Proteomics Analysis of Cardiac Extracellular Matrix Remodeling in a Porcine Model of Ischemia/Reperfusion Injury

Barallobre-Barreiro, Javier; Didangelos, Athanasios; Schoendube, Friedrich A.; Drozdov, Ignat; Yin, Xiaoke; Fernandez-Caggiano, Mariana; Willeit, Peter; Püntmann, Valentina O.; Aldama-López, Guillermo; Shah, Ajay M.; Doménech, Nieves; Mayr, Manuel

doi:10.1161/circulationaha.111.056952

Cited by 200 publications

(171 citation statements)

References 40 publications

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“…17 Asporin was also like fibromodulin downregulated in patients with high PWV, and both proteoglycans contribute to cardiac remodeling in an animal model of reperfusion. 18 In general, the SLRPs are working cooperatively and synergistic in the regulation of collagen fibrillogenesis and have the ability of altering expression in the absence of other members of the proteoglycan family. 19 Interestingly, a mouse model with knockout of biglycan presented with aortic dissection and rupture.…”

Section: Discussionmentioning

confidence: 99%

“…18 In general, the SLRPs are working cooperatively and synergistic in the regulation of collagen fibrillogenesis and have the ability of altering expression in the absence of other members of the proteoglycan family. 19 Interestingly, a mouse model with knockout of biglycan presented with aortic dissection and rupture.…”

Section: Hansen Et Al Proteomics On Human Arterial Tissue and Pwv 1901mentioning

confidence: 99%

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Proteome Analysis of Human Arterial Tissue Discloses Associations Between the Vascular Content of Small Leucine-Rich Repeat Proteoglycans and Pulse Wave Velocity

Hansen

Beck

Irmukhamedov

et al. 2015

ATVB

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Objectives-We hypothesized that arterial stiffness is associated with changes in the arterial protein profile, particularly of extracellular matrix components. We aimed at determining differentially expressed proteins by quantitative proteome analysis in arterial tissue from patients with different degrees of arterial stiffness. Approach and Results-Arterial stiffness, assessed by carotid-femoral pulse wave velocity (PWV), central blood pressure and augmentation index by pulse wave analysis were measured the day before surgery in a group of patients undergoing coronary artery bypass grafting. Protein extracts of well-defined, homogenous, nonatherosclerotic individual samples of the left mammary artery from 10 of these patients with high PWV and 9 with low PWV were compared by quantitative proteome analysis, using tandem mass tag labeling and nano-liquid chromatography mass spectrometry/mass spectrometry. Of 418 quantified proteins, 28 were differentially expressed between the groups with high and low PWV (P<0.05). Three of 7 members of the extracellular matrix family of small leucine-rich repeat proteoglycans displayed significant differences between the 2 groups (P=0.0079; Fisher exact test). Three other ECM proteins were differentially regulated, that is, collagen, type VIII, α-1 and α-2 and collagen, type IV, α-1. Several proteins related to smooth muscle cell function and structure were also found in different amounts between the 2 groups. Conclusions-Changes in the arterial amounts of small leucine-rich proteoglycans, known to be involved in collagen fibrillogenesis, and of some nonfibrillar collagens in combination with alterations in proteins related to functions of the human arterial smooth muscle are associated with arterial stiffness, as determined by PWV. fibril organization and fibrillogenesis. 8 Mice knockout models for SLRPs display disorganized collagen fibril network and loses functions of the connective tissue and present with different disorders related to abnormal collagen fibril sizes and network, such as aortic dissection and rupture, skin fragility, joint laxity, and tendon weakness. 9,10 In this study, we hypothesized that patients with a high degree of arterial stiffness display a specific protein expression pattern different from patients with a normal low degree of arterial stiffness. We applied a quantitative proteomic approach to identify differentially expressed proteins in individual arterial tissue samples obtained from patients with high and low PWV. We investigate the internal mammary artery because this vessel has proven to be a suitable model artery for studies of generalized nonatherosclerotic arterial changes, that is, its matrix composition, endothelial function, and biochemistry reflect alterations in both the coronary and carotid arteries, as well as other features related to the arterial system. 11-13 MethodsMaterials and Methods are available in the online-only Data Supplement. ResultsBaseline patient characteristics are summarized in Table 1. There were no statistical d...

