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Paul M. Ridker, Manas A. Rane
IL (interleukin)-6 is a pivotal cytokine of innate immunity, which enacts a broad set of physiological functions traditionally associated with host defense, immune cell regulation, proliferation, and differentiation. Following recognition of innate immune pathways leading from the NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome to IL-1 to IL-6 and on to the hepatically derived clinical biomarker CRP (C-reactive protein), an expanding literature has led to understanding of the proatherogenic role for IL-6 in cardiovascular disease and thus the potential for IL-6 inhibition as a novel method for vascular protection. In this review, we provide an overview of the mechanisms by which IL-6 signaling occurs and how that impacts upon pharmacological inhibition; describe murine models of IL-6 and atherogenesis; summarize human epidemiological data outlining the utility of IL-6 as a biomarker of vascular risk; outline genetic data suggesting a causal role for IL-6 in systemic atherothrombosis and aneurysm formation; and then detail the potential role of IL-6 inhibition in stable coronary disease, acute coronary syndromes, heart failure, and the atherothrombotic complications associated with chronic kidney disease and end-stage renal failure. Finally, we review anti-inflammatory and antithrombotic findings for ziltivekimab, a novel IL-6 ligand inhibitor being developed specifically for use in atherosclerotic disease and poised to be tested formally in a large-scale cardiovascular outcomes trial focused on individuals with chronic kidney disease and elevated levels of CRP, a population at high residual atherothrombotic risk, high residual inflammatory risk, and considerable unmet clinical need.
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Ridker, P. M., & Rane, M. A. (2021). Interleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease. Circulation Research, 128(11), 1728–1746. https://doi.org/10.1161/circresaha.121.319077
Ridker, Paul M., and Manas A. Rane. "Interleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease." Circulation Research, vol. 128, no. 11, 2021, pp. 1728–1746, https://doi.org/10.1161/circresaha.121.319077.
Ridker, Paul M., and Manas A. Rane. "Interleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease." Circulation Research 128, no. 11 (2021): 1728–1746. https://doi.org/10.1161/circresaha.121.319077.
Ridker P. M., Rane M. A. Interleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease // Circulation Research. — 2021. — Vol. 128, № 11. — P. 1728–1746. — URL: https://doi.org/10.1161/circresaha.121.319077
@article{ridker2021interleukin,
title = {{Interleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease}},
author = {Paul M. Ridker and Manas A. Rane},
journal = {Circulation Research},
year = {2021},
volume = {128},
number = {11},
pages = {1728--1746},
doi = {10.1161/circresaha.121.319077},
url = {https://doi.org/10.1161/circresaha.121.319077}
}TY - JOUR AU - Ridker, Paul M. AU - Rane, Manas A. TI - Interleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease JO - Circulation Research VL - 128 IS - 11 SP - 1728 EP - 1746 PY - 2021 DA - 2021/05/17 DO - 10.1161/circresaha.121.319077 UR - https://doi.org/10.1161/circresaha.121.319077 ER -
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