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Published on: May 29, 2014
An altered left ventricle protein profile in human ischemic cardiomyopathy revealed in comparative quantitative
Xin Yi1,2,3, Ding-Sheng Jiang4,5,6, Gaoke Feng1,2,3
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China
Insights
Researchers identified key proteins altered in ischemic cardiomyopathy (ICM). These differentially expressed proteins, including C1 inhibitor SERPING1, offer potential new diagnostic and therapeutic targets for heart failure patients.
Area of Science:
- Cardiology
- Proteomics
- Biochemistry
Background:
- Ischemic cardiomyopathy (ICM) is a primary cause of heart failure, stemming from coronary artery disease.
- Identifying and quantifying protein expression changes in ICM patients is crucial for developing better diagnostic and treatment strategies.
Purpose of the Study:
- To identify and quantify differentially expressed proteins in the left ventricles of patients with ICM.
- To explore the molecular mechanisms underlying ICM through proteomic analysis.
Main Methods:
- Quantitative proteomic analysis of left ventricular tissue from 6 ICM patients and 7 normal heart donors using liquid chromatography-tandem mass spectrometry.
- Bioinformatic analyses including gene ontology, pathway mapping, and protein interaction analysis were performed on identified proteins.
Main Results:
- 1723 proteins were quantified, with 104 upregulated and 63 downregulated in ICM patients.
- Altered proteins were associated with extracellular matrix, metabolism, immune response, muscle contraction, cytoskeleton, transcription/translation, and signal transduction.
- C1 inhibitor SERPING1 was found to inhibit complement activation in response to ischemic stimulus.
Conclusions:
- The study identified differentially expressed proteins that are potential novel diagnostic and therapeutic targets for ICM.
- These findings advance the understanding of molecular mechanisms in ICM and highlight SERPING1's role in complement regulation.
Background:
Ischemic cardiomyopathy (ICM) resulting from coronary artery disease is a major cause of heart failure. The identification and quantification of differentially expressed proteins in patients with ICM may potentially lead to more effective diagnostic workup and treatment.
Aims:
Liquid chromatography coupled to tandem mass spectrometry analysis was applied to identify differentially expressed proteins in individuals with ICM.
Methods:
To identify proteins involved in the molecular mechanisms of ICM, we quantitatively analyzed the left ventricular proteome profiles of patients with ICM who had undergone heart transplantation. Liquid chromatography coupled to tandem mass spectrometry, which presents better comprehensiveness and accuracy of quantification than 2‑dimensional electrophoresis, in combination with bioinformatics was applied to analyze cardiac samples and identify proteins that were differentially expressed in the left ventricles of 6 patients with ICM compared with 7 normal heart donors.
Results:
A total of 1723 proteins was successfully quantified in 2 repeated experiments. Out of those, 104 proteins were upregulated and 63 proteins were downregulated in the left ventricles of individuals with ICM. For all these altered proteins, gene ontology (GO) analysis, the Kyoto Encyclopedia of Genes and Genomes pathway mapping, and protein interaction analysis were performed, which showed that most of the proteins were related to the extracellular matrix, metabolism, immune response, muscle contraction, cytoskeleton organization, transcription / translation, and signal transduction. Most importantly, in response to an ischemic stimulus, the C1 inhibitor SERPING1 helped to compensate for increases in complement activation through complement inhibition.
Conclusions:
Collectively, these differentially expressed proteins represent potential novel diagnostic and therapeutic targets for the treatment of patients with ICM.
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