Proteomics

Dataset Information

0

Sarcomeric Proteoform Landscape in Ischemic Cardiomyopathy Defined by Top-down Proteomics


ABSTRACT: In ischemic cardiomyopathy (ICM), left ventricular systolic dysfunction leads to reduced blood flow and oxygen supply to the heart. Alterations in sarcomeric protein function and expression play prominent roles in the onset and progression of cardiomyopathies; however, the molecular mechanisms underlying ICM remain poorly defined. Herein, we have implemented a top-down liquid chromatography (LC)-mass spectrometry (MS)-based proteomics method for the simultaneous quantification of sarcomeric protein expression and modifications in non-failing donor (n = 16) compared to end-stage failing ICM (n = 16) human cardiac tissues. Our top-down proteomics platform provided a “bird’s eye view” of proteoform families with high mass accuracy and reproducibility. In addition, quantification of post-translational modifications (PTMs) and expression reveal significant changes in various sarcomeric proteins extracted from ICM tissues. Changes include altered phosphorylation and expression of cardiac troponin I (cTnI) and enigma homolog 2 (ENH2) as well as a marked increase in muscle LIM protein (MLP) and calsarcin-1 phosphorylation in ICM hearts. Our results imply that the contractile apparatus of the sarcomere is severely dysregulated during ICM. Thus, this study is the first to uncover significant molecular changes to multiple sarcomeric proteins in end-stage ischemic heart failure patients using LC-MS-based top-down proteomics.

INSTRUMENT(S): maXis

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Heart

DISEASE(S): Cardiovascular System Disease

SUBMITTER: Emily Chapman  

LAB HEAD: Ying Ge

PROVIDER: PXD038066 | Pride | 2023-02-20

REPOSITORIES: Pride

Dataset's files

Source:
altmetric image

Publications

Defining the Sarcomeric Proteoform Landscape in Ischemic Cardiomyopathy by Top-Down Proteomics.

Chapman Emily A EA   Aballo Timothy J TJ   Melby Jake A JA   Zhou Tianhua T   Price Scott J SJ   Rossler Kalina J KJ   Lei Ienglam I   Tang Paul C PC   Ge Ying Y  

Journal of proteome research 20230217 3


Ischemic cardiomyopathy (ICM) is a prominent form of heart failure, but the molecular mechanisms underlying ICM remain relatively understudied due to marked phenotypic heterogeneity. Alterations in post-translational modifications (PTMs) and isoform switches in sarcomeric proteins play important roles in cardiac pathophysiology. Thus, it is essential to define sarcomeric proteoform landscape to better understand ICM. Herein, we have implemented a top-down liquid chromatography (LC)-mass spectrom  ...[more]

Similar Datasets

2024-01-26 | PXD040488 | Pride
2018-02-19 | PXD006152 | Pride
2020-05-01 | PXD018678 | Pride
2023-05-18 | PXD014826 | Pride
2020-11-30 | PXD019368 | Pride
2021-01-07 | PXD022814 | Pride
2021-09-09 | PXD021261 | Pride
2014-05-02 | E-GEOD-51431 | biostudies-arrayexpress
2013-12-19 | E-GEOD-48166 | biostudies-arrayexpress
2014-07-29 | E-GEOD-57249 | biostudies-arrayexpress