Vascular inflammation and low-density lipoproteins: Is cholesterol the link? A lesson from the clinical trials

© 2017 The British Pharmacological Society. For long time, the role of LDL and inflammation in the pathogenesis of atherosclerosis have been studied independently from each other and only more recently a common platform has been suggested. Accumulation of excess cholesterol due to the presence of in...

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Main Authors: Catapano, A., Pirillo, A., Norata, Giuseppe
Format: Journal Article
Published: John Wiley & Sons 2017
Online Access:http://hdl.handle.net/20.500.11937/55932
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author Catapano, A.
Pirillo, A.
Norata, Giuseppe
author_facet Catapano, A.
Pirillo, A.
Norata, Giuseppe
author_sort Catapano, A.
building Curtin Institutional Repository
collection Online Access
description © 2017 The British Pharmacological Society. For long time, the role of LDL and inflammation in the pathogenesis of atherosclerosis have been studied independently from each other and only more recently a common platform has been suggested. Accumulation of excess cholesterol due to the presence of increased circulating LDL promotes endothelium dysfunction and activation, which is associated with increased production of pro-inflammatory cytokines, overexpression of adhesion molecules, chemokines and C-reactive protein (CRP), increased generation of reactive oxygen species and reduction of nitric oxide levels and bioavailability. All these processes favour the progressive infiltration of inflammatory cells within the arterial wall where cholesterol accumulates, both extracellularly and intracellularly, and promotes vascular inflammation. According to this, lipid-lowering therapies should improve inflammation and, indeed, statins decrease circulating inflammatory markers such as CRP and improve endothelial function and plaque burden. Pleiotropic activities have been proposed to explain this effect. However, mendelian randomization studies ruled out a direct role for CRP on coronary artery disease and studies with other lipid lowering drugs, such as ezetimibe showed that the beneficial effect of LDL-cholesterol-lowering therapies on systemic inflammatory status, as monitored by changes in CRP plasma levels, could be achieved, independently of the mechanism of action, only in patients presenting with baseline inflamed conditions. These observations strengthen the direct link between cholesterol and inflammation and indicate that decreasing LDL levels is one of the key goals for improving cardiovascular outcome.
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spelling curtin-20.500.11937-559322017-09-13T16:10:51Z Vascular inflammation and low-density lipoproteins: Is cholesterol the link? A lesson from the clinical trials Catapano, A. Pirillo, A. Norata, Giuseppe © 2017 The British Pharmacological Society. For long time, the role of LDL and inflammation in the pathogenesis of atherosclerosis have been studied independently from each other and only more recently a common platform has been suggested. Accumulation of excess cholesterol due to the presence of increased circulating LDL promotes endothelium dysfunction and activation, which is associated with increased production of pro-inflammatory cytokines, overexpression of adhesion molecules, chemokines and C-reactive protein (CRP), increased generation of reactive oxygen species and reduction of nitric oxide levels and bioavailability. All these processes favour the progressive infiltration of inflammatory cells within the arterial wall where cholesterol accumulates, both extracellularly and intracellularly, and promotes vascular inflammation. According to this, lipid-lowering therapies should improve inflammation and, indeed, statins decrease circulating inflammatory markers such as CRP and improve endothelial function and plaque burden. Pleiotropic activities have been proposed to explain this effect. However, mendelian randomization studies ruled out a direct role for CRP on coronary artery disease and studies with other lipid lowering drugs, such as ezetimibe showed that the beneficial effect of LDL-cholesterol-lowering therapies on systemic inflammatory status, as monitored by changes in CRP plasma levels, could be achieved, independently of the mechanism of action, only in patients presenting with baseline inflamed conditions. These observations strengthen the direct link between cholesterol and inflammation and indicate that decreasing LDL levels is one of the key goals for improving cardiovascular outcome. 2017 Journal Article http://hdl.handle.net/20.500.11937/55932 10.1111/bph.13805 John Wiley & Sons unknown
spellingShingle Catapano, A.
Pirillo, A.
Norata, Giuseppe
Vascular inflammation and low-density lipoproteins: Is cholesterol the link? A lesson from the clinical trials
title Vascular inflammation and low-density lipoproteins: Is cholesterol the link? A lesson from the clinical trials
title_full Vascular inflammation and low-density lipoproteins: Is cholesterol the link? A lesson from the clinical trials
title_fullStr Vascular inflammation and low-density lipoproteins: Is cholesterol the link? A lesson from the clinical trials
title_full_unstemmed Vascular inflammation and low-density lipoproteins: Is cholesterol the link? A lesson from the clinical trials
title_short Vascular inflammation and low-density lipoproteins: Is cholesterol the link? A lesson from the clinical trials
title_sort vascular inflammation and low-density lipoproteins: is cholesterol the link? a lesson from the clinical trials
url http://hdl.handle.net/20.500.11937/55932