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Glycoproteins identified from heart failure and treatment models
Shuang Yang1, Lijun Chen, Shisheng Sun
1Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Insights
Cardiac resynchronization therapy (CRT) alters serum glycoprotein levels in canine heart failure models. CRT may reverse some changes, suggesting protective pathways reflected in the circulating proteome.
Area of Science:
- Biochemistry
- Cardiology
- Proteomics
Background:
- Conduction abnormalities in heart failure cause dyssynchronous contraction, increasing morbidity and mortality.
- Cardiac resynchronization therapy (CRT) improves cardiac function and reverses ventricular remodeling.
- The molecular mechanisms underlying CRT's benefits are not fully understood.
Purpose of the Study:
- To investigate changes in serum glycoprotein concentrations in a canine model of dyssynchronous heart failure (DHF) before and after CRT.
- To identify specific glycoproteins altered by DHF and responsive to CRT.
- To explore if CRT-induced protective pathways are reflected in the circulating proteome.
Main Methods:
- Utilized a canine model of DHF and CRT.
- Employed two discovery approaches on pooled canine serum samples (normal, DHF, CRT) to analyze overall protein concentration and N-linked glycosites of circulating glycoproteins.
- Verified glycopeptide changes using label-free liquid chromatography-mass spectrometry (LC-MS) on individual canine serum samples.
Main Results:
- Significant alterations in glycoprotein levels were observed in both DHF and CRT groups compared to controls.
- 63 glycopeptides showed substantial increases in DHF and/or CRT conditions.
- Of 32 elevated glycopeptides in DHF, 13 returned to normal levels following CRT treatment.
- Specific glycoproteins like alpha-fetoprotein, alpha-2-macroglobulin, galectin-3-binding protein, and collectin-10 were associated with the DHF and CRT model.
Conclusions:
- CRT significantly impacts the circulating glycoprotein profile in DHF.
- CRT demonstrates a potential to revert specific glycoprotein changes, indicating a restorative effect.
- Circulating glycoproteins serve as potential biomarkers for DHF and indicators of CRT efficacy.
Abstract:
Conduction abnormalities can lead to dyssynchronous contraction, which significantly worsens morbidity and mortality of heart failure. Cardiac resynchronization therapy (CRT) can reverse ventricular remodeling and improve cardiac function. Although the underlying molecular changes are unknown, the use of a canine model of dyssynchronous heart failure (DHF) and CRT has shown that there are global changes across the cardiac proteome. This study determines changes in serum glycoprotein concentration from DHF and CRT compared to normal. We hypothesize that CRT invokes protective or advantageous pathways that can be reflected in the circulating proteome. Two prong discovery approaches were carried out on pooled normal, DHF, and CRT samples composed of individual canine serum to determine the overall protein concentration and the N-linked glycosites of circulating glycoproteins. The level of the glycoproteins was altered in DHF and CRT compared to control sera, with 63 glycopeptides substantially increased in DHF and/or CRT. Among the 32 elevated glycosite-containing peptides in DHF, 13 glycopeptides were reverted to normal level after CRT therapy. We further verify the changes of glycopeptides using label-free LC-MS from individual canine serum. Circulating glycoproteins such as alpha-fetoprotein, alpha-2-macroglobulin, galectin-3-binding protein, and collectin-10 show association to failing heart and CRT treatment model.
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