A still growing bulk of evidence underlies the multifaceted biochemical properties of oxysterols, several of them of clear relevance to human pathophysiology. Taken up by cells through both vesicular and non vesicular ways or often generated intracellularly, oxysterols contribute to modulate the inflammatory response of a given tissue but also cell viability, metabolism and function. The signaling pathways and the transcription factors whose activation they can influence, often through redox-mediated reactions, are quite a number. Moreover, the outcome of the complex network of intracellular reactions promoted by oxysterols appears to be largely dependent upon specific features and dynamic conditions of the cellular and tissue environment but also on their actual concentration in the site of action. Here focus was given to their potential implication in the advanced progression of atherosclerosis, whose hypercholesterolemia is a recognized primary risk factor. A significant contribution to the possible rupture of atherosclerotic plaque could be provided by defined oxysterols, in particular 27-hydroxycholesterol. Indeed, the latter oxysterol was shown in a promonocytic cell line to amplify the inflammatory reaction and activate several pathways leading to a marked up-regulation of metalloproteases, the key enzymes involved in cap matrix degradation and weakening.

Oxysterols, metalloproteases and atherosclerotic plaque rupture.

GARGIULO, Simona;ROSSIN, DANIELA;TESTA, GABRIELLA;GAMBA, Paola Francesca;LEONARDUZZI, Gabriella Marisa;POLI, Giuseppe
2017-01-01

Abstract

A still growing bulk of evidence underlies the multifaceted biochemical properties of oxysterols, several of them of clear relevance to human pathophysiology. Taken up by cells through both vesicular and non vesicular ways or often generated intracellularly, oxysterols contribute to modulate the inflammatory response of a given tissue but also cell viability, metabolism and function. The signaling pathways and the transcription factors whose activation they can influence, often through redox-mediated reactions, are quite a number. Moreover, the outcome of the complex network of intracellular reactions promoted by oxysterols appears to be largely dependent upon specific features and dynamic conditions of the cellular and tissue environment but also on their actual concentration in the site of action. Here focus was given to their potential implication in the advanced progression of atherosclerosis, whose hypercholesterolemia is a recognized primary risk factor. A significant contribution to the possible rupture of atherosclerotic plaque could be provided by defined oxysterols, in particular 27-hydroxycholesterol. Indeed, the latter oxysterol was shown in a promonocytic cell line to amplify the inflammatory reaction and activate several pathways leading to a marked up-regulation of metalloproteases, the key enzymes involved in cap matrix degradation and weakening.
Metabolic stress and redox regulation
Berlino
21-23 giugno 2017
108
S13
S13
Gargiulo, Simona; Rossin, Daniela; Testa, Gabriella; Gamba, Paola; Leonarduzzi, Gabriella; Poli, Giuseppe
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1644210
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