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Increased levels of plasma soluble Sema4D in patients with heart failure
Qiongyu Lu1, Ningzheng Dong, Qi Wang
1Cyrus Tang Hematology Center, Soochow University, Suzhou, Jiangsu, China.
Abstract:
Semaphorin 4D (Sema4D/CD100) is a 150-kDa transmembrane glycoprotein expressed by platelets and T-cells. When these cells are activated, Sema4D is cleaved proteolytically, generating a biologically active 120-kDa fragment (soluble Sema4D) capable of targeting receptors on platelets, B-cells, endothelial cells and tumor cells. However, its plasma levels and significance in heart failure (HF) have not been reported. In this study, we established an ELISA and detected soluble Sema4D in human plasma. In healthy controls, plasma Sema4D levels were higher in men than women (5.15±3.30 ng/mL, n = 63, vs. 4.19±2.39 ng/mL, n = 63, P<0.05). In HF patients, plasma Sema4D levels were significantly higher than those in healthy controls (8.94±5.89 ng/mL, n = 157 vs. 4.67±2.99 ng/mL, n = 126, P<0.0001) with the highest levels being in HF patients with diabetes mellitus (DM) (10.45±5.76 ng/mL, n = 40). We also found that there was a higher percentage of Sema4D(high) CD3(+) (P<0.01), CD4(+) (P<0.001), and CD8(+) (P<0.01) T-cells in samples from HF patients, but no changes in Sema4D expression levels in B cells and platelets. Therefore, our investigation shows that plasma Sema4D levels are increased in HF patients, especially in those who also have diabetes. There was an accompanying increase in the Sema4D(high) population of T-cells, suggesting a potential role of these T-cells in heart failure.
Insights
Plasma levels of Semaphorin 4D (Sema4D) are elevated in heart failure (HF) patients, particularly those with diabetes. Increased Sema4D expression on T-cells suggests their involvement in HF pathogenesis.
Area of Science:
- Cardiovascular Biology
- Immunology
- Biochemistry
Background:
- Semaphorin 4D (Sema4D/CD100) is a transmembrane glycoprotein involved in cell signaling.
- Soluble Sema4D is generated from activated platelets and T-cells.
- The role and plasma levels of Sema4D in heart failure (HF) were previously unknown.
Purpose of the Study:
- To investigate plasma levels of soluble Sema4D in human heart failure.
- To explore the association between Sema4D levels and clinical characteristics, including diabetes mellitus (DM).
- To examine Sema4D expression on immune cells in heart failure patients.
Main Methods:
- Developed an Enzyme-Linked Immunosorbent Assay (ELISA) to quantify soluble Sema4D in human plasma.
- Compared plasma Sema4D levels between healthy controls and HF patients.
- Analyzed Sema4D expression on T-cells, B-cells, and platelets using flow cytometry.
Main Results:
- Plasma Sema4D levels were significantly higher in HF patients compared to healthy controls.
- HF patients with diabetes mellitus exhibited the highest plasma Sema4D levels.
- An increased percentage of Sema4D(high) T-cells (CD3+, CD4+, CD8+) was observed in HF patients.
Conclusions:
- Plasma soluble Sema4D is a potential biomarker for heart failure.
- Elevated Sema4D levels, especially in HF patients with DM, highlight a link between inflammation and disease severity.
- Increased Sema4D expression on T-cells suggests a role for these cells in the pathophysiology of heart failure.
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