Inflammatory pathways operate at all stages of atherosclerosis. These processes are driven by risk factors and other stimuli that can spark inflammation by eliciting misdirected responses of intrinsic vascular cells and leukocytes, culminating in lesion initiation, progression, and complication. Continuing dissection of the key underlying inflammatory mechanisms with increasingly sophisticated tools has inspired successful clinical trials and enabled translation to the clinic. Here, we review the mechanistic understanding of the etiology and progression of atherosclerosis. We discuss how cardiovascular risk factors converge at the level of the bone marrow to perturb hematopoiesis, yielding output with a pro-inflammatory slant. We further consider how circulating myeloid cells enter, propagate, and persist in atherosclerotic lesions and how intimal macrophages take center stage in regulating the inflammatory milieu. In this context, we delineate emerging therapeutic strategies aimed at mitigating inflammation in atherosclerosis and how these add to existing measures toward reducing the global cardiovascular disease burden.
Libby et al. (Wed,) studied this question.