Histological and Ultrastructural Features of Atherosclerosis in Progeria

Stehbens, William E.; Wakefield, St. John; Gilbert‐Barness, Enid; Olson, Robert E.; Ackerman, Jeanne

doi:10.1016/s1054-8807(98)00023-4

Cited by 126 publications

(111 citation statements)

References 35 publications

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“…For instance, Stehbens et al suggested that the xanthomatous vascular lesions that are typical for homozygous FH are not seen in the atherosclerosis of HGPS. 47,48 Furthermore, serum lipoproteins in HGPS are relatively normal, except for occasional reports of depressed HDL cholesterol. 38 Exposure to risk factors such as poor diet, smoking, or hypertension is an unlikely proatherogenic mechanism in HGPS.…”

Section: Atherosclerosis In Hgpsmentioning

confidence: 99%

“…For instance, endothelial cells with mutant LMNA might not regenerate fully to restore intimal integrity after injury. 30 Also, vascular smooth muscle cells in HGPS were susceptible to hemodynamic and ischemic stress injury 47 and were depleted from arterial media. 48 An alternative proposed mechanism for atherosclerosis in HGPS is hyperhyaluronic acidemia and aciduria, 56,57 which are suggested to cause vascular calcification 58 despite the fact that these biochemical abnormalities are not specific for either HGPS or atherosclerosis.…”

Section: Atherosclerosis In Hgpsmentioning

confidence: 99%

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Laminopathies and Atherosclerosis

Alshali

Hegele

2004

ATVB

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Abstract-Laminopathies are genetic diseases that encompass a wide spectrum of phenotypes with diverse tissue pathologies and result mainly from mutations in the LMNA gene encoding nuclear lamin A/C. Some laminopathies affect the cardiovascular system, and a few (namely, Dunnigan-type familial partial lipodystrophy [FPLD2] and HutchinsonGilford progeria syndrome [HGPS]) feature atherosclerosis as a key component. The premature atherosclerosis of FPLD2 is probably related to characteristic proatherogenic metabolic disturbances such as dyslipidemia, hyperinsulinemia, hypertension, and diabetes. In contrast, the premature atherosclerosis of HGPS occurs with less exposure to metabolic proatherogenic traits and probably reflects the generalized process of accelerated aging in HGPS. Although some common polymorphisms of LMNA have been associated with traits related to atherosclerosis, the monogenic diseases Key Words: nuclear envelope Ⅲ insulin resistance Ⅲ aging Ⅲ vascular disease Ⅲ progeria T he nuclear lamina is a 20-nm filamentous meshwork that underlies the inner nuclear membrane and plays a central role in defining interphase nuclear architecture, DNA replication, and chromatin organization. 1 Nuclear lamins are type V intermediate filaments that are the major components of the nuclear lamina.

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Section: Atherosclerosis In Hgpsmentioning

confidence: 99%

Section: Atherosclerosis In Hgpsmentioning

confidence: 99%

Laminopathies and Atherosclerosis

Alshali

Hegele

2004

ATVB

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“…The mature DA vessel wall structure is highly similar to the premature ageing histopathology seen in vessels of children with the Hutchinson-Gilford syndrome (HGPS) [6]. This syndrome is based on a genetic defect in the lamin A (LMNA) gene which leads to pathological accumulation of the splice variant progerin [7,8]. Increased progerin expression has also been reported during normal vascular ageing [9,10].…”

Section: Introductionmentioning

confidence: 78%

“…In our study, we introduced for the first time a role for lamina A/C and progerin [11]. This observation was triggered by the histopathology found in the vessel wall of young adolescents with the HGPS [8], in which premature atherosclerosis was observed. The physiological development of prenatal intimal thickening and the development of cytolytic necrosis in the DA showing contractions after birth mimic the degenerative changes seen in the HGPS.…”

Section: Discussionmentioning

confidence: 97%

Progerin Expression during Normal Closure of the Human Ductus Arteriosus: A Case of Premature Ageing?

Groot

Bökenkamp

Raz

et al. 2016

Etiology and Morphogenesis of Congenital Heart Disease

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The ductus arteriosus (DA) is a fetal vessel bypassing the still nonfunctional lungs. Closure of the DA at birth is essential for the transition from a fetal to a neonatal circulation. This closing process begins with a physiological contraction followed by definitive anatomical closure. The latter process starts already before birth by development of intimal thickening followed after birth by degeneration of the inner media, including cytolytic necrosis and apoptosis. The DA will remain patent when there is insufficient maturation in prematurely born babies or when there is a structural abnormality as seen in persistent DA (PDA). The histological changes during normal DA closure resemble the features seen in the premature ageing vessels in children with the Hutchinson progeria syndrome. The latter syndrome is caused by a mutation in the lamin A/C gene resulting in accumulation of the progerin splice variant. We studied human DA biopsies from the fetal to the neonatal period to investigate whether lamin A/C and progerin might be involved in the DA closure process. The results

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“…The arteries of HGPS patients, however, show particularly severe depletion of smooth muscle cells and derangement of basement membrane [21]. It might therefore be best described as an arterial smooth muscle dystrophy.…”

Section: Introductionmentioning

confidence: 99%

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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Histological and Ultrastructural Features of Atherosclerosis in Progeria

Cited by 126 publications

References 35 publications

Laminopathies and Atherosclerosis

Laminopathies and Atherosclerosis

Progerin Expression during Normal Closure of the Human Ductus Arteriosus: A Case of Premature Ageing?

Collagen expression in fibroblasts with a novel LMNA mutation

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