Aim: 

Oxidized LDL (oxLDL) is an etiologic factor for atherosclerosis impairing physiological balance of vasoactive compounds. Prostacyclin (PGI₂) and thromboxane (TXA₂) are prostanoids with opposing effects involved on vascular homeostasis. This work is focused on the effect of oxLDL on prostanoids production, and the potential protective role of estradiol in human umbilical artery endothelial cells (HUAEC).

Methods: 

Primary HUAEC were exposed to desired treatments for 24 hours. The stable metabolites of PGI₂ and TXA₂, 6-keto-prostaglandin-F_2a and TXB₂ respectively, were determined in culture supernatants by ELISA. Prostacyclin synthase (PGIS), cyclooxigenase-1 (COX-1) and -2 (COX-2) protein expressions were evaluated by immunoblotting.

Results: 

oxLDL (100mg/mL) increased TXA₂ and PGI₂ production. Estradiol (1 nM) slightly reduced both mediators, without altering the effect of oxLDL. oxLDL strongly increases COX-2 and reduces PGIS protein expression, without affecting COX-1.

Conclusion: 

Increased PGI₂ and TXA₂ induced by oxLDL are due to the overexpression of COX-2, whereas estradiol does not exert any effect. PGIS could act as a regulator key in this pathway.

Supported by Ministerio Ciencia e Innovación, ISCIII (FIS 06/0589, FIS 08/0634, RED HERACLES RD06/0009) and Consellería Sanidad, GV (AP 09/2007, AP 121/08). PJO holds a post-doc position, and AS is a FPI fellow (BFPI 06/145), both from Consellería de Educación, Generalitat Valenciana, Spain.