Inflammation and Cardiac Diseases
http://www.100md.com
《新英格兰医药杂志》
Our views of atherogenesis have evolved dramatically during the past several decades. The cholesterol hypothesis of the 1950s and 1960s led to the theory of endothelial injury in the 1970s and 1980s, which, in turn, developed into the concept that atherosclerosis is an inflammatory disease. These theories are not exclusive but, rather, complementary. For example, cholesterol, endothelial injury, and inflammation all play a role in atherogenesis: oxidized low-density lipoprotein triggers endothelial cells to stimulate the migration and activation of leukocytes within the vessel wall, which leads to an inflammatory response.
(Figure)
Inflammatory Cells in a Carotid Atheroma.
Courtesy of Galina K. Sukhova and Peter Libby.
In their excellent book, Inflammation and Cardiac Diseases, Feuerstein, Libby, and Mann focus first on vascular inflammation. Half of all patients who have myocardial infarctions have normal plasma lipid levels. Numerous clinical studies involving such patients have identified a set of inflammatory biologic markers that predict the risk of cardiovascular events. Many of these markers — interleukin-6, fibrinogen, and C-reactive protein, to name a few — are components of the acute-phase response, an innate, systemic inflammatory reaction. Why is an acute immune response chronically activated in patients with atherosclerosis? What is the role of acute-phase reactants in heart disease? Masterly chapters on interleukin-6 and C-reactive protein answer these questions.
The editors then turn their attention to inflammation in the myocardium during ischemia, reperfusion, and heart failure. Our understanding of the pathogenesis of heart failure has evolved from hypervolemic models to hemodynamic and then neurohormonal ones. Basic-science and clinical researchers have discovered that inflammation and myocardial remodeling play a critical role in heart failure. Innate immunity is activated when neutrophils and monocytes migrate into the injured myocardium, damaging myocytes by releasing innate immune effectors such as complement and radicals, and stimulating inflammation by secreting proinflammatory cytokines, including interferon-, tumor necrosis factor (TNF-), and chemokines. In clearly focused sections of the book, the authors explore the roles of each of these innate immune signals in cardiac disease.
Mann tells a fascinating story in his chapter on cytokines that illustrates the importance of understanding the nuances of specific inflammatory pathways in heart disease. TNF- levels are elevated in patients with ischemic or idiopathic dilated cardiomyopathy. Early preclinical and clinical studies suggested that interfering with TNF- synthesis was beneficial. However, two large, randomized clinical trials failed to show any benefit to using selective TNF- antagonists. In fact, patients receiving anti–TNF- drugs had a slightly increased risk of death or hospitalization. Clearly, key aspects of inflammation in cardiac disease are still not understood.
Our knowledge of this subject is still evolving. Inflammation and Cardiac Diseases is an excellent summary of the ways in which innate immune pathways are activated in diseases of the heart. The book challenges us to identify the triggers of such immunity, to explore the role of innate immune signaling in cardiac disease, and to develop new types of immunomodulatory therapies.
Charles J. Lowenstein, M.D.
Johns Hopkins University School of Medicine
Baltimore, MD 21205
clowenst@jhmi.edu((Progress in Inflammation)
(Figure)
Inflammatory Cells in a Carotid Atheroma.
Courtesy of Galina K. Sukhova and Peter Libby.
In their excellent book, Inflammation and Cardiac Diseases, Feuerstein, Libby, and Mann focus first on vascular inflammation. Half of all patients who have myocardial infarctions have normal plasma lipid levels. Numerous clinical studies involving such patients have identified a set of inflammatory biologic markers that predict the risk of cardiovascular events. Many of these markers — interleukin-6, fibrinogen, and C-reactive protein, to name a few — are components of the acute-phase response, an innate, systemic inflammatory reaction. Why is an acute immune response chronically activated in patients with atherosclerosis? What is the role of acute-phase reactants in heart disease? Masterly chapters on interleukin-6 and C-reactive protein answer these questions.
The editors then turn their attention to inflammation in the myocardium during ischemia, reperfusion, and heart failure. Our understanding of the pathogenesis of heart failure has evolved from hypervolemic models to hemodynamic and then neurohormonal ones. Basic-science and clinical researchers have discovered that inflammation and myocardial remodeling play a critical role in heart failure. Innate immunity is activated when neutrophils and monocytes migrate into the injured myocardium, damaging myocytes by releasing innate immune effectors such as complement and radicals, and stimulating inflammation by secreting proinflammatory cytokines, including interferon-, tumor necrosis factor (TNF-), and chemokines. In clearly focused sections of the book, the authors explore the roles of each of these innate immune signals in cardiac disease.
Mann tells a fascinating story in his chapter on cytokines that illustrates the importance of understanding the nuances of specific inflammatory pathways in heart disease. TNF- levels are elevated in patients with ischemic or idiopathic dilated cardiomyopathy. Early preclinical and clinical studies suggested that interfering with TNF- synthesis was beneficial. However, two large, randomized clinical trials failed to show any benefit to using selective TNF- antagonists. In fact, patients receiving anti–TNF- drugs had a slightly increased risk of death or hospitalization. Clearly, key aspects of inflammation in cardiac disease are still not understood.
Our knowledge of this subject is still evolving. Inflammation and Cardiac Diseases is an excellent summary of the ways in which innate immune pathways are activated in diseases of the heart. The book challenges us to identify the triggers of such immunity, to explore the role of innate immune signaling in cardiac disease, and to develop new types of immunomodulatory therapies.
Charles J. Lowenstein, M.D.
Johns Hopkins University School of Medicine
Baltimore, MD 21205
clowenst@jhmi.edu((Progress in Inflammation)