Aortic Connective Tissue in Ageing—A Biochemical Study

Andreotti, L; Bussotti, Alessandro; Cammelli, Daniele; Giovine, F; Sampognaro, Salvatore; Sterrantino, Gaetana; Varcasia, Giuseppe; Arcangeli, P

doi:10.1177/000331978503601206

Cited by 47 publications

(33 citation statements)

References 29 publications

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“…In this study, we found that prolyl 4-hydroxylase aI and aII subunit were down-regulated in senescent HUVECs. This suggests that down-regulation of prolyl 4-hydroxylase may contribute to the decrease of collagen observed in aorta during senescence (Andreotti et al, 1985).…”

Section: Discussionmentioning

confidence: 89%

Searching for Genes Involved in Arteriosclerosis: Proteomic Analysis of Cultured Human Umbilical Vein Endothelial Cells Undergoing Replicative Senescence

Kamino

Hiratsuka

Toda

et al. 2003

Cell Struct. Funct.

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ABSTRACT. It is known that replicative senescence of endothelium in vivo contributes at least partially to agerelated vascular disorders such as arteriosclerosis. However, the genes involved in this process remain to be identified. In this study, we employed a proteomics-based approach to identify candidate genes using in vitro cultured human umbilical vein endothelial cells (HUVECs) as an experimental model for replicative senescence. By comparing protein spots from young and senescent HUVECs using two-dimensional electrophoresis, we identified three up-regulated proteins and five down-regulated proteins in senescent HUVECs as compared to young HUVECs, whose alteration was not observed during replicative senescence of primary human fibroblasts. Consistent results were obtained in Western blotting analysis using specific antibodies raised against some of these proteins, whereas there were no significant changes in the mRNA levels of these genes during senescence of HUVECs. Among them, cathepsin B, a protease participating in both intracellular proteolysis and extracellular matrix remodeling was observed to be dramatically up-regulated in senescent HUVECs and whose activity is known to be up-regulated in atherosclerotic lesions with senescence-associated phenotypes in vivo. Additional proteins, including cytoskeletal proteins and proteins involved in the processes of synthesis, turnover and modification of protein, were identified, whose function in endothelium was previously unsuspected. These proteins identified by a proteomics-based approach using cultured HUVECs may be involved not only in replicative senescence but also in functional alterations in vascular endothelial cells with senescence-associated phenotypes and may serve as molecular markers for these processes.

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Section: Discussionmentioning

confidence: 89%

Searching for Genes Involved in Arteriosclerosis: Proteomic Analysis of Cultured Human Umbilical Vein Endothelial Cells Undergoing Replicative Senescence

Kamino

Hiratsuka

Toda

et al. 2003

Cell Struct. Funct.

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“…Samples were then processed for ultrastructural examination, and the remaining tissue was frozen in liquid nitrogen and stored at -80°C for lysyl oxidase activity assay. (8) 166±28 (8) 120±15 (6) Age 60 199±7.5 (13) l,780±225 (8) 283±28 (8) 141 ±14 (5) (days) 240 559±69 (8) l,940±281 (8) 350±50 (8) 2O0±16 (5) …”

Section: Morphologymentioning

confidence: 99%

“…(8) l,860±149 (8) 340±79 (8) 175±26 (5) Values are reported as mean±SD and (number of animals analyzed).…”

Section: ±60mentioning

confidence: 99%

Role of the extracellular matrix in age-related modifications of the rat aorta. Ultrastructural, morphometric, and enzymatic evaluations.

Fornieri

Quaglino

Mori

1992

Arterioscler Thromb

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Connective tissues such as blood vessels are known to be greatly affected by age because of impaired functional properties and increased susceptibility to diseases. With the aim of providing further information on the role of the extracellular matrix in age-related modifications, we investigated the aorta in the rat model from birth to senescence by means of morphological and morphometric observations and by evaluation of lysyl oxidase activity. Results focused on the dramatic vascular rearrangements due to progressive fibrosis of the extracellular matrix and on prominent elastin modifications. The presence of lysyl oxidase activity, even in the oldest animals, might be at least partly responsible for the increased stiffness of the aging extracellular matrix. The striking age-related remodeling of the aortic architecture and the alterations of the interactions between cellular and extracellular compartments might greatly influence the functional properties of the arterial wall in senescence, at least contributing to the consequences of some apparently age-related vascular disorders. ( integrated system composed of collagen fibrils, elastic lamellae, proteoglycans, minor collagens, and structural glycoproteins that, together with cells, guarantees the major properties of the vascular compartment, i.e., the diffusion at proper rates of nutrients and other metabolic factors through optimal blood flow. -4Apart from calcifications, fibrosis, and atheromatous lesions, which are frequently observed in the vessel wall of several species 5 " 9 and which are at least partly responsible for the failure of the cardiovascular system with age, 7 little is known about the pathogenesis of the age-related modifications of the vessel wall, which may affect vascular properties such as elasticity and resilience and which may be of paramount importance in understanding specific pathological conditions. The present work was undertaken with the aim of focusing attention on the age-related modifications of the aortic arch in rats from birth to senescence. Qualitative and quantitative morphological data concerning the structure and distribution of the cellular and extracellular components were correlated with the activity of lysyl oxidase, the enzyme that catalyzes the formation of collagen and elastin cross-links and therefore contributes to the stabilization of these two polymers. Supported by Fondi (40%) and Ministero Universita e Ricerca Scientifica e Technologica (60%).Address for correspondence: Prof. C. Fornieri, 1st. Patologia Generale, Via Campi 287, 41100 Modena, Italy.Received April 21, 1992; accepted May 13, 1992. In the light of our results, we suggest that the interactions of the cellular and the extracellular compartments and the ratio between collagen and elastin play key roles in conditioning the morphological-functional properties of the arterial wall and, therefore, explain at least some of the consequences (although not the pathogenesis) of several pathological processes affecting the vascular compartment with inc...

