Atherosclerosis And Autoimmunity

Presenting further studies in the prevention and treatment of coronary artery disease, this book brings together the knowledge accrued in the past decade concerning the role of immunity in the initiation and perpetuation of atherosclerosis. A strong group of international contributors summarize the diverse aspects of the interrelationship between the immune system and atherosclerosis.

This first volume represents the state-of-the-art in the field of cardiovascular disease and autoimmune rheumatic diseases. Systemic autoimmune diseases comprise a family of conditions that share common pathogenetic mechanisms as well as a multi-organ involvement including the heart. This volume has been subdivided into three parts. In the first part, the immune mechanisms involved in cardiac damage have been considered. The role of proinflammatory and regulatory cytokines in driving an autoimmune response to cardiac self-tissues has been analysed. Moreover, the prevalence, the clinical meaning and the hypothetical pathogenicity of a broad spectrum of organ and non-organ specific autoantibodies have been discussed in detail. In the second part of the volume, the role of humoral and innate immunity in promoting the development of atherosclerotic plaque has been extensively reviewed, along with the newly discovered anti-inflammatory properties of statins. These two parts of the volume deal with exciting aspects of this topic, suggesting a very close connection between heart diseases and immunology. Finally, in the third part, the cardiac manifestations observed in the major systemic autoimmune conditions have been comprehensively examined. This book yields an impressive body of well ordered information, highlighting key references and summarising the experience of a selected panel of distinguished physician-scientists actively involved in the field of cardiovascular disease and systemic autoimmunity.

Plasticity and dynamism characterize the immune system as a tissue-integrating network with defensive functions. Blood and lymphatic vessel trees constitute the most evident and intuitive physical platform for the development of the net of interactions between immune cells, body tissues and foreign agents. Moreover vessel repair and immune patrolling are intimately linked physiological functions with common evolutionary roots. Not surprisingly variable degrees of vascular inflammation are often detectable in the setting of systemic inflammation and autoimmunity, whereas research in the field of cardiovascular pathology is progressively converging towards the identification of a common inflammatory background. The definition of the role of vascular inflammation in causing, sustaining and/or predicting the development of systemic autoimmunity constitute a challenging, unexplored frontier towards the development of a new generation of treatments and a better patient care.

The prevalence of autoimmune diseases and rheumatic conditions is constantly increasing. Autoimmune diseases affect approximately 7-10% of the population of the United States, while more than 50,000,000 American adults suffer from some type of arthritis. The Heart in Rheumatic, Autoimmune and Inflammatory Diseases examines the complex mechanisms relating to cardiac diseases from a pathophysiological and clinical point of view. Autoimmune rheumatic diseases can affect the coronary vessels, myocardium, pericardium, heart valves and the conduction system. The diagnosis of these unique cardiac complications necessitates medical awareness and a high index of suspicion. Increased risk of advanced atherosclerosis plays a pivotal role in the development of cardiac diseases in systemic, rheumatic and autoimmune illnesses. Yet, other complex immune medicated mechanisms may contribute to the pathogenesis. Patients' optimal care requires coordination between the primary caregiver, the rheumatologist, immunologist and cardiologist. Screening for cardiovascular risk factors, recognition of high-risk patients and identification of subclinical cardiac conditions are of great importance. Moreover, regulation of inflammation, as well as abnormal immune responses and the initiation of early treatments should be the focus of patient management. A continuous attempt to identify novel therapeutic targets and change the natural history of the underlying disease and its cardiac manifestations is in progress. The book aims at providing the readers with a state of the art collection of up to date information regarding clinically important topics based on experts' perspectives. This book was a result of an extended coordinated collaboration of one-hundred and fifty-four distinguished scientists from thirty-one countries around the globe. A review of common, as well as unusual (yet clinically significant) medical cardiac complications of prevalent rheumatic, autoimmune and inflammatory diseases. Focuses on aspects of pathophysiological processes, clinical presentations, screening tests, prognostic implications and novel therapeutic approaches. Presents an up-to-date “level of evidence and “strengths of recommendations for suggested therapies and reviews all randomized clinical trials, meta-analyses and other supporting published clinical findings.

Abstract: The infiltration and accumulation of pro- and anti-inflammatory leukocytes within the intimal layer of the arterial wall is a hallmark of developing and progressing atherosclerosis. While traditionally perceived as macrophage- and foam cell-dominated disease, it is now established that atherosclerosis is a partial autoimmune disease that involves the recognition of peptides from ApoB (apolipoprotein B), the core protein of LDL (low-density lipoprotein) cholesterol particles, by CD4+ T-helper cells and autoantibodies against LDL and ApoB. Autoimmunity in the atherosclerotic plaque has long been understood as a pathogenic T-helper type-1 driven response with proinflammatory cytokine secretion. Recent developments in high-parametric cell immunophenotyping by mass cytometry, single-cell RNA-sequencing, and in tools exploring antigen-specificity have established the existence of several unforeseen layers of T-cell diversity with mixed TH1 and T regulatory cells transcriptional programs and unpredicted fates. These findings suggest that pathogenic ApoB-reactive T cells evolve from atheroprotective and immunosuppressive CD4+ T regulatory cells that lose their protective properties over time. Here, we discuss T-cell heterogeneity in atherosclerosis with a focus on plasticity, antigen-specificity, exhaustion, maturation, tissue residency, and its potential use in clinical prediction