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血流动力学与动脉粥样硬化

Abstract

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Role of local coronary blood flow patterns and shear stress on the development of microvascular and epicardial endothelial dysfunction and coronary plaque Endothelial ACKR3 drives atherosclerosis by promoting immune cell adhesion to vascular endothelium Low‑Shear Stress Promotes Atherosclerosis via Inducing Endothelial Cell Pyroptosis Mediated by IKKε/STAT1/NLRP3 Pathway Disturbed shear stress promotes atherosclerosis through TRIM21-regulated MAPK6 degradation and consequent endothelial inflammation
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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.