Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Proteomics approaches to the systems biology of cardiovascular diseases

Drake, Thomas A.; Ping, Peipei

doi:10.1194/jlr.r600027-jlr200

Cited by 30 publications

(19 citation statements)

References 71 publications

(69 reference statements)

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“…In order to understand how complex biological systems such as cells, tissues, or organs are altered in disease, it is imperative to not only identify the constituents of the system but also to know how those constituents interact with each other to bring about functional outcomes (15, 41). Consequently, MS-based identification of proteins and protein interacting partners is an essential first step on the path to understanding complex clinical syndromes such as HF.…”

Section: Protein Identificationmentioning

confidence: 99%

“…A systems level understanding of biological processes and the signaling pathways that regulate them, necessitates the ability to assess how the elements of the system change over a range of perturbations (15). Thus, the quantification of protein expression and PTM occupancy changes is of the upmost importance for understanding complex syndromes such as HF at the systems level.…”

Section: Protein Quantificationmentioning

confidence: 99%

“…Thus, proteomics, which is concerned with the comprehensive characterization of all facets of protein biology, including the determination of protein localization, modifications, interactions, activities, and, ultimately, their function (17), is particularly well-suited for advancing our understanding of complex disease mechanisms at the systems level (15). Unfortunately, unlike the genome, which is considered to be largely static, the proteome is highly dynamic owing to a large dynamic range of protein expression as well as considerable complexity that can be attributed to a myriad protein forms, or “proteoforms” (48), arising from mutations, truncations, alternative splicing events, and the addition of post-translational modifications (PTMs), which makes analysis of the proteome technically challenging.…”

Section: Introductionmentioning

confidence: 99%

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Proteomics in heart failure: top-down or bottom-up?

Gregorich

Chang

2014

Pflugers Arch - Eur J Physiol

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Summary The pathophysiology of heart failure (HF) is diverse, owing to multiple etiologies and aberrations in a number of cellular processes. Therefore, it is essential to understand how defects in the molecular pathways that mediate cellular responses to internal and external stressors function as a system to drive the HF phenotype. Mass spectrometry (MS)-based proteomics strategies have great potential for advancing our understanding of disease mechanisms at the systems level because proteins are the effector molecules for all cell functions and, thus, are directly responsible for determining cell phenotype. Two MS-based proteomics strategies exist: peptide-based bottom-up and protein-based top-down proteomics—each with its own unique strengths and weaknesses for interrogating the proteome. In this review, we will discuss the advantages and disadvantages of bottom-up and top-down MS for protein identification, quantification, and the analysis of post-translational modifications, as well as highlight how both of these strategies have contributed to our understanding of the molecular and cellular mechanisms underlying HF. Additionally, the challenges associated with both proteomics approaches will be discussed and insights will be offered regarding the future of MS-based proteomics in HF research.

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Section: Protein Identificationmentioning

confidence: 99%

Section: Protein Quantificationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Proteomics in heart failure: top-down or bottom-up?

Gregorich

Chang

2014

Pflugers Arch - Eur J Physiol

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“…The field of systems biology aims to obtain a holistic, global, and integrated understanding of the molecular constituents of biological systems, including nucleic acids, proteins, and metabolites, as well as their interactions, and, thus, holds great promise for gaining mechanistic insights into a variety of diseases, including diseases of the heart [5,6]. Following sequencing of the human genome, it became clear that genomic information alone was insufficient to understand biological functions.…”

Section: Introductionmentioning

confidence: 99%

Top-down Proteomics: Technology Advancements and Applications to Heart Diseases

Cai

Tucholski

Gregorich

et al. 2016

Expert Review of Proteomics

129

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Introduction Diseases of the heart are a leading cause of morbidity and mortality for both men and women worldwide, and impose significant economic burdens on the healthcare systems. Despite substantial effort over the last several decades, the molecular mechanisms underlying diseases of the heart remain poorly understood. Areas covered Altered protein post-translational modifications (PTMs) and protein isoform switching are increasingly recognized as important disease mechanisms. Top-down high-resolution mass spectrometry (MS)-based proteomics has emerged as the most powerful method for the comprehensive analysis of PTMs and protein isoforms. Here, we will review recent technology developments in the field of top-down proteomics, as well as highlight recent studies utilizing top-down proteomics to decipher the cardiac proteome for the understanding of the molecular mechanisms underlying diseases of the heart. Expert commentary Top-down proteomics is a premier method for the global and comprehensive study of protein isoforms and their PTMs, enabling the identification of novel protein isoforms and PTMs, characterization of sequence variations, and quantification of disease-associated alterations. Despite significant challenges, continuous development of top-down proteomics technology will greatly aid the dissection of the molecular mechanisms underlying diseases of the hearts for the identification of novel biomarkers and therapeutic targets.

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“…Proteomic strategies provide us with a means to index the proteins present, quantify levels, determine function, and explore interactions. 15 This review will not concentrate on mass spectrometry technological advances that are well described in other reviews. 15 Rather, we will focus on how sample preparation and labeling protocols have changed to increase the likelihood of cataloguing the cardiac ECM proteome.…”

Section: Introductionmentioning

confidence: 99%

Using Extracellular Matrix Proteomics to Understand Left Ventricular Remodeling

Lindsey

Weintraub

Lange

2012

Circ Cardiovasc Genet

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Survival following myocardial infarction (MI) has improved substantially over the last 40 years; however, the incidence of subsequent congestive heart failure has dramatically increased as a consequence. Discovering plasma markers that signify adverse cardiac remodeling may allow high-risk patients to be recognized earlier and may provide an improved way to assess treatment efficacy. Alterations in extracellular matrix (ECM) regulate cardiac remodeling following MI and potentially provide a large array of candidate indicators. The field of cardiac proteomics has progressed rapidly over the past 20 years, since publication of the first two-dimensional electrophoretic gels of left ventricle proteins. Proteomic approaches are now routinely utilized to better understand how the left ventricle responds to injury. In this review, we will discuss how methods have developed to allow comprehensive evaluation of the ECM proteome. We will explain how ECM proteomic data can be used to predict adverse remodeling for an individual patient and highlight future directions. Although this review will focus on the use of ECM proteomics to better understand post-MI remodeling responses, these approaches have applicability to a wide-range of cardiac pathologies, including pressure overload hypertrophy, viral myocarditis, and non-ischemic heart failure.

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Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Proteomics approaches to the systems biology of cardiovascular diseases

Cited by 30 publications

References 71 publications

Proteomics in heart failure: top-down or bottom-up?

Proteomics in heart failure: top-down or bottom-up?

Top-down Proteomics: Technology Advancements and Applications to Heart Diseases

Using Extracellular Matrix Proteomics to Understand Left Ventricular Remodeling

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