Abstract 323: Increased Levels of Plasma Soluble Sema4D in Patients with Heart Failure
Introduction 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 cardiovascular disorders have not been reported.
Hypothesis We hypothesized that plasma soluble Sema4D levels increases in patients with heart failure (HF) and that such an increase reflects T-cell and/or platelet activation.
Methods We established an ELISA method and detected soluble Sema4D levels in human plasma, and evaluated the effect of estradiol on Sema4D shedding in platelets with collagen-induced aggregation. Percentage of Sema4Dhigh T cells, B cells and platelets in HF patients and healthy controls was detected with flow cytometry.
Results In healthy controls, plasma Sema4D levels were higher in men than women (5.15 ± 3.30, n=63, vs. 4.19 ± 2.39 ng/mL, n=63, P<0.05), and cleavage of Sema4D in platelets activated by collagen was inhibited by estradiol. 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 Sema4Dhigh CD3+ (P<0.01), CD4+ (P<0.001), and CD8+ (P<0.01) T-cells in samples from HF patients, but no change in B cells and platelet Sema4D expression levels.
Conclusions Plasma Sema4D levels are increased in HF patients, especially in those who also have diabetes. There was an accompanying increase in the Sema4Dhigh population of T-cells, suggesting a potential role of these T-cells in heart failure.
- © 2013 by American Heart Association, Inc.