Targeting the adaptive immune system: new strategies in the treatment of atherosclerosis

Abstract

Atherosclerosis is a lipid-driven chronic inflammatory disease of the arterial wall. Current treatment of atherosclerosis is focused on limiting its risk factors, such as hyperlipidemia or hypertension. However, treatments that target the inflammatory nature of atherosclerosis are still under development. Discovery of novel targets involved in the inflammation of the arterial wall creates opportunities to design new therapeutics that successfully modulate atherosclerosis. Here, we review drug targets that have proven to play pivotal roles in the adaptive immune system in atherosclerosis, and we discuss their potential as novel therapeutics.

Keywords:

• adaptive immune system
• atherosclerosis
• drug discovery
• target identification

Financial & competing interests disclosure

G Nicolaes was supported by a medium investment grant, the Cardiovascular Research Institute Maastricht, the Transnational University Limburg, and Cyttron II FES0908. The authors acknowledge the support from the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation, Dutch Federation of University Medical Centres, the Netherlands Organisation for Health Research and Development and the Royal Netherlands Academy of Sciences for the GENIUS project “Generating the best evidence-based pharmaceutical targets for atherosclerosis” (CVON2011-19).E Lutgens wassupported by the Netherlands Organization for Scientific Research [vici grant], and the Deutsche Forschungsgemeinschaft [SFB914, SFB 1054 and SFB1123. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Atherosclerosis is a lipid-driven chronic inflammatory disease of the arterial wall.

• Current therapies reduce the risk factors of atherosclerosis but do not target its inflammatory nature.

• Both the innate and adaptive immune systems play a pivotal role in the development and progression of atherosclerosis.

• Several proteins involved in the adaptive immune system were validatedin in vivo models as therapeutic targets for the treatment of atherosclerosis.

• A few modulators targeting crucial targets in atherosclerosis are already US FDA-approved or under investigation for the treatment of other inflammatory diseases.

• Blocking co-stimulatory molecules and vaccination seem to be the most promising strategies for the treatment of atherosclerosis.

Notes