Targeting inflammation in atherosclerosis — from experimental insights to the clinic - Nature Reviews Drug Discovery

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• clinical studies have now demonstrated unequivocally that modulation of inflammation can forestall the clinical complications of atherosclerosis

• including targeting pivotal inflammatory pathways such as the inflammasomes

• manipulating adaptive immunity

• the ensuing inflammatory response orchestrates the progression and outcome of the disease.

• This study targeted a specific pro-inflammatory cytokine, IL-1β, which has been implicated in atherogenesis through decades of experimental work. CANTOS showed that administration of an anti-IL-1β antibody to patients who were cardiovascularly stable after a myocardial infarction and were being treated according to current guidelines (including with statins) reduced recurrent major adverse cardiovascular events. Subsequent clinical trials with colchicine, another anti-inflammatory agent, have likewise demonstrated clinical benef

• Regular physical activity lowered circulating counts of mononuclear cells as well as their ability to produce pro-inflammatory cytokines232

• also decreases the number of circulating leukocytes

• lammatory processes fuelled by SMCs (part b), macrophages (part c) and neutrophils (part d). b |

• SMCs exposed to modified lipids or pro-inflammatory cytokines then release chemoattractants, including C-C motif chemokine 2 (CCL2) and CCL5 (refs10,11), which promote the recruitment of monocytes12 (Fig. 1a).

• highly inflammatory milieu evokes a healing response

• SMC transition to macrophage-like cells is likely pro-inflammatory and contributes to plaque vulnerability,

• SMCs can also transition to fibroblast cells, which have previously been thought to have the opposite effects.

• This transition depends on the transcription factor TCF21,

• Single-cell RNA sequencing analyses

• genome-wide association

• anti-TNF therapy has not engendered enthusiasm in patients at risk for heart failure, including those with coronary artery disease after ACS.