Can proteomics yield insight into aging aorta?

Fu, Zhang; Wang, Mingyi; Lakatta, Edward G.; Eyk, Jennifer E. Van

doi:10.1002/prca.201200138

Cited by 8 publications

(5 citation statements)

References 155 publications

(289 reference statements)

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“…Proteomic studies for human chronological aging of aortic media have been rarely carried out. However, a rat aortic proteomics study focusing on chronological aging was carried out by Fu et al 18,19 The authors showed that the expression of MFGE8 was increased with aging, suggesting that MFGE8 was involved in the signaling of age-associated thickening in rats' aorta. In the present study, the expression of MFGE8 was also increased with human aortic aging (fold change; 7.11 vs young group, 2.44 vs middleaged group; Table S5).…”

Section: Discussionmentioning

confidence: 99%

Age‐associated proteomic alterations in human aortic media

Miura

Tsumoto

Iwamoto

et al. 2019

Geriatrics Gerontology Int

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Aim Human vascular senescence, which mainly occurs in media, is not completely understood. Here, we used proteomic approaches to investigate age‐associated changes in human aortic media with the goal of understanding the molecular mechanisms underlying vascular senescence. Method Cryopreserved autopsy samples of aortic media from older‐aged (aged 70–100 years, n = 25), middle‐aged (aged 49–68 years, n = 24), and young (aged 21–39 years, n = 12) subjects were collected. We used two proteomic techniques, two‐dimensional differential gel electrophoresis and isobaric tags for relative and absolute quantitation, and we subjected differentially‐expressed proteins among age groups to immunohistochemical analyses. Results Proteomic analyses showed that the expression of lactadherin, which produces medin, was elevated in aortic media of older‐aged individuals. Immunohistochemical and Congo red staining showed that lactadherin and apolipoprotein E were deposited, and that amyloidosis was enhanced in older‐aged aortic media. Furthermore, the markers of oxidative damage (8‐hydroxy‐2'‐deoxyguanosine and 4‐hydroxy‐2‐nonenal) were significantly elevated in aortic media of middle‐aged or older‐aged individuals. The immunohistochemical expression of anti‐oxidant proteins (thioredoxin and extracellular superoxide dismutase) was also high in middle‐aged and older‐aged groups. Oxidative damage might induce the disruption of smooth muscle cells, resulting in the decrement of α‐actin, a highly‐expressed protein in smooth muscle cells, and matrix remodeling, in which several proteins associated with extracellular matrix were altered with aging. Conclusions Proteomic approaches showed that the elevated expression of lactadherin might contribute to amyloid deposition, enhancement of oxidative stress, induction of antioxidant proteins and matrix remodeling in older‐aged aortic media. Geriatr Gerontol Int 2019; 19: 1054–1062.

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Section: Discussionmentioning

confidence: 99%

Age‐associated proteomic alterations in human aortic media

Miura

Tsumoto

Iwamoto

et al. 2019

Geriatrics Gerontology Int

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“…It is known that this protein is a transcriptional regulator of the poloid kinase Plk1 in smooth muscle 34 . A recent study has observed an increase in the expression of this protein in aortas of elderly individuals, suggesting that it promotes the instability of microtubules and actin filaments 35 .…”

Section: Discussionmentioning

confidence: 96%

Efecto de dosis suprafisiológicas de calcitriol sobre la expresión proteica de células de músculo liso vascular

