Dehydroepiandrosterone (DHEA) inhibition of monocyte binding by vascular endothelium is associated with sialylation of neural cell adhesion molecule

Curatola AM, Huang K, Naftolin F.
Source: Regenerative Med
Publication Date: (2012)
Issue: 19(1): 86-91
Research Area:
Basic Research
Cells used in publication:
Endothelial, coronary art, human (HCAEC)
Species: human
Tissue Origin: artery
RATIONALE: Adhesion of monocytes to vascular endothelium is necessary for atheroma formation. This adhesion requires binding of endothelial neural cell adhesion molecule (NCAM) to monocyte NCAM. NCAM:NCAM binding is blocked by sialylation of NCAM (polysialylated NCAM; PSA-NCAM). Since estradiol (E2) and dihydrotestosterone (DHT) induced PSA-NCAM and decreased monocyte adhesion, in consideration of possible clinical applications we tested whether their prohormone dehydroepiandrosterone (DHEA) has similar effects. EXPERIMENTAL: (1) DHEA was administered to cultured human coronary artery endothelial cells (HCAECs) from men and women. Monocyte binding was assessed using fluorescence-labeled monocytes. (2) HCEACs were incubated with E2, DHT, DHEA alone, or with trilostane, fulvestrant or flutamide. Expression of PSA-NCAM was assessed by immunohistochemistry and Western blotting. RESULTS: Dehydroepiandrosterone inhibited monocyte adhesion to HCAECs by =50% (P < .01). Fulvestrant or flutamide blockade of DHEA's inhibition of monocyte binding appeared to be gender dependent. The DHEA-induced expression of PSA-NCAM was completely blocked by trilostane. CONCLUSIONS: In these preliminary in vitro studies, DHEA increased PSA-NCAM expression and inhibited monocyte binding in an estrogen- and androgen receptor-dependent manner. Dehydroepiandrosteroneappears to act via its end metabolites, E2 and DHT. Dehydroepiandrosterone could furnish clinical prevention against atherogenesis and arteriosclerosis.