008. One hundred and sixty-six patients met the current diagnostic criteria for Marfan syndrome and had chest imaging studies available for review. Results: The median age was 40 years (range 14–71); 37% had a smoking history. Eight of 166 patients (4.8%) had experienced 1 or more episodes of spontaneous pneumothorax, and 2 of these 8 patients had 2 or more episodes. Apical blebs or bullae were identified on radiologic imaging in 16 patients (9.6%). Four of 16 (25%) patients with apical blebs or bullae had a history of spontaneous pneumothorax compared to 4 of 150 patients (2.7%) without blebs or bullae (p = 0.003). Conclusions: The frequency of blebs is relatively low in patients with Marfan syndrome but the risk of pneumothorax is significantly higher in those with radiologically detectable blebs or bullae. Chest CT scanning to identify blebs and bullae may allow risk stratification for pneumothorax in patients with Marfan syndrome.

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“…Histologically, elastic fibres in the emphysematous lung appear fragmented, with a reduced microfibrillar component and evidence of disorganised elastin deposition (Fukuda et al 1989). Evidence for the involvement of fibrillin in the pathogenesis of emphysema comes from the observation of emphysematous lesions in connective tissues disorders such as neonatal (Jacobs et al 2002;Milewicz and Duvic 1994) and adult (Bolande and Tucker 1964;Sayers et al 1975) Marfan syndrome and the tight skin mouse model of hereditary emphysema (Gardi et al 1989). Whilst even in the early stages of human emphysema fragmentation of fibrillin microfibril bundles is evident (Robbesom et al 2008).…”

Section: Pulmonarymentioning

confidence: 99%

Tissue elasticity and the ageing elastic fibre

Sherratt

2009

AGE

265

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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Pulmonary elastic tissue in generalized elastolysis (cutis laxa) and marfan's syndrome. A light and electron microscopic study

Cited by 45 publications

References 4 publications

Aberrant fibrillin-1 expression in early emphysematous human lung: a proposed predisposition for emphysema

Aberrant fibrillin-1 expression in early emphysematous human lung: a proposed predisposition for emphysema

Pneumothorax and Bullae in Marfan Syndrome

Tissue elasticity and the ageing elastic fibre

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