Century of Milestones and Breakthroughs Related to the Immune Mechanisms of Atherosclerosis.

Abstract

After more than a century of atherosclerosis research, during which the wheel has been re-invented countless times, it is now widely accepted that atherosclerosis is a chronic inflammatory disease of large and medium-sized arteries, initiated in response to the retention and accumulation of apoB-rich lipoproteins in the artery wall. Recent genome-wide association studies (GWAS) as well as large-scale phase 3 randomized clinical trials provided further support for the causal role of cholesterol and inflammation in atherosclerotic cardiovascular disease (ASCVD). While our arsenal of life-saving lipid-lowering therapies has grown considerably over the past decade, most anti-inflammatory drugs failed to make it to the clinic. Therefore, the need for safe and effective anti-inflammatory therapies in patients with, or at risk of, ASCVD remains unmet. Here, we will review major advances in the immune mechanisms of atherosclerosis over the past century (Figure 1), and provide a perspective on future research avenues that could lead to radically new strategies for prevention and treatment.