Back
Full-text
Journal article

Anti-inflammatory therapies for cardiovascular disease.

  • Ridker PM Division of Cardiovascular Medicine, Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue, Boston, MA, 02215 USA Division of Preventive Medicine, Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue, Boston, MA, 02215 USA pridker@partners.org.
  • Lüscher TF Cardiology, University Heart Center, University Hospital Zurich and Center for Molecular Cardiology, Campus Schlieren, University Zurich, Zurich, Switzerland.
  • 2014-05-28
Published in:
  • European heart journal. - 2014
Atherosclerosis
C reactive protein
Canakinumab
Colchicine
Darapladib
Inflammasome
Inflammation
Interleukin-6
Methotrexate
Salsalate
Adaptive Immunity
Anti-Inflammatory Agents
Antioxidants
Atherosclerosis
C-Reactive Protein
Carrier Proteins
Cell Adhesion Molecules
Colchicine
Humans
Hydroxychloroquine
Interleukin-1
Interleukin-6
Leukotriene Antagonists
Lipoproteins, HDL
Methotrexate
NLR Family, Pyrin Domain-Containing 3 Protein
Phospholipase A2 Inhibitors
Receptors, Interleukin-1
Serpins
Signal Transduction
Sirtuins
Thrombosis
Tumor Necrosis Factor-alpha
Vaccination
English Atherothrombosis is no longer considered solely a disorder of lipoprotein accumulation in the arterial wall. Rather, the initiation and progression of atherosclerotic lesions is currently understood to have major inflammatory influences that encompass components of both the innate and acquired immune systems. Promising clinical data for 'upstream' biomarkers of inflammation such as interleukin-6 (IL-6) as well as 'downstream' biomarkers such as C-reactive protein, observations regarding cholesterol crystals as an activator of the IL-1β generating inflammasome, and recent Mendelian randomization data for the IL-6 receptor support the hypothesis that inflammatory mediators of atherosclerosis may converge on the central IL-1, tumour necrosis factor (TNF-α), IL-6 signalling pathway. On this basis, emerging anti-inflammatory approaches to vascular protection can be categorized into two broad groups, those that target the central IL-6 inflammatory signalling pathway and those that do not. Large-scale Phase III trials are now underway with agents that lead to marked reductions in IL-6 and C-reactive protein (such as canakinumab and methotrexate) as well as with agents that impact on diverse non-IL-6-dependent pathways (such as varespladib and darapladib). Both approaches have the potential to benefit patients and reduce vascular events. However, care should be taken when interpreting these trials as outcomes for agents that target IL-6 signalling are unlikely to be informative for therapies that target alternative pathways, and vice versa. As the inflammatory system is redundant, compensatory, and crucial for survival, evaluation of risks as well as benefits must drive the development of agents in this class.
Language
  • English
Open access status
green
Identifiers
Persistent URL
https://sonar.ch/global/documents/141583
Statistics
Document views: 14 File downloads:
  • fulltext.pdf: 0