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Understand that atherosclerosis involves multiple pathways related to inflammation.
Understand the limitations of currently available biomarkers.
Learn about new ways of characterising biological processes central to atherogenesis.
Learn about possible future therapeutics for atherosclerosis.
Atherosclerosis is a chronic inflammatory process and both the innate and adaptive immune systems1 play central roles in its initiation and subsequent progression.2 Experimental models have demonstrated that the specific targeting of these biological processes can attenuate plaque formation and, in some instances, even induce regression of disease.3 As a consequence, there has been great interest in the development of clinical immune-modulatory (anti-inflammatory) agents. To date, the results of these endeavours have largely been disappointing. The recently published Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS)4 demonstrated that targeting a particular element of inflammation through inhibition of interleukin (IL)-1β in patients with coronary artery disease reduced occurrence of a composite cardiovascular end point. However, the effects size was modest in the population studied.5 Thus, while re-igniting interest in targeting elements of ‘inflammation’, CANTOS also emphasised that more precise characterisation of disease processes will be essential. This review will consider currently described roles for inflammatory processes in the pathogenesis of atherosclerosis, the use of biomarkers (and their limitations) to characterise these processes and emerging opportunities in the field, including novel therapeutics.
In a current paradigm, atherogenesis is initiated by the deposition and retention of apolipoprotein B-containing lipoproteins into the subintimal space resulting from loss of endothelial integrity, in turn due to disrupted shear stress. Oxidative modification of these lipoproteins in combination with endothelial activation trigger both innate and adaptive immune responses. Following upregulation of a number of cell-adhesion molecules (intercellular adhesion molecule 1, P-selectin and vascular cell adhesion molecule 1 (VCAM-1)), circulating monocytes released from the bone marrow and spleen6 adhere and then …
Contributors NR and RC both devised, wrote and critically revised the manuscript prior to submission.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Commissioned; externally peer reviewed.