Cardiovascular diseases claim more lives worldwide than any other. Etiologically, the dominant trajectory involves atherosclerosis, a chronic inflammatory process of lipid-rich lesion growth in the ...vascular wall that can cause life-threatening myocardial infarction (MI). Those who survive MI can develop congestive heart failure, a chronic condition of inadequate pump activity that is frequently fatal. Leukocytes (white blood cells) are important participants at the various stages of cardiovascular disease progression and complication. This Review will discuss leukocyte function in atherosclerosis, MI, and heart failure.
Cytokine storm and sepsis disease pathogenesis Chousterman, Benjamin G.; Swirski, Filip K.; Weber, Georg F.
Seminars in immunopathology,
07/2017, Letnik:
39, Številka:
5
Journal Article
Recenzirano
Infectious diseases are a leading cause of death worldwide. Sepsis is a severe clinical syndrome related to the host response to infection. The severity of infections is due to an activation cascade ...that will lead to an autoamplifying cytokine production: the cytokine storm. Cytokines are a broad category of relatively small proteins (<40 kDa) that are produced and released with the aim of cell signaling. Our understanding of the processes that trigger this tremendous amount of cytokine production has made dramatic progress over the last decades, but unfortunately, these findings could not translate yet into effective treatments; so far, all clinical trials targeting cytokine production or effects failed. This review aims to summarize the pathophysiology of the cytokine storm; to describe the type, effects, and kinetics of cytokine production; and to discuss the therapeutic challenges of targeting cytokines. New promising therapeutic strategies focusing on the endothelium, as a source and a target of cytokines, are described.
Physicians have traditionally viewed ischemic heart disease in a cardiocentric manner: plaques grow in arteries until they block blood flow, causing acute coronary and other ischemic syndromes. ...Recent research provides new insight into the integrative biology of inflammation as it contributes to ischemic cardiovascular disease. These results have revealed hitherto unsuspected inflammatory signaling networks at work in these disorders that link the brain, autonomic nervous system, bone marrow, and spleen to the atherosclerotic plaque and to the infarcting myocardium. A burgeoning clinical published data indicates that such inflammatory networks-far from a mere laboratory curiosity-operate in our patients and can influence aspects of ischemic cardiovascular disease that determine decisively clinical outcomes. These new findings enlarge the circle of the traditional "cardiovascular continuum" beyond the heart and vessels to include the nervous system, the spleen, and the bone marrow.
Monocyte and Macrophage Heterogeneity in the Heart Nahrendorf, Matthias; Swirski, Filip K
Circulation research,
2013-June-7, 2013-Jun-07, 2013-06-07, 20130607, Letnik:
112, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Monocytes and macrophages are innate immune cells that reside and accumulate in the healthy and injured heart. The cells and their subsets pursue distinct functions in steady-state and disease, and ...their tenure may range between hours and months. Some subsets are highly inflammatory, whereas others support tissue repair. This review discusses current concepts of lineage relationships and crosstalk of systems, highlights open questions, and describes tools for studying monocyte and macrophage subsets in the murine and human heart.
Hematopoiesis and Cardiovascular Disease Poller, Wolfram C; Nahrendorf, Matthias; Swirski, Filip K
Circulation research,
2020-April-10, Letnik:
126, Številka:
8
Journal Article
Recenzirano
Odprti dostop
A central feature of atherosclerosis, the most prevalent chronic vascular disease and root cause of myocardial infarction and stroke, is leukocyte accumulation in the arterial wall. These crucial ...immune cells are produced in specialized niches in the bone marrow, where a complex cell network orchestrates their production and release. A growing body of clinical studies has documented a correlation between leukocyte numbers and cardiovascular disease risk. Understanding how leukocytes are produced and how they contribute to atherosclerosis and its complications is, therefore, critical to understanding and treating the disease. In this review, we focus on the key cells and products that regulate hematopoiesis under homeostatic conditions, during atherosclerosis and after myocardial infarction.
Unhealthy diet, lack of exercise, psychosocial stress, and insufficient sleep are increasingly prevalent modifiable risk factors for cardiovascular disease. Accumulating evidence indicates that these ...risk factors may fuel chronic inflammatory processes that are active in atherosclerosis and lead to myocardial infarction and stroke. In concert with hyperlipidemia, maladaptive immune system activities can contribute to disease progression and increase the probability of adverse events. In this review, we discuss recent insight into how the above modifiable risk factors influence innate immunity. Specifically, we focus on pathways that raise systemic myeloid cell numbers and modulate immune cell phenotypes, reviewing hematopoiesis, leukocyte trafficking, and innate immune cell accumulation in cardiovascular organs. Often, relevant mechanisms that begin with lifestyle choices and lead to cardiovascular events span multiple organ systems, including the central nervous, endocrine, metabolic, hematopoietic, immune and, finally, the cardiovascular system. We argue that deciphering such pathways provides not only support for preventive interventions but also opportunities to develop biomimetic immunomodulatory therapeutics that mitigate cardiovascular inflammation.
Many aspects of human health and disease display daily rhythmicity. The brain’s suprachiasmic nucleus, which interprets recurring external stimuli, and autonomous molecular networks in peripheral ...cells together, set our biological circadian clock. Disrupted or misaligned circadian rhythms promote multiple pathologies including chronic inflammatory and metabolic diseases such as atherosclerosis. Here, we discuss studies suggesting that circadian fluctuations in the vessel wall and in the circulation contribute to atherogenesis. Data from humans and mice indicate that an impaired molecular clock, disturbed sleep, and shifting light–dark patterns influence leukocyte and lipid supply in the circulation and alter cellular behavior in atherosclerotic lesions. We propose that a better understanding of both local and systemic circadian rhythms in atherosclerosis will enhance clinical management, treatment, and public health policy.
Knowledge of macrophages in steady-state and diseased tissue is rapidly expanding, propelled by improved diagnostic capacity to detect and monitor cells in their native environments. In this review, ...we discuss implications for ischaemic heart disease and examine innate immune cell pathways that increase systemic leucocyte supply after myocardial infarction (MI). Acute MI alters the macrophage phenotype and supply chain from tissue resident to blood monocytes sourced from haematopoietic organs. That blood leucocytosis closely associates with cardiovascular mortality provides a strong motivation to understand why and how organ ischaemia alters cellular immunity.
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