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

Alberico Luigi Catapano, Angela Pirillo, Giuseppe Danilo Norata

Research output: Contribution to journalReview articlepeer-review

Abstract

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. Linked Articles: This article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc.

Original languageEnglish
Pages (from-to)3973-3985
Number of pages13
JournalBritish Journal of Pharmacology
Volume174
Issue number22
DOIs
Publication statusPublished - Nov 1 2017

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Vascular inflammation and low-density lipoproteins: is cholesterol the link? A lesson from the clinical trials'. Together they form a unique fingerprint.

Cite this