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“…To our knowledge, this is the first study of these elastin regulatory mechanisms in an SIOD aorta and in developing unaffected human aortae. Prior studies of elastin protein concentration (21,22) and ELN mRNA levels (33) in the human aorta found that both decrease postnatally with age. To define this developmental decline in elastin better, we characterized aortic ELN mRNA expression during fetal development and postnatally.…”

Section: Discussionmentioning

confidence: 96%

“…Similarly, within the human aorta, insoluble elastin protein concentration increases during fetal development (20) and then progressively declines (21,22).…”

mentioning

confidence: 98%

Transcriptional and posttranscriptional mechanisms contribute to the dysregulation of elastogenesis in Schimke immuno-osseous dysplasia

Morimoto

Wang

et al. 2015

Pediatr Res

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BACKGROUND: Schimke immuno-osseous dysplasia (SIOD)is an autosomal recessive disorder caused by mutations in SMARCAL1. A frequent complication is arteriosclerosis associated with reduced elastin expression; however, the mechanism underlying the reduced elastin expression remains unknown. METHODS: Expression of transcriptional regulators of elastin (ELN) and microRNA (miRNA) regulators of ELN messenger RNA (mRNA), ELN promoter methylation, and ELN mRNA poly(A) tail length were assessed by quantitative RT-PCR, bisulfite Sanger sequencing, and the Poly(A) Tail Length Assay Kit, respectively, in unaffected developing human aortae and in an SIOD aorta. RESULTS: Comparing unaffected fetal and adult aortae, ELN precursor mRNA (pre-mRNA) levels remained nearly constant, whereas mRNA levels declined by ~10 2 -fold. This corresponded with a reduction in poly(A) tail length but not with changes in the other parameters. In contrast, compared to the unaffected fetal aortae, the SIOD aorta had 18-fold less ELN pre-mRNA and 10 4 -fold less mRNA. This corresponded with increased expression of miRNA regulators and shorter ELN mRNA poly(A) tail lengths but not with altered expression of ELN transcriptional regulators or ELN promoter methylation. CONCLUSION: Posttranscriptional mechanisms account for the reduction in ELN mRNA levels in unaffected aortae, whereas transcriptional and posttranscriptional mechanisms reduce elastin expression in SIOD aorta and predispose to arteriosclerosis.S chimke immuno-osseous dysplasia (SIOD, OMIM 242900) is a rare autosomal recessive multisystemic disorder caused by mutations in the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1) gene (1). SMARCAL1 functions as a DNA-dependent annealing helicase (2) that recognizes single-stranded to double-stranded DNA transitions and binds to transcriptionally active chromatin (3). SMARCAL1 is involved in the DNA stress response (4,5), the reactivation of stalled replication forks (6)(7)(8), and the modulation of gene expression (3). Key manifestations of the disease include growth failure due to spondyloepiphyseal dysplasia, renal failure due to focal segmental glomerulosclerosis, T-cell immunodeficiency, facial dysmorphism, and hyperpigmented macules (9). Approximately 50% of SIOD patients also develop vascular disease (10), and the vascular complications are refractory to treatment and a common cause of death (11).The vascular disease in SIOD manifests as migraine-like headaches, transient ischemic attacks, and cerebrovascular accidents (11). The arterial histopathology shows intimal and medial hyperplasia, smooth muscle cell hyperplasia, and fragmented and disorganized elastin fibers (10,12). Molecular studies suggest reduced elastogenesis (10); however, the mechanism underlying this remains unknown.Elastin, which is critical for the development and maintenance of the arteries (13,14), confers the elastic recoil properties required for the proper function of the arteries as well as other load-bearing...

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Aortic Connective Tissue in Ageing—A Biochemical Study

Cited by 47 publications

References 29 publications

Searching for Genes Involved in Arteriosclerosis: Proteomic Analysis of Cultured Human Umbilical Vein Endothelial Cells Undergoing Replicative Senescence

Searching for Genes Involved in Arteriosclerosis: Proteomic Analysis of Cultured Human Umbilical Vein Endothelial Cells Undergoing Replicative Senescence

Role of the extracellular matrix in age-related modifications of the rat aorta. Ultrastructural, morphometric, and enzymatic evaluations.

Transcriptional and posttranscriptional mechanisms contribute to the dysregulation of elastogenesis in Schimke immuno-osseous dysplasia

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