Native low density lipoproteins (n-LDL) and oxidized low density lipoproteins (Ox-LDL) play a central role in atherogenesis and possess a wide variety of biological properties. We investigated whether n-LDL or Ox-LDL modulate cyclooxygenase-1 and -2 (Cox-1 and Cox-2) expression and prostaglandins release in human endothelial cells via an MAPK-dependent pathway. HUVECs were incubated in the presence of n-LDL or Ox-LDL (30 micro g/ml for both) for 2-15 h. Real-time PCR, western blotting and immunocytochemistry were used to investigate Cox-1 and Cox-2 expression. N-LDL and Ox-LDL induced Cox-2 expression in a time- and dose-dependent manner. The Cox-2 protein was strongly induced 2 h after exposure to n-LDL or Ox-LDL, the induction was maximal after 4 h and sustained for at least 8 h. The effect was specific for Cox-2, as Cox-1 expression was not modulated either by n-LDL or by Ox-LDL. The induction of Cox-2 expression was mainly dependent on the activation of p38 MAPK. Transient transfection analysis using a Cox-2 promoter showed that n-LDL and Ox-LDL exert their effects at the transcriptional level via NF-kappaB and CREB activation. N-LDL and Ox-LDL increased PGE2 release in a Cox-2-dependent manner while TXA2 and PGI2 release were not affected either by n-LDL or Ox-LDL. The finding that n-LDL and Ox-LDL induces Cox-2 in human endothelial cells through a p38 MAPK, NF-kappaB, CREB dependent pathway thus modulating PGE2 release, suggests a new mechanism by which these lipoproteins induce endothelial dysfunction, sustaining inflammatory processes in the arterial wall.

Native LDL and oxidized LDL modulate cyclooxygenase-2 expression in HUVECs through a p38-MAPK, NF-kappaB, CRE dependent pathway and affect PGE2 synthesis / G.D. Norata, A. Pirillo, F. Pellegatta, H. Inoue, A.L. Catapano. - In: INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE. - ISSN 1107-3756. - 14:3(2004 Sep), pp. 353-359.

Native LDL and oxidized LDL modulate cyclooxygenase-2 expression in HUVECs through a p38-MAPK, NF-kappaB, CRE dependent pathway and affect PGE2 synthesis

G.D. Norata
Primo
;
A.L. Catapano
Ultimo
2004

Abstract

Native low density lipoproteins (n-LDL) and oxidized low density lipoproteins (Ox-LDL) play a central role in atherogenesis and possess a wide variety of biological properties. We investigated whether n-LDL or Ox-LDL modulate cyclooxygenase-1 and -2 (Cox-1 and Cox-2) expression and prostaglandins release in human endothelial cells via an MAPK-dependent pathway. HUVECs were incubated in the presence of n-LDL or Ox-LDL (30 micro g/ml for both) for 2-15 h. Real-time PCR, western blotting and immunocytochemistry were used to investigate Cox-1 and Cox-2 expression. N-LDL and Ox-LDL induced Cox-2 expression in a time- and dose-dependent manner. The Cox-2 protein was strongly induced 2 h after exposure to n-LDL or Ox-LDL, the induction was maximal after 4 h and sustained for at least 8 h. The effect was specific for Cox-2, as Cox-1 expression was not modulated either by n-LDL or by Ox-LDL. The induction of Cox-2 expression was mainly dependent on the activation of p38 MAPK. Transient transfection analysis using a Cox-2 promoter showed that n-LDL and Ox-LDL exert their effects at the transcriptional level via NF-kappaB and CREB activation. N-LDL and Ox-LDL increased PGE2 release in a Cox-2-dependent manner while TXA2 and PGI2 release were not affected either by n-LDL or Ox-LDL. The finding that n-LDL and Ox-LDL induces Cox-2 in human endothelial cells through a p38 MAPK, NF-kappaB, CREB dependent pathway thus modulating PGE2 release, suggests a new mechanism by which these lipoproteins induce endothelial dysfunction, sustaining inflammatory processes in the arterial wall.
atherosclerosis ; lipoproteins ; cyclooxygenase ; p38 MAPK ; NF-kappaB ; CREB ; PGE2
Settore BIO/14 - Farmacologia
set-2004
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/9013
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