López

LePoultel

Quirós

et al. 2017

Rev Osteoporos Metab Miner

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Introduction: Calcitriol, essential for maintaining calcium and phosphorus homeostasis in the body, may damage the vascular system in high doses, increasing the risk of calcification. Objective: To assess the differential expression of proteins in vascular smooth muscle cells subjected to a supra-physiological dose of calcitriol. Material and methods: Rat vascular smooth muscle cells (VSMC-R) were cultured in the presence of 10 -7 M calcitriol for 10 days. The change of muscle to bone phenotype was assessed by alkaline phosphatase activity, immunocytochemistry, quantitative polymerase chain reaction in time (QPCR) and Western blot analysis. By means of two-dimensional electrophoresis and mass spectrometry was evaluated for the differential protein pattern in presence and absence of 10 -7 M calcitriol. Results: Exposure to a high dose of calcitriol decreased elastin gene expression and the protein and gene expression of α-actin protein, increased gene expression of osteocalcin and Runx2 and expression of osteoprotegerin protein. At the proteomic level, 10 differentially expressed proteins were identified, highlighting the increase in mitochondrial superoxide dismutase, cytoskeleton proteins, vesicle formation and inflammasome. On the contrary, there were 4 proteins that diminished expression, highlighting some of muscular type. Conclusions: In a model of vascular smooth muscle cells submitted to a supra-physiological dose of calcitriol an increased expression of cytoskeleton proteins was observed. These proteins form matrix vesicles and participate in clearance of free radicals and in the inflammatory response. The loss of muscle phenotype was represented by decreased expression of typically muscle proteins.

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“…MFG-E8 induces cell death and angiogenesis in aorta, and is considered associated with aging-related vascular diseases. 29,30 Since older age is a risk factor for AAA, and adventitial angiogenesis is a known pathobiological change in AAA, MFG-E8 possibly plays regulatory roles in AAA pathogenesis pathways.…”

Section: Discussionmentioning

confidence: 99%

Discovery of crucial cytokines associated with abdominal aortic aneurysm formation by protein array analysis

Yang

Sun

et al. 2019

Exp Biol Med (Maywood)

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As a common disease, abdominal aortic aneurysm (AAA) features permanently progressively dilated abdominal aorta. Various cytokines are implicated in AAA pathogenesis. Clarification of involved cytokines combined with functional analysis may provide new insights into AAA pathogenesis. Using a mouse model, this study analyzed the cytokine profiles in AAA. Cytokines were measured in AAA tissues of saline control or angiotensin II-treated ApoE−/− mice using an antibody array of 200 cytokines, cytokine receptors, and related proteins. Statistical analysis revealed that 21 of 200 proteins were differentially expressed in AAA. These differentially expressed proteins were subjected to function and pathway enrichment analysis, which revealed that leukocyte migration and positive regulation of cell adhesion were the most significant biological processes. Specific signaling pathways, including Janus kinase/signal transducers and activators of transcription and cytokine–cytokine receptor interaction, were prominent in Kyoto encyclopedia of genes and genomes pathway enrichment analysis. Importantly, our data identified cytokines which had not previously been illustrated in AAA pathogenic pathways. Bivariate correlation analysis between these cytokines and protease activity showed that granulocyte colony-stimulating factor (G-CSF), macrophage inflammatory protein 1 g, cardiotrophin 1, milk fat globule-EGF factor 8 protein, interleukin 33, and periostin were positively correlated with matrix metalloprotease 1 (MMP-1), MMP-9, cathepsin B, and cathepsin L. G-CSF was positively correlated with cathepsin L. In conclusion, these results demonstrate that cytokine profile is significantly altered in AAA, and that the newly identified crucial cytokines may function potentially in AAA pathogenesis. Impact statement Various cytokines are known contributors to abdominal aortic aneurysm (AAA) pathologic processes, but the mechanisms underlying the pathogenesis remains unclear. We illustrated the altered cytokine profiles in AAA by high throughput antibody array of 200 cytokines, cytokine receptors and related proteins, as well as bioinformatics analysis of differentially expressed proteins in lesion tissues from AAA mice infused with angiotensin II. Functional analyses of differentially expressed cytokines showed clustering on cell migration and adhesion processes. More importantly, crucial cytokines whose association with AAA formation had not been established were identified. Significant correlations were found between these cytokines and protease activity. This study identifies several crucial markers for further researches on the molecular basis of AAA.

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Can proteomics yield insight into aging aorta?

Cited by 8 publications

References 155 publications

Age‐associated proteomic alterations in human aortic media

Age‐associated proteomic alterations in human aortic media

Efecto de dosis suprafisiológicas de calcitriol sobre la expresión proteica de células de músculo liso vascular

Discovery of crucial cytokines associated with abdominal aortic aneurysm formation by protein array analysis

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