Abstract
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 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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Abbreviations
- HF:
-
Heart failure
- MS:
-
Mass spectrometry
- PTMs:
-
Post-translational modifications
- 2DGE:
-
Two-dimensional gel electrophoresis
- m/z :
-
Mass-to-charge ratio
- MS/MS:
-
Tandem mass spectrometry
- MALDI:
-
Matrix-assisted laser desorption/ionization
- ESI:
-
Electrospray ionization
- LC:
-
Liquid chromatography
- CID:
-
Collision-induced dissociation
- AP:
-
Affinity purification
- ECD:
-
Electron capture dissociation
- SNO:
-
S-nitrosylation
- cTnI:
-
Cardiac troponin I
- SHR:
-
Spontaneously hypertensive rat
- WKY:
-
Wistar-Kyoto
- iTRAQ:
-
Isotope tags for relative and absolute quantification
- MI:
-
Myocardial infarction
- SILAC:
-
Stable isotope labeling by amino acids in cell culture
- TAC:
-
Transverse aortic constriction
- MW:
-
Molecular weight
- MDLC:
-
Multi-dimensional liquid chromatography
- cMyBP-C:
-
Cardiac myosin binding protein-C
- TOF:
-
Time-of-flight
- Q-TOF:
-
Quadrupole-time-of-flight
- HCD:
-
High-energy collision dissociation
- IRMPD:
-
Infrared multiphoton dissociation
- UVPD:
-
Ultraviolet photodissociation
- PSD:
-
Post-source decay
- ETD:
-
Electron transfer dissociation
- GELFrEE:
-
Gel-eluted liquid fraction entrapment electrophoresis
- IMAC:
-
Immobilized-metal affinity chromatography
- TMT:
-
Tandem mass tag
- FTMS:
-
Fourier-transform mass spectrometry
- iCAT:
-
Isotope-coded affinity tag
- HDAC:
-
Histone deacetylase
- Tm:
-
Tropomyosin
- XIC:
-
Extracted ion chromatogram
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Acknowledgments
We would like to acknowledge the financial support by the National Institute of Health R01HL096971 and R01HL109810 (to YG). ZG would like to thank the National Institute of Health training grant T32GM008688.
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Gregorich, Z.R., Chang, YH. & Ge, Y. Proteomics in heart failure: top-down or bottom-up?. Pflugers Arch - Eur J Physiol 466, 1199–1209 (2014). https://doi.org/10.1007/s00424-014-1471-9
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DOI: https://doi.org/10.1007/s00424-014-1471-9