Smooth muscle cell depletion and collagen types in progeric arteries

Stehbens, William E.; Delahunt, Brett; Shozawa, Takeshi; Gilbert‐Barness, Enid

doi:10.1016/s1054-8807(01)00069-2

Cited by 112 publications

(115 citation statements)

References 11 publications

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“…As a consequence there is premature loss of functional 'young' cells and a concomitant premature accumulation of senescent cells, both of which promote the age-related decline in tissue function leading to premature senescence of the individual. Indeed, post-mortem studies have shown that progeric arteries are depleted of smooth muscle cells, which is consistent with atherosclerotic disease (Stehbens et al, 2001).…”

Section: Discussionmentioning

confidence: 57%

Aging of Hutchinson–Gilford progeria syndrome fibroblasts is characterised by hyperproliferation and increased apoptosis

Bridger

Kill

2004

Experimental Gerontology

157

137

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Hutchinson -Gilford progeria syndrome is a rare genetic disorder that mimics certain aspects of aging prematurely. Recent work has revealed that mutations in the lamin A gene are a cause of the disease. We show here that cellular aging of Hutchinson -Gilford progeria syndrome fibroblasts is characterised by a period of hyperproliferation and terminates with a large increase in the rate of apoptosis. The occurrence of cells with abnormal nuclear morphology reported by others is shown to be a result of cell division since the fraction of these abnormalities increases with cellular age. Similarly, the proportion of cells with an abnormal or absent A-type lamina increases with age. These data provide clues as to the cellular basis for premature aging in HGPS and support the view that cellular senescence and tissue homeostasis are important factors in the normal aging process. q 2004 Elsevier Inc. All rights reserved.

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Section: Discussionmentioning

confidence: 57%

Aging of Hutchinson–Gilford progeria syndrome fibroblasts is characterised by hyperproliferation and increased apoptosis

Bridger

Kill

2004

Experimental Gerontology

157

137

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“…The transgenic mice did not manifest any of the early hallmarks of progeria, such as retarded growth or bone disease, nor did they exhibit atherosclerotic lesions in the intima layer of large vessels. However, they did show a loss of smooth muscle cells in the media of the aorta, a feature noted in the autopsies of some progeric patients [46].…”

Section: The A-type Laminopathiesmentioning

confidence: 82%

“…The average age of death in HGPS is 12 to 15 years, usually due to artherosclerosis resulting in myocardial infarction or stroke [44]. Artherosclerosis in the HGPS patients does not appear to be linked to abnormal systemic lipid levels [45], but might be linked to smooth muscle depletion in atherosclerotic aortas [46]. Also, HGPS individuals do not show any increase in tumor susceptibility, cataract formation, or cognitive degeneration, features often associated with normal aging.…”

Section: The A-type Laminopathiesmentioning

confidence: 99%

Mouse models of the laminopathies

Stewart

Kozlov

Fong

et al. 2007

Experimental Cell Research

107

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The A and B type lamins are nuclear intermediate filament proteins that comprise the bulk of the nuclear lamina, a thin proteinaceous structure underlying the inner nuclear membrane. The A-type lamins are encoded by the lamin A gene (LMNA). Mutations in this gene have been linked to at least nine diseases, including the progeroid diseases Hutchinson-Gilford progeria and atypical Werner's syndromes, striated muscle diseases including muscular dystrophies and dilated cardiomyopathies, lipodystrophies affecting adipose tissue deposition, diseases affecting skeletal development, and a peripheral neuropathy. To understand how different diseases arise from different mutations in the same gene, mouse lines carrying some of the same mutations found in the human diseases have been established. We, and others have generated mice with different mutations that result in progeria, muscular dystrophy, and dilated cardiomyopathy. To further our understanding of the functions of the lamins, we also created mice lacking lamin B1, as well as mice expressing only one of the Atype lamins. These mouse lines are providing insights into the functions of the lamina and how changes to the lamina affect the mechanical integrity of the nucleus as well as signaling pathways that, when disrupted, may contribute to the disease.

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“…Moreover, unlike common forms of atherosclerosis, type I collagen has been shown to be dramatically reduced in the arterial adventitia and media and in both external and internal basement membranes of HGPS patients. Additionally, type I collagen is overrepresented in the arterial intimas of these patients [22]. Type III collagen is distributed in all three layers of arterial wall, as seen in control arteries [22].…”

Section: Introductionmentioning

confidence: 78%

“…Additionally, type I collagen is overrepresented in the arterial intimas of these patients [22]. Type III collagen is distributed in all three layers of arterial wall, as seen in control arteries [22]. Microarray studies of HPGS fibroblasts have so far failed to elucidate the pathogenesis [23,24].…”

Section: Introductionmentioning

confidence: 98%

Collagen expression in fibroblasts with a novel LMNA mutation

Nguyen

Leistritz

Turner

et al. 2007

Biochemical and Biophysical Research Communications

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Laminopathies are a group of genetic disorders caused by LMNA mutations; they include muscular dystrophies, lipodystrophies and progeroid syndromes. We identified a novel heterozygous LMNA mutation, L59R, in a patient with the general appearance of mandibuloacral dysplasia and progeroid features. Examination of the nuclei of dermal fibroblasts revealed the irregular morphology characteristic of LMNA mutant cells. The nuclear morphological abnormalities of LMNA mutant lymphoblastoid cell lines were less prominent compared to those of primary fibroblasts. Since it has been reported that progeroid features are associated with increased extracellular matrix in dermal tissues, we compared a subset of these components in fibroblast cultures from LMNA mutants with those of control fibroblasts. There was no evidence of intracellular accumulation or altered mobility of collagen chains, or altered conversion of procollagen to collagen, suggesting that skin fibroblastmediated matrix production may not play a significant role in the pathogenesis of this particular laminopathy.

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Smooth muscle cell depletion and collagen types in progeric arteries

Cited by 112 publications

References 11 publications

Aging of Hutchinson–Gilford progeria syndrome fibroblasts is characterised by hyperproliferation and increased apoptosis

Aging of Hutchinson–Gilford progeria syndrome fibroblasts is characterised by hyperproliferation and increased apoptosis

Mouse models of the laminopathies

Collagen expression in fibroblasts with a novel LMNA mutation

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