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Cytokines as therapeutic targets for cardio- and cerebrovascular diseases


Liberale, Luca; Ministrini, Stefano; Carbone, Federico; Camici, Giovanni G; Montecucco, Fabrizio (2021). Cytokines as therapeutic targets for cardio- and cerebrovascular diseases. Basic Research in Cardiology, 116:23.

Abstract

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.

Abstract

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.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Center for Molecular Cardiology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Physiology
Health Sciences > Cardiology and Cardiovascular Medicine
Health Sciences > Physiology (medical)
Uncontrolled Keywords:Physiology (medical), Cardiology and Cardiovascular Medicine, Physiology
Language:English
Date:1 December 2021
Deposited On:12 Oct 2022 13:18
Last Modified:02 Nov 2022 01:52
Publisher:Springer
ISSN:0300-8428
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1007/s00395-021-00863-x
PubMed ID:33770265
Project Information:
  • : FunderRete Cardiologica of the Italian Ministry of Health
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  • : FunderSNSF
  • : Grant ID310030_197510
  • : Project TitleInflamm-aging: a novel therapeutic concept for age-dependent vascular dysfunction and its implications for stroke
  • : FunderAlfred and Annemarie von Sick Grants for Translational and Clinical Research Cardiology and Oncology
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  • : FunderSchweizerische Herzstiftung
  • : Grant ID
  • : Project Title
  • : FunderSheikh Khalifa's Foundation
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  • : Project Title
  • : FunderUniversität Zürich
  • : Grant ID
  • : Project Title
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)