TY - JOUR
T1 - Cytokines as therapeutic targets for cardio- and cerebrovascular diseases
AU - Liberale, Luca
AU - Ministrini, Stefano
AU - Carbone, Federico
AU - Camici, Giovanni G.
AU - Montecucco, Fabrizio
N1 - Funding Information:
Open Access funding provided by Universität Zürich. This work has been supported by a grant from the Rete Cardiologica of the Italian Ministry of Health to FM. Furthermore, the present work was supported by the Swiss National Science Foundation (to GGC [310030_197510]), the Alfred and Annemarie von Sick Grants for Translational and Clinical Research Cardiology and Oncology to GGC, the Swiss Heart Foundation to GGC and LL, and the Foundation for Cardiovascular Research–Zurich Heart House. GGC is the recipient of a Sheikh Khalifa's Foundation Assistant Professorship at the Faculty of Medicine, University of Zurich.
Publisher Copyright:
© 2021, The Author(s).
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/12
Y1 - 2021/12
N2 - Despite major advances in prevention and treatment, cardiac and cerebral atherothrombotic complications still account for substantial morbidity and mortality worldwide. In this context, inflammation is involved in the chronic process leading atherosclerotic plaque formation and its complications, as well as in the maladaptive response to acute ischemic events. For this reason, modulation of inflammation is nowadays seen as a promising therapeutic strategy to counteract the burden of cardio- and cerebrovascular disease. Being produced and recognized by both inflammatory and vascular cells, the complex network of cytokines holds key functions in the crosstalk of these two systems and orchestrates the progression of atherothrombosis. By binding to membrane receptors, these soluble mediators trigger specific intracellular signaling pathways eventually leading to the activation of transcription factors and a deep modulation of cell function. Both stimulatory and inhibitory cytokines have been described and progressively reported as markers of disease or interesting therapeutic targets in the cardiovascular field. Nevertheless, cytokine inhibition is burdened by harmful side effects that will most likely prevent its chronic use in favor of acute administrations in well-selected subjects at high risk. Here, we summarize the current state of knowledge regarding the modulatory role of cytokines on atherosclerosis, myocardial infarction, and stroke. Then, we discuss evidence from clinical trials specifically targeting cytokines and the potential implication of these advances into daily clinical practice.
AB - Despite major advances in prevention and treatment, cardiac and cerebral atherothrombotic complications still account for substantial morbidity and mortality worldwide. In this context, inflammation is involved in the chronic process leading atherosclerotic plaque formation and its complications, as well as in the maladaptive response to acute ischemic events. For this reason, modulation of inflammation is nowadays seen as a promising therapeutic strategy to counteract the burden of cardio- and cerebrovascular disease. Being produced and recognized by both inflammatory and vascular cells, the complex network of cytokines holds key functions in the crosstalk of these two systems and orchestrates the progression of atherothrombosis. By binding to membrane receptors, these soluble mediators trigger specific intracellular signaling pathways eventually leading to the activation of transcription factors and a deep modulation of cell function. Both stimulatory and inhibitory cytokines have been described and progressively reported as markers of disease or interesting therapeutic targets in the cardiovascular field. Nevertheless, cytokine inhibition is burdened by harmful side effects that will most likely prevent its chronic use in favor of acute administrations in well-selected subjects at high risk. Here, we summarize the current state of knowledge regarding the modulatory role of cytokines on atherosclerosis, myocardial infarction, and stroke. Then, we discuss evidence from clinical trials specifically targeting cytokines and the potential implication of these advances into daily clinical practice.
KW - Cardiovascular disease
KW - Cerebrovascular disease
KW - Cytokines
KW - IL-1
KW - IL-6
KW - Interleukins
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U2 - 10.1007/s00395-021-00863-x
DO - 10.1007/s00395-021-00863-x
M3 - Review article
AN - SCOPUS:85103345336
VL - 116
JO - Basic Research in Cardiology
JF - Basic Research in Cardiology
SN - 0300-8428
IS - 1
M1 - 23
ER -