Gene interactions and pathways from curated databases and text-mining
Atherosclerosis 2006, PMID: 16212965

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-kappaB.

Gómez-Hernández, Almudena; Martín-Ventura, Jose Luis; Sánchez-Galán, Eva; Vidal, Cristina; Ortego, Mónica; Blanco-Colio, Luis Miguel; Ortega, Luis; Tuñón, José; Egido, Jesús

OBJECTIVE

Prostaglandin E2 (PGE(2), 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-kappaB) 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-kappaB and COX-2, mPGES-1 and EPs proteins were colocalized in the plaque's cells. In cytokine-treated cultured THP-1, the NF-kappaB 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-kappaB 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-kappaB inhibitors and/or EPs antagonists could represent a novel therapeutic approach to the treatment of plaque instability and rupture.

Diseases/Pathways annotated by Medline MESH: Carotid Artery Diseases
Document information provided by NCBI PubMed

Text Mining Data

EPs — nuclear factor-kappaB (NF-kappaB): " 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-kappaB) inhibitors on COX-2, mPGES-1 and EPs expression in cultured monocytic cells ( THP-1 ) "

EPs — mPGES-1: " 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-kappaB) inhibitors on COX-2, mPGES-1 and EPs expression in cultured monocytic cells ( THP-1 ) "

EPs — COX-2: " 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-kappaB) inhibitors on COX-2, mPGES-1 and EPs expression in cultured monocytic cells ( THP-1 ) "

mPGES-1 — nuclear factor-kappaB (NF-kappaB): " 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-kappaB) inhibitors on COX-2, mPGES-1 and EPs expression in cultured monocytic cells ( THP-1 ) "

mPGES-1 — COX-2: " 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-kappaB) inhibitors on COX-2, mPGES-1 and EPs expression in cultured monocytic cells ( THP-1 ) "

COX-2 — nuclear factor-kappaB (NF-kappaB): " 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-kappaB) inhibitors on COX-2 , mPGES-1 and EPs expression in cultured monocytic cells ( THP-1 ) "

THP-1 → NF-kappaB: " In cytokine treated cultured THP-1 , the NF-kappaB 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 "

mPGES-1 → NF-kappaB: " In cytokine treated cultured THP-1, the NF-kappaB 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 "

COX-2 → NF-kappaB: " In cytokine treated cultured THP-1, the NF-kappaB 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 "

Manually curated Databases

No curated data.