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Vascular inflammation and low-density lipoproteins: is cholesterol the link? A lesson from the clinical trials
Alberico Luigi Catapano1,2, Angela Pirillo3, Giuseppe Danilo Norata1,4
1Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
Insights
Lowering low-density lipoprotein (LDL) cholesterol is crucial for reducing atherosclerosis by targeting inflammation. Lipid-lowering therapies improve cardiovascular outcomes by reducing vascular inflammation and LDL accumulation.
Area of Science:
- Cardiovascular Science
- Inflammation Biology
- Lipid Metabolism
Background:
- Atherosclerosis pathogenesis traditionally studied LDL and inflammation separately.
- Recent evidence suggests a common platform linking LDL cholesterol and inflammation.
- This review is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk.
Purpose of the Study:
- To explore the interconnected roles of LDL cholesterol and inflammation in atherosclerosis.
- To discuss how lipid-lowering therapies impact inflammatory processes.
- To highlight the importance of reducing LDL levels for cardiovascular health.
Main Methods:
- Review of existing literature on LDL, inflammation, and atherosclerosis.
- Analysis of studies on lipid-lowering therapies (statins, ezetimibe) and their effects on inflammatory markers.
- Consideration of mendelian randomization studies regarding C-reactive protein (CRP).
Main Results:
- Elevated LDL promotes endothelial dysfunction and inflammation, increasing cardiovascular risk.
- Lipid-lowering therapies, like statins, reduce inflammatory markers (e.g., CRP) and improve endothelial function.
- Beneficial effects of LDL reduction on inflammation are most pronounced in patients with baseline inflammation, irrespective of the drug's mechanism.
Conclusions:
- A strong link exists between cholesterol accumulation and vascular inflammation.
- Decreasing LDL cholesterol levels is a primary strategy for improving cardiovascular outcomes.
- Targeting inflammation through LDL reduction is key in managing atherosclerosis.
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.