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Section: Discussionmentioning

confidence: 99%

Section: Hansen Et Al Proteomics On Human Arterial Tissue and Pwv 1901mentioning

confidence: 99%

Proteome Analysis of Human Arterial Tissue Discloses Associations Between the Vascular Content of Small Leucine-Rich Repeat Proteoglycans and Pulse Wave Velocity

Hansen

Beck

Irmukhamedov

et al. 2015

ATVB

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“…cardiovascular extracellular matrix. 56,57 By using a decellularization step, we overcome differences in cellular heterogeneity. Tissue heterogeneity is a major concern for any omics technology.…”

Section: Proteomics: Assessing Vascular Integrity By Monitoring Protementioning

confidence: 99%

MicroRNAs Within the Continuum of Postgenomics Biomarker Discovery

Mayr

Zampetaki

Willeit

et al. 2013

ATVB

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Discovery of novel biomarkers and improvement of risk prediction algorithms will be a key to fulfill the promise of personalized medicine. Although genuine personalized treatment is probably an unrealistic expectation within the budget constraints of current health systems, a stratified medicine approach to identify individuals at high risk may help to allocate available resources most efficiently in a setting with a rising epidemic of cardiovascular disease (CVD) fueled by obesity, hypertension, and diabetes mellitus and by an aging population. Besides, biomarkers may improve patient motivation; by facilitating risk communication and compliance to lifestyle changes and therapies.The search for cardiovascular biomarkers dates back to the mid 1960s when creatine kinase and its cardiospecific isoform creatine kinase-MB were established as indicators of acute myocardial damage.1 About a decade later, the Framingham Study pioneered the quest for long-term cardiovascular risk prediction. Framingham risk scores, 2 as well as others, such as Prospective Cardiovascular Münster (PROCAM) study, Systemic Coronary Risk Evaluation (SCORE), and Reynolds, 3 are widely accepted and implemented tools in clinical decision-making. These scores inform treatment decisions, but they leave ample room for improvement. Currently, the majority of cardiovascular risk is not explained by traditional risk factors. In fact, most events occur in patients with an average risk score who are erroneously deemed to be at intermediate or low risk because they have no or only 1 of the cardiovascular risk factors. 4 In contrast, many high-risk individuals do not experience a cardiovascular event even in the long term.5 Thus, the renewed interest in biomarkers is warranted, and the recent advances in postgenomic technologies offer unprecedented opportunities for biomarker discovery. How Well Do Current Cardiovascular Risk Factors Predict Risk?Up to now, biomarkers linked to systemic and vascular inflammation, oxidative stress, or vascular calcification received most of the attention. In the latest (2010) Abstract-The postgenomic shift in paradigm from reductionism to systems-wide network inference has increased recognition that cardiovascular diseases are not simply determined by the genome but arise from an interaction and dynamic dysregulation of gene regulatory networks, proteins, and metabolic alterations. The advent of postgenomic technologies promises to interrogate these complex pathophysiological perturbations by applying concepts of systemic relationships to biomarker discovery. A multibiomarker panel consisting of biomarkers capturing different levels of information (eg, microRNAs to assess endothelial and platelet activation, molecular lipid species to profile metabolic status, and proteolytic degradation products to assess vascular integrity) could outperform inflammatory biomarkers without vascular specificity in their ability of predicting cardiovascular risk. As atherosclerosis develops over decades, different biomarkers may be requir...

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“…21,22 Typically, a lane is subdivided into equal rectangles from top to bottom, and digested by trypsin similar to that done for 2-DE gel spots. However, precious information that could be gained from such processing, like the approximate molecular weight, is rarely incorporated in proteome analyses and content management (see section titled Software Analysis).…”

Section: Liquid Chromatographymentioning

confidence: 99%

“…SDS-PAGE is particularly useful if a sample is not directly compatible with LC-MS, eg, because of high salt concentration. 22 The reviewed examples demonstrate that 2-DE and LC both support the analysis of thousands of proteins. However, LC-based proteomics approaches are mostly based on prior digestion of the sample into peptides.…”

Section: Liquid Chromatographymentioning

confidence: 99%

High-Resolution Separation of Cardiovascular Proteomes

Drews

2012

Circ Cardiovasc Genet

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Proteomics Analysis of Cardiac Extracellular Matrix Remodeling in a Porcine Model of Ischemia/Reperfusion Injury

Abstract: Our findings reveal a biosignature of early- and late-stage ECM remodeling after myocardial ischemia/reperfusion injury, which may have clinical utility as a prognostic marker and modifiable target for drug discovery.

Cited by 200 publications

References 40 publications

Proteome Analysis of Human Arterial Tissue Discloses Associations Between the Vascular Content of Small Leucine-Rich Repeat Proteoglycans and Pulse Wave Velocity

Proteome Analysis of Human Arterial Tissue Discloses Associations Between the Vascular Content of Small Leucine-Rich Repeat Proteoglycans and Pulse Wave Velocity

MicroRNAs Within the Continuum of Postgenomics Biomarker Discovery

High-Resolution Separation of Cardiovascular Proteomes

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