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Inflammation in coronary artery disease and acute myocardial infarction - is the stage set for novel therapies?


Klingenberg, Roland; Luscher, Thomas F (2012). Inflammation in coronary artery disease and acute myocardial infarction - is the stage set for novel therapies? Current Pharmaceutical Design, 18(28):4358-4369.

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.

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.

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16 citations in Web of Science®
20 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2012
Deposited On:28 Feb 2013 12:20
Last Modified:05 Apr 2016 16:34
Publisher:Bentham Science Publishers
ISSN:1381-6128
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.2174/138161212802481219
PubMed ID:22390645
Permanent URL: https://doi.org/10.5167/uzh-74615

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