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Know Diabetes by Heart: A Partnership to Improve Cardiovascular Outcomes in Type 2 Diabetes Mellitus Clinical and genetic characteristics of pulmonary arterial hypertension in Lebanon Lack of Association Between Heart Failure and Incident Cancer Left Main Stenting: What We Have Learnt So Far? Uptake of Drug-Eluting Bioresorbable Vascular Scaffolds in Clinical Practice : An NCDR Registry to Practice Project Cardiac Troponin Composition Characterization after Non ST-Elevation Myocardial Infarction: Relation with Culprit Artery, Ischemic Time Window, and Severity of Injury Myocardial Inflammation Predicts Remodeling and Neuroinflammation After Myocardial Infarction Comparison in prevalence, predictors, and clinical outcome of VSR versus FWR after acute myocardial infarction: The prospective, multicenter registry MOODY trial-heart rupture analysis Impact of Oxidative Stress on the Heart and Vasculature: Part 2 of a 3-Part Series 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

Review ArticleVolume 73, Issue 13, 9 April 2019, Pages 1691-1706

JOURNAL:J Am Coll Cardiol. Article Link

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

TX Zhao, Z Mallat. Keywords: atherosclerosis; clinical trials; immune system; inflammation; therapy and outcome

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-InflammatoryThrombosis 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.