The Present and Future
JACC Review Topic of the Week
Inflammation, Immunity, and Infection in Atherothrombosis: JACC Review Topic of the Week

https://doi.org/10.1016/j.jacc.2018.08.1043Get rights and content
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Abstract

Observations on human and experimental atherosclerosis, biomarker studies, and now a large-scale clinical trial support the operation of immune and inflammatory pathways in this disease. The factors that incite innate and adaptive immune responses implicated in atherogenesis and in lesion complication include traditional risk factors such as protein and lipid components of native and modified low-density lipoprotein, angiotensin II, smoking, visceral adipose tissue, and dysmetabolism. Infectious processes and products of the endogenous microbiome might also modulate atherosclerosis and its complications either directly, or indirectly by eliciting local and systemic responses that potentiate disease expression. Trials with antibiotics have not reduced recurrent cardiovascular events, nor have vaccination strategies yet achieved clinical translation. However, anti-inflammatory interventions such as anticytokine therapy and colchicine have begun to show efficacy in this regard. Thus, inflammatory and immune mechanisms can link traditional and emerging risk factors to atherosclerosis, and offer novel avenues for therapeutic intervention.

Key Words

basic & translational research

Abbreviations and Acronyms

hsCRP
high-sensitivity C-reactive protein
IL
interleukin
LDL
low-density lipoprotein
PAMP
pathogen-associated molecular pattern
Th
helper T-cell subtype
TLR
toll-like receptor

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Dr. Libby was supported by grants from the National Heart, Lung, and Blood Institute (NHLBI) (HL080472) and the RRM Charitable Fund. Dr. Loscalzo was supported by National Institutes of Health (NIH) grants HL119145, HG007690, GM107618, and HL061795, and the American Heart Association grant Scaling the Computation of Predicting Drug Protein Interactions. Dr. Farkouh has received NIHLBI grant support (U01HL28606). Dr. Hsue has received grant support from the National Institute of Allergy and Infectious Diseases (K24AI112393) and the NIH (R01HL125034). Dr. Amar has received grant support from the NHLBI (R01HL076801) and the NIH (R01DE014079). Dr. Libby’s laboratory has received funding from Novartis; he is an unpaid consultant to Amgen, AstraZeneca, Esperion Therapeutics, Ionis Pharmaceuticals, Sanofi-Regeneron, and XBiotech, Inc.; and a member of the scientific advisory board for Corvidia Therapeutics, Olatec Therapeutics, and MedImmune. Dr. Ridker has received research grant support from Novartis, Kowa, Pfizer, and the NHLBI; has served as a consultant for Novartis, Corvidia, Inflazome, and Pfizer; and is listed as a co-inventor on patents held by the Brigham and Women’s Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease and diabetes that have been licensed to AstraZeneca and Seimens. Dr. Farkouh has received research support from Amgen. Dr. Hsue has received grant support from Pfizer; and has received honoraria from Gilead. Dr. Hasan works for the NHLBI/NIH, but any opinions, findings, and conclusions expressed in this review are those of the author and do not reflect the views of the NHLBI or the NIH. Dr. Fuster has reported that he has no relationships relevant to the contents of this paper to disclose.

Listen to this manuscript's audio summary by JACC Editor-in-Chief Dr. Valentin Fuster.