Atherosclerosis is the most common pathological mechanism underlying coronary artery disease (CAD), encompassing both acute coronary syndromes (ACS) and chronic coronary syndromes (CCS). Traditionally, the plaque formation process has been perceived as a consequence of cholesterol accumulation (particularly scavenger receptor-mediated uptake of modified low-density lipoprotein), leading to continuous plaque growth. Subendothelial intimal layer build-up further leads to progressive stenosis, reduced blood flow, and, eventually, tissue hypoxia. In addition, spontaneous thrombotic vessel occlusion and embolic events may constitute the common pathophysiological pathway for acute major cardiovascular events, namely myocardial infarction (MI) and stroke.

Although John Hunter first pioneered the inflammatory theory in 1794, it was not until 1994 that worse outcomes in patients with ACS were linked to higher C-reactive protein (CRP) levels, and it was proposed that plaque inflammation could be responsible for plaque fissuring. Hence, inflammation was finally linked to atherosclerosis and thrombosis. Moreover, it was later demonstrated that interleukin (IL) 1β, a pro-inflammatory cytokine, facilitates hematopoietic progenitor cell proliferation through glucose and cholesterol metabolism, thus promoting neutrophil extracellular trap formation in the growing plaque. Indeed, MI is accompanied by neutrophil infiltration, which is paramount to inflammation regulation.

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