Systems biology—opportunities and challenges: the application of proteomics to study the cardiovascular extracellular matrix

Barallobre-Barreiro, Javier; Lynch, Magnus; Yin, Xiaoke; Mayr, Manuel

doi:10.1093/cvr/cvw206

Cited by 32 publications

(23 citation statements)

References 123 publications

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“…Likewise, but opposite, a group of typical coagulation-and thrombocyte-related proteins (identities can be seen in Table IV in the online-only Data Supplement) displayed much lower concentrations (ratios 0.35-0.65) in the wall material than in the thrombus (Figure 2; Table IV in the online-only Data Supplement). In the wall samples, 88, 59, and 33 of the identified proteins could be categorized as classical plasma proteins, 19 cytoskeletal proteins, 20 and ECM proteins, 21 respectively as shown in Table 2. Likewise, among the thrombus samples 77, 37, and 24 were categorized as plasma proteins, ECM, and cytoskeletal proteins, respectively.…”

Section: Resultsmentioning

confidence: 99%

Abdominal Aortic Aneurysms Growth Is Associated With High Concentrations of Plasma Proteins in the Intraluminal Thrombus and Diseased Arterial Tissue

Andersen

Lindholt

Urbonavičius

et al. 2018

ATVB

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Objective-Porosity of the intraluminal thrombus (ILT) is believed to convey biologically active components from the bloodstream toward the aneurismal wall. Accumulation of molecules in the abdominal aortic aneurysmatic tissue may influence vascular protein turnover and regulate abdominal aortic aneurysm growth. We sought to identify proteins with concentrations in the ILT and the abdominal aortic aneurysm wall which associate with aneurysmal expansion rate. Approach and Results-Proteomic analysis by liquid chromatography tandem-mass spectrometry of separated wall and ILT samples was correlated with preoperative aneurysmal growth rate in 24 individuals operated electively for infrarenal abdominal aortic aneurysm. The median preoperative growth rate was 3.8 mm/y (interquartile range, 3) and the mean observational time was 3.3±1.7 years. Plasma components dominated the group of proteins with tissue concentrations, which correlate positively with growth rates (P<0.001, Fisher exact test, both in the ILT and the wall). In contrast, in the wall and thrombus samples, ECM (extracellular matrix) proteins were significantly more prevalent in the group of proteins with negative correlations to growth rates (P<0.05, Fisher exact test). Similarly, a long series of proteins, related to cellular functions correlated negatively to growth rates. Conclusions-When the preoperative aneurysmatic growth rate has been high, the concentration of many plasma proteins residing in the ILT and the aneurysmatic tissue is also high, compatible with the hypothesis of increased tissue porosity and accumulation of plasma components as a driver of aneurysm expansion. Moreover, many matrix and cellular proteins which are found in high concentrations in slower-growing aneurysms provides new knowledge about potential treatment targets. Visual Overview-An online visual overview is available for this article.

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Section: Resultsmentioning

confidence: 99%

Abdominal Aortic Aneurysms Growth Is Associated With High Concentrations of Plasma Proteins in the Intraluminal Thrombus and Diseased Arterial Tissue

Andersen

Lindholt

Urbonavičius

et al. 2018

ATVB

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“…buffers containing surfactants such as sodium dodecyl sulphate, SDS) are often less effective at extracting ECM. We therefore trialled two alternative conditions to extract ECM proteins from mouse skin (Barallobre-Barreiro, et al 2016). While ionic disruption using high salt extracted more unique ECM proteins in total, we used chaotropic disruption with urea as this yielded elastic fibre proteins (fibrillin and fibulin) that were absent from the high salt extraction method.…”

Section: Discussionmentioning

confidence: 99%

Distinct matrix composition and mechanics in aged and estrogen-deficient mouse skin

Saville¹,

Mallikarjun²,

Holmes³

et al. 2019

Preprint

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Hormone deficiency has been widely linked to accelerated tissue ageing, and increased incidence of chronic degenerative disease. Furthermore, age-associated hormonal dysregulation is thought to be a major contributing factor to the increased fragility of aged skin. The ageing process is driven by an aggregation of damage to cells and extracellular matrix, which can directly influence the mechanical properties of the tissue. Here we report on the correlation between mechanical properties and composition of skin from ovariectomised and aged mice, to assess the extent to which estrogen deprivation drives dermal ageing. We found that age and estrogen abrogation affected skin mechanical properties in contrasting ways: ageing led to increased tensile strength and stiffness while estrogen deprivation had the opposite effect. Mass spectrometry proteomics showed that the quantity of extractable fibrillar collagen-I decreased with ageing, but no change was observed in ovariectomised mice. This observation, in combination with measurements of tensile strength, was interpreted to reflect changes to the extent of extracellular matrix crosslinking, supported by a significant increase in the staining of advanced glycation endpoints in aged skin. Loss of mechanical strength in the skin following ovariectomy was consistent with a loss of elastic fibres. Other changes in extracellular matrix composition broadly correlated between aged and ovariectomised mice, confirming the important role of estrogen-related pathways in ageing. This study offers new insight into the relationship between tissue composition and mechanics, and suggests that the deleterious effects of intrinsic skin ageing are compounded by factors beyond hormonal dysregulation.

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Section: Discussionmentioning

confidence: 99%

“…Our 3-step extraction method for ECM proteins ("English Quickstep") 6 has allowed characterizing the ECM in a variety of cardiovascular tissues. Fractionation of the tissue into several extracts is required to obtain a simplified ECM proteome as discussed elsewhere 6 . Intracellular proteins would otherwise contribute to an excessive dynamic range of protein abundances within the extracts that would hinder identification of less abundant ECM proteins.…”

Section: Discussionmentioning

confidence: 99%

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Glycoproteomics of the Extracellular Matrix: A Method for Intact Glycopeptide Analysis Using Mass Spectrometry

Barallobre-Barreiro

Baig

Fava

et al. 2017

JoVE

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Fibrosis is a hallmark of many cardiovascular diseases and is associated with the exacerbated secretion and deposition of the extracellular matrix (ECM). Using proteomics, we have previously identified more than 150 ECM and ECM-associated proteins in cardiovascular tissues. Notably, many ECM proteins are glycosylated. This post-translational modification affects protein folding, solubility, binding, and degradation. We have developed a sequential extraction and enrichment method for ECM proteins that is compatible with the subsequent liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of intact glycopeptides. The strategy is based on sequential incubations with NaCl, SDS for tissue decellularization, and guanidine hydrochloride for the solubilization of ECM proteins. Recent advances in LC-MS/MS include fragmentation methods, such as combinations of higher-energy collision dissociation (HCD) and electron transfer dissociation (ETD), which allow for the direct compositional analysis of glycopeptides of ECM proteins. In the present paper, we describe a method to prepare the ECM from tissue samples. The method not only allows for protein profiling but also the assessment and characterization of glycosylation by MS analysis.

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Systems biology—opportunities and challenges: the application of proteomics to study the cardiovascular extracellular matrix

Cited by 32 publications

References 123 publications

Abdominal Aortic Aneurysms Growth Is Associated With High Concentrations of Plasma Proteins in the Intraluminal Thrombus and Diseased Arterial Tissue

Abdominal Aortic Aneurysms Growth Is Associated With High Concentrations of Plasma Proteins in the Intraluminal Thrombus and Diseased Arterial Tissue

Distinct matrix composition and mechanics in aged and estrogen-deficient mouse skin

Glycoproteomics of the Extracellular Matrix: A Method for Intact Glycopeptide Analysis Using Mass Spectrometry

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