Insights from pre-clinical and clinical studies on the role of innate inflammation in atherosclerosis regression
- 1Cardiology, New York University, United States
Atherosclerosis, the underlying cause of coronary artery (CAD) and other cardiovascular diseases, is initiated by macrophage-mediated immune responses to lipoprotein and cholesterol accumulation in artery walls, which results in the formation of plaques. Unlike at other sites of inflammation, the immune response becomes maladaptive and inflammation fails to resolve. The most common treatment for reducing the risk from atherosclerosis is low density lipoprotein cholesterol (LDL-C) lowering. Studies have shown, however, that while significant lowering of LDL-C reduces the risk of heart attacks to some degree, there is still residual risk for the majority of the population. We and others have observed “residual inflammatory risk” of atherosclerosis after plasma cholesterol lowering in pre-clinical studies, and that this phenomenon is a clinically relevant has been dramatically reinforced by the recent Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) trial.
This review will summarize the role of the innate immune system, specifically macrophages, in atherosclerosis progression and regression, as well as the pre-clinical and clinical models that have provided significant insights into molecular pathways involved in the resolution of plaque inflammation and plaque regression. Partnered with clinical studies that can be envisioned in the post-CANTOS period, including progress in direct plaque therapies, we expect that pre-clinical studies advancing on the path summarized in this review, already revealing key mechanisms, will continue to be essential contributors to achieve the goals of dampening plaque inflammation and inducing its resolution in order to maximize the therapeutic benefits of conventional risk factor modifications, such as LDL-C lowering.
Keywords: innate immunity, Macrophages, Atherosclerosis progression, atherosclerosis regression, pre-clinical models, Clinical Trials as Topic
Received: 16 Dec 2017;
Accepted: 20 Mar 2018.
Edited by:Masanori Aikawa, Harvard Medical School, United States
Reviewed by:Hong Chen, Boston Children's Hospital, Harvard University, United States
Hiroshi Iwata, School of Medicine, Juntendo University, Japan
Copyright: © 2018 Rahman and Fisher. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Edward A. Fisher, New York University, Cardiology, 522 1st Avenue, New York City, 10016, NY, United States, Edward.Fisher@nyumc.org