Title of article :
Overexpression of COX-2, Prostaglandin E Synthase-1 and Prostaglandin E Receptors in blood mononuclear cells and plaque of patients with carotid atherosclerosis: Regulation by nuclear factor-κB
Author/Authors :
Almudena G?mez-Hern?ndez، نويسنده , , Jose-Luis Martin-Ventura، نويسنده , , Eva S?nchez-Gal?n، نويسنده , , Cristina Vidal، نويسنده , , M?nica Ortego، نويسنده , , Luis Miguel Blanco-Colio، نويسنده , , José Luis Ortega Priego ، نويسنده , , José Tu??n، نويسنده , , Jesus Egido، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2006
Abstract :
Background and objective
Prostaglandin E2 (PGE2), a product of the cyclooxygenase 2 (COX-2) and membrane-associated Prostaglandin E Synthase (mPGES-1) pathway, has been implicated in the instability of atherosclerotic plaques. We have studied COX-2, mPGES-1 and PGE2 receptors (EPs) expression in peripheral blood mononuclear cells (PBMC) and atherosclerotic plaques of 29 patients with carotid stenosis as well as the effect of different nuclear factor-kappaB (NF-κB) inhibitors on COX-2, mPGES-1 and EPs expression in cultured monocytic cells (THP-1).
Methods
COX-2, mPGES-1 and EP expression was analyzed by RT-PCR (PBMC), immunohistochemistry (plaques) and Western blot (THP-1). PGE2 levels were determined by ELISA (plasma and cell supernatants).
Results
In relation to healthy controls, COX-2, mPGES-1 and EP-3/EP-4 mRNA expression was increased in PBMC from patients. In the inflammatory region of atherosclerotic plaques, an increase of COX-2, mPGES-1 and EPs expression was also observed. Activated NF-κB and COX-2, mPGES-1 and EPs proteins were colocalized in the plaqueʹs cells. In cytokine-treated cultured THP-1, the NF-κB inhibitors parthenolide, Bay 11-7082 and PDTC reduced COX-2, mPGES-1 and EP-1/EP-3/EP-4 expression as well as PGE2 levels. By employing specific agonists and antagonists, we noted that the cytokine- and PGE2-induced metalloproteinase 9 (MMP-9) expression and activity occurs through EP-1/EP-3/EP-4, an effect downregulated by NF-κB inhibitors.
Conclusions
Patients with carotid atherosclerosis depict an overexpression of COX-2, mPGES-1 and EPs simultaneously in the PBMC as well as in the vulnerable region of plaques. The studies in cultured monocytic cells suggest that NF-κB inhibitors and/or EPs antagonists could represent a novel therapeutic approach to the treatment of plaque instability and rupture.
Keywords :
Receptors , Plaque , macrophages , blood , prostaglandins , atherosclerosis
Journal title :
Atherosclerosis
Journal title :
Atherosclerosis