Heterogeneity Of T Cells In Atherosclerosis Defined By Single Cell Rna Sequencing And Cytometry By Time Of Flight

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

The Vasculome: From Many, One introduces the fundamental bases of the “unity in diversity of the Vasculome, from the coming together of various cell lineages during development, to its deceptively simple solution for architectural design: the efficient interplay of a few types of building blocks supporting key similar functions throughout the body and their highly specialized functional local variations. Specific examples are included to illustrate how the Vasculome is integral to the function and malfunction of different organs, such as the brain or the kidney. Each section is preceded by an introductory summary that will give a high level unified view of the key concepts illustrated in the various chapters in that section. Zorina Galis' The Vasculome was named a finalist in the Clinical Medicine category of the American Association of Publishers’ 2023 PROSE Awards. 2023 PROSE Awards - Winner: Finalist: Clinical Medicine: Association of American Publishers Brings together leading experts who present the latest biomedical thinking about the vasculature from the integrative perspective of the Vasculome Challenges traditional real and perceived boundaries within vascular research areas and stimulates new fundamental thinking and medical explorations Creates the bases for translating the integrative Vasculome concept into improved fundamental and clinical assessment and management of local and systemic contributions of the vasculature in health and disease

Cardiometabolic diseases are driven by both metabolic disorders (obesity, insulin resistance, non-alcoholic fatty liver diseases, and atherosclerosis) and chronic inflammation (e.g. in diabetes, hypertension and autoimmune diseases), leading to coronary artery disease and heart failure. The perivascular or pericardiac adipose tissue expansion affecting both the systemic and tissue compartment is favored in cardiometabolic disease development. This adipose tissue is a major component of the cardiovascular system that is dysregulated during the consumption of fat-enriched diets. Additionally, fat-enriched diets profoundly impact the response of immune cells in specialized tissues, as well as the activation and differentiation of tissue-resident progenitors. This results in both dysfunction and remodeling that is not limited to tissues, but also to cell activity. The fate of cardiovascular diseases associated with metabolic disorders promotes the imbalance in pro- and anti-inflammatory environments.

This textbook focuses on the vascular biology and physiology that underlie vascular disorders in clinical medicine. Vascular biomedicine is a rapidly growing field as new molecular mechanisms of vascular health and disease are unraveled. Many of the major cardiovascular diseases including coronary artery disease, heart failure, stroke and vascular dementia are diseases of the vasculature. In addition vascular injury underpins conditions like kidney failure and cardiovascular complications of diabetes. This field is truly multidisciplinary involving scientists in many domains such as molecular and vascular biology, cardiovascular physiology and pharmacology and immunology and inflammation. Clinically, specialists across multiple disciplines are involved in the management of patients with vascular disorders, including cardiologists, nephrologists, endocrinologists, neurologists and vascular surgeons. This book covers a wide range of topics and provides an overview of the discipline of vascular biomedicine without aiming at in-depth reviews, but rather offering up-to-date knowledge organized in concise and structured chapters, with key points and pertinent references. The structure of the content provides an integrative and translational approach from basic science (e.g. stem cells) to clinical medicine (e.g. cardiovascular disease). The content of this book is targeted to those who are new in the field of vascular biology and vascular medicine and is ideal for medical students, graduate and postgraduate students, clinical fellows and academic clinicians with an interest in the vascular biology and physiology of cardiovascular disease and related pathologies.

Single-cell OMICs analyses have recently become one of the most promising tools to probe biology at the cellular level, in large part due to its ability to address issues beyond the bulk analysis – a window into cellular heterogeneity. The ability to profile transcriptomic, epigenomic, proteomics, and metabolomics at the single cell level including more recently the spatial information has enhanced our ability to understand interactions between biomolecules in different contexts leading to the discovery of specific cellular subpopulations as well as biological mechanisms underlying pathologies which may be amenable to therapeutic interventions. The scale and availability of a variety of technologies to measure intricate molecular details have provided an impetus to research in many disease areas, including cardiovascular medicine.

Macrophages are core components of the innate immune system. Once activated, they may have either pro- or anti-inflammatory effects that include pathogen killing, safe disposal of apoptotic cells or tissue renewal. The activation state of macrophages is conceptualized by the so-called M1/M2 model of polarization. M2 macrophages are not simply antagonists of M1 macrophages; rather, they represent a network of tissue resident macrophages with roles in tissue development and organ homeostasis. M2 macrophages govern functions at the interfaces of immunity, tissue development and turnover, metabolism, and endocrine signaling. Dysfunction in M2 macrophages can ruin the healthy interplay between the immune system and metabolic processes, and lead to diseases such as insulin resistance, metabolic syndrome, and type 1 and 2 diabetes mellitus. Furthermore, M2 macrophages are essential for healthy tissue development and immunological self-tolerance. Worryingly, these functions of M2 macrophages can also be disrupted, resulting in tumor growth and autoimmunity. This book comprehensively discusses the biology of M2 macrophages, summarizes the current state of knowledge, and highlights key questions that remain unanswered.