Targeting the Immune System in Atherosclerosis: JACC State-of-the-Art Review.

Abstract

Atherosclerosis has long been known as an inflammatory disease. However, whether targeting inflammation improves outcomes was unproven until the recent results of CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study). In this review, we reflect on why it has taken a long time to prove the inflammatory hypothesis of atherosclerosis and derive important lessons for the future. In particular, we discuss the off-target immune-modulatory effects of approved cardiovascular therapies, review the attempted anti-inflammatory therapies including the recently published CIRT (Cardiovascular Inflammation Reduction Trial), and discuss the likely reasons for their failures. We further build on CANTOS to review the immune-modulatory therapies for atherosclerosis currently in trials, and discuss the likelihood of their added value as well as the potential hazard associated with their use. We finally argue for a critical approach to the use of animal models, coupled with the use of humans as model organisms to accelerate the identification of the most appropriate targets.

• Authors: Tian X Zhao, Ziad Mallat
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 73 Issue 13 Pg. 1691-1706 (04 09 2019) ISSN: 1558-3597 [Electronic] United States
• PMID: 30947923 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Immunologic Factors

Topics

• Anti-Inflammatory Agents (therapeutic use)
• Atherosclerosis (drug therapy, immunology)
• Clinical Trials as Topic
• Humans
• Immunologic Factors (therapeutic use)
• Molecular Targeted Therapy