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Published on: January 28, 2020
Patients with Coronary Artery Disease Have Lower Levels of Antibody to Heat-Stressed Fibroblast Derived Proteins,
Azin Aghamajidi1,2, Hesam Babaei Khameneh1, Narges Amirjamshidi1
1Students Research Committee, School of Medicine, Babol University of Medical Sciences, Babol, Iran.
Insights
Heat-stressed fibroblasts produce proteins that can be used to diagnose coronary artery disease (CAD). Anti-heat shock protein (HSP) antibodies are higher in healthy individuals, suggesting a diagnostic role for these fibroblast-derived HSPs in CAD.
Area of Science:
- Biochemistry
- Immunology
- Cardiovascular Medicine
Background:
- Cellular stress response is integral to coronary artery disease (CAD) pathophysiology.
- Fibroblasts, comprising 60-70% of cardiac cells, are vital for cardiovascular function.
- Targeting cellular stress offers novel diagnostic and therapeutic strategies for CAD.
Purpose of the Study:
- To investigate the potential therapeutic and diagnostic applications of proteins derived from heat-stressed fibroblasts in CAD patients.
- To analyze the immunogenic properties of fibroblast-derived heat shock proteins (HSPs) and their correlation with CAD.
- To evaluate anti-HSP antibody levels as a potential biomarker for CAD diagnosis.
Main Methods:
- Fibroblasts were cultured under heat stress conditions.
- Protein production was analyzed using SDS-PAGE and 2D electrophoresis.
- Serum immunoglobulin-G (IgG) levels against HSPs were measured via ELISA in 50 CAD patients and 50 normal subjects.
- Diagnostic accuracy was assessed using odds ratio and ROC analysis, comparing anti-HSP antibodies with exercise stress testing (EST).
Main Results:
- Heat-stressed fibroblasts yielded higher total protein levels and exhibited a necrotic death pattern in 1.06% of cells.
- A 70 kDa protein band was identified in stressed cell supernatants.
- Anti-HSP antibody levels were significantly higher in non-CAD individuals compared to CAD patients (p < 0.05).
- Anti-HSP antibodies demonstrated a specificity of 74% and sensitivity of 64% for CAD diagnosis, comparable to EST's 66% sensitivity.
Conclusions:
- Fibroblast-derived HSPs show promise for CAD diagnosis and management through antibody detection.
- Elevated anti-HSP antibodies in non-CAD individuals suggest a potential protective role or diagnostic marker.
- Further research into fibroblast-derived HSPs could lead to novel clinical approaches for CAD.
Abstract:
Cellular stress response plays an important role in the pathophysiology of coronary artery disease (CAD). Inhibition of cellular stress may provide a novel clinical approach regarding the diagnosis and treatment of CAD. Fibroblasts constitute 60-70% of cardiac cells and have a crucial role in cardiovascular function. Hence, the aim of this study was to show a potential therapeutic application of proteins derived from heat-stressed fibroblast in CAD patients. Fibroblasts were isolated from the foreskin and cultured under heat stress conditions. Surprisingly, 1.06% of the cells exhibited a necrotic death pattern. Furthermore, heat-stressed fibroblasts produced higher level of total proteins than control cells. In SDS-PAGE analysis, a 70 kDa protein band was observed in stressed cell culture supernatants which appeared as two acidic spots with close pI in the two-dimensional electrophoresis. To evaluate the immunogenic properties of fibroblast-derived heat shock proteins (HSPs), the serum immunoglobulin-G (IgG) was measured by ELISA in 50 CAD patients and 50 normal subjects who had been diagnosed through angiography. Interestingly, the level of anti-HSP antibody was significantly higher in non-CAD individuals in comparison with the patient's group (p < 0.05). The odds ratio for CAD was 5.06 (95%CI = 2.15-11.91) in cut-off value of 30 AU/mL of anti-HSP antibody. Moreover, ROC analysis showed that anti-HSP antibodies had a specificity of 74% and a sensitivity of 64%, which is almost equal to 66% sensitivity of exercise stress test (EST) as a CAD diagnostic method. These data revealed that fibroblast-derived HSPs are suitable for the diagnosis and management of CAD through antibody production.
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