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Vol. 72. Issue 9.
Pages 760-766 (September 2019)
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Vol. 72. Issue 9.
Pages 760-766 (September 2019)
Focus on: Inflammatory State and Cardiovascular Risk Control: Towards a New Paradigm (I)
DOI: 10.1016/j.rec.2019.03.006
Potential Therapeutic Value of Interleukin 1b-targeted Strategies in Atherosclerotic Cardiovascular Disease
Valor terapéutico potencial de las estrategias dirigidas contra la interleucina 1β en la enfermedad cardiovascular ateroesclerótica
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Vanesa Viana-Huete, José J. Fuster
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jjfuster@cnic.es

Corresponding author: Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029, Madrid, Spain.
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
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Rev Esp Cardiol. 2019;72:767-7310.1016/j.rec.2019.03.007
Sergio Martínez-Hervás, Herminia González-Navarro
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Abstract

Clinical trials have unequivocally shown that cholesterol-lowering drugs decrease the risk of atherosclerotic cardiovascular disease in an exceptionally wide range of individuals. Yet, even when treated optimally according to current standards, many individuals still experience life-threatening ischemic events. Emerging experimental and clinical evidence strongly suggests that persistent inflammation is a major driver of this residual risk, which has opened the door to the application of anti-inflammatory drugs for cardiovascular disease prevention. Here, we review our current knowledge of the biology of interleukin-1β, a key regulator of inflammation in atherosclerotic plaque and the target of the first clinical trial to demonstrate that an anti-inflammatory drug can effectively reduce cardiovascular risk. We discuss the challenges faced by interleukin-1β inhibitors and other anti-inflammatory compounds in their translation to the clinical scenario, and identify other potential targets within this signaling pathway that hold promise in the cardiovascular setting.

Keywords:
Interleukin-1β
CANTOS
Canakinumab
NLRP3 inflammasome
Clonal hematopoiesis
Abbreviations:
CVD
hsCRP
IL-1β
MI
Resumen

Múltiples ensayos clínicos han demostrado de forma inequívoca que los medicamentos hipocolesterolemiantes disminuyen el riesgo de enfermedad cardiovascular ateroesclerótica de una muy amplia variedad de personas. A pesar de esto, muchas personas tratadas de manera óptima según los estándares actuales presentan eventos isquémicos potencialmente letales. Evidencia experimental y clínica reciente indica que la inflamación persistente en la placa ateroesclerótica es uno de los principales mecanismos subyacentes a este riesgo residual, lo que ha abierto la puerta a la aplicación de fármacos antiinflamatorios para la prevención de la enfermedad cardiovascular. En este artículo se repasa el conocimiento actual sobre la biología de la citocina interleucina 1β, un regulador clave de la respuesta inflamatoria en la placa ateroesclerótica y la diana del primer ensayo clínico que ha demostrado que un fármaco antiinflamatorio puede reducir de forma efectiva el riesgo cardiovascular. Se discuten los importantes retos a los que se enfrentan los inhibidores de la interleucina 1β y otros compuestos antiinflamatorios en su traslación al ámbito clínico y se identifican otras posibles dianas en esta vía de señalización, prometedoras en el contexto cardiovascular.

Palabras clave:
Interleucina 1β
CANTOS
Canakinumab
Inflamasoma NLRP3
Hematopoyesis clonal

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