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Published on: January 16, 2019
Molecular basis of coronary artery dilation and aneurysms in patients with Kawasaki disease based on differential
Wanting Liu1, Chaowu Liu2, Li Zhang3
1Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
Insights
Researchers identified key proteins in children with Kawasaki disease (KD) complications, coronary artery dilation (CAD) and coronary artery aneurysms (CAA). Five proteins (MBL2, CFH, KNG1, SERPINC1, FN1) may help distinguish between these serious cardiac conditions.
Area of Science:
- Cardiology
- Immunology
- Biochemistry
Background:
- Kawasaki disease (KD) is a leading cause of acquired pediatric heart disease.
- Coronary artery dilation (CAD) and coronary artery aneurysms (CAA) are significant KD complications.
- Understanding differential protein expression is crucial for differentiating KD complications.
Purpose of the Study:
- To identify differentially expressed serum proteins between KD patients with CAD and CAA.
- To elucidate the underlying biological mechanisms distinguishing these KD complications.
- To validate potential protein biomarkers for differentiating CAD and CAA.
Main Methods:
- Proteomic analysis using isobaric tags for relative and absolute quantitation (iTRAQ).
- Bioinformatic analysis of differentially expressed proteins using ClueGo and ReactomeFIViz.
- Validation of selected proteins by western blotting.
Main Results:
- Identified 87 and 65 significantly differentially expressed proteins in KD patients with CAD and CAA, respectively, compared to controls.
- Protein variations were linked to wound healing, lipoprotein, and cholesterol metabolism pathways.
- Five proteins (MBL2, CFH, KNG1, SERPINC1, FN1) associated with immunity, inflammation, and metabolism were identified and validated.
Conclusions:
- Mannose binding lectin 2 (MBL2), complement factor H (CFH), kininogen 1 (KNG1), serpin family C member 1 (SERPINC1), and fibronectin 1 (FN1) may serve as potential biomarkers for distinguishing CAD and CAA in Kawasaki disease.
- These proteins play key roles in immunity, inflammation, and metabolism, offering novel insights into KD pathogenesis.
- Further research is warranted to confirm the diagnostic and prognostic value of these protein markers.
Abstract:
Kawasaki disease (KD) is an acquired cardiac disease with a high incidence that affects children. KD has various complications, including coronary artery dilation (CAD) and coronary artery aneurysms (CAA). The identification of differentially expressed proteins and the underlying mechanisms may be the key to understanding differences between these KD complications. In the present study, isobaric tags for relative and absolute quantitation were used to identify variations in serum proteins between KD patients with CAD and CAA. In total, 87 (37 upregulated and 50 downregulated) and 65 (33 upregulated and 32 downregulated) significantly differentially‑expressed proteins were identified in comparisons between control samples (healthy individuals) and those obtained from patients with KD and with CAD or CAA. Investigation into the underlying biological process revealed that variations between the two complications were associated with the wound healing response, as well as lipoprotein‑ and cholesterol‑associated processes. Important proteins involved in the formation of the wound healing signaling network were identified via enriched biological processes and pathway analysis using ClueGo and ReactomeFIViz software. In the present study, 5 significantly differentially‑expressed proteins, including mannose binding lectin 2 (MBL2), complement factor H (CFH), kininogen 1 (KNG1), serpin family C member 1 (SERPINC1) and fibronectin 1 (FN1), were selected and confirmed by western blotting. Analysis indicated that these proteins were associated to immunity, inflammation and metabolism, serving a key role within each module, which has never been reported previously. The present study proposed that MBL2, CFH, KNG1, SERPINC1 and FN1 may be a potentially excellent indicator group for distinguishing the two major KD complications, CAD and CAA.
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