Title:Inflammation in Coronary Artery Disease and Acute Myocardial Infarction - is the Stage Set for Novel Therapies?
Volume: 18
Issue: 28
Author(s): Roland Klingenberg and Thomas F. Luscher
Affiliation:
Keywords:
Coronary artery disease, myocardial infarction, atherosclerosis, inflammation, immune system, drugs, pharmaceutics, pharmaceutics, Acute myocardial infarction (AMI), interleukin-1, tumor necrosis factor-α
Abstract: Acute myocardial infarction (AMI) constitutes the major cause of death in most nations and death rates and morbidity remain
substantial in the years thereafter. Inflammation is a hallmark throughout the distinct stages of atherosclerotic lesion formation preceding
AMI as well as at the time of plaque rupture and during the post-infarct repair phase. Epidemiological, genetic, clinical and experimental
evidence converges on inflammation as a pivotal factor in disease progression and exacerbation. Harnessing its harmful consequences
constitutes an attractive therapeutic approach to address this unmet medical need. Components of the innate and adaptive immune system
with the characteristic cytokines interleukin-1 and tumor necrosis factor-α, respectively exert prominent functions in atherogenesis and
post-infarct remodeling. Leukocyte subsets of the monocyte/macrophage and CD4+ T lymphocyte cell lineage interacting with a vast array
of cells comprising platelets, neutrophils, dendritic cells, mast cells, vascular smooth muscle cells and fibroblasts orchestrate the inflammatory
pathophysiology underlying plaque progression in the vasculature and fibrotic repair of the infarct. This pathophysiology is
amenable to modification by drugs targeting cell proliferation, cell migration, osteogenic/fibrous turnover of the extracellular matrix
ranging from antimetabolites, glucocorticoids, specific cytokine and leukotriene antagonists to classic immunosuppressive agents and
vaccines directed specifically at certain disease-relevant antigens. Based on published data on clinical safety and clinical/experimental efficacy
in inhibiting disease progression this review covers recent advances in this field and aims to propose candidate drugs for future
clinical trials.
