Inflammatory cardiomyopathy, characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function, has a heterogeneous aetiology. Inflammatory cardiomyopathy is predominantly mediated by viral infection, but can also be induced by bacterial, protozoal or fungal infections as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases. Despite extensive research, inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis. At present, the reason why some patients recover without residual myocardial injury whereas others develop dilated cardiomyopathy is unclear. The relative roles of the pathogen, host genomics and environmental factors in disease progression and healing are still under discussion, including which viruses are active inducers and which are only bystanders. As a consequence, treatment strategies are not well established. In this Review, we summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with a special focus on virus-induced and virus-associated myocarditis. Furthermore, we identify knowledge gaps, appraise the available experimental models and propose future directions for the field. The current knowledge and open questions regarding the cardiovascular effects associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also discussed. This Review is the result of scientific cooperation of members of the Heart Failure Association of the ESC, the Heart Failure Society of America and the Japanese Heart Failure Society.

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Myocarditis and inflammatory cardiomyopathy: current evidence and future directions.

Preeclampsia is an important complication in pregnancy, characterized by hypertension and proteinuria in the second half of pregnancy. Generalized activation of the inflammatory response is thought to play a role in the pathogenesis of pre-eclampsia. Monocytes may play a central role in this inflammatory response. Monocytes are short lived cells that mature in the circulation and invade into tissues upon an inflammatory stimulus and develop into macrophages. Macrophages are abundantly present in the endometrium and play a role in implantation and placentation in normal pregnancy. In pre-eclampsia, these macrophages appear to be present in larger numbers and are also activated. In the present review, we focused on the role of monocytes and macrophages in the pathophysiology of pre-eclampsia.

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Monocytes and Macrophages in Pregnancy and Pre-Eclampsia

A pan-cancer single-cell transcriptional atlas of tumor infiltrating myeloid cells.

The expansion of adipose tissue (AT) in obesity is accompanied by the accumulation of immune cells that contribute to a state of low-grade, chronic inflammation and dysregulated metabolism. Adipose tissue macrophages (ATMs) represent the most abundant class of leukocytes in AT and are involved in the regulation of several regulatory physiological processes, such as tissue remodeling and insulin sensitivity. With progressive obesity, ATMs are key mediators of meta-inflammation, insulin resistance and impairment of adipocyte function. While macrophage recruitment from blood monocytes is a critical component of the generation of AT inflammation, new studies have revealed a role for ATM proliferation in the early stages of obesity and in sustaining AT inflammation. In addition, studies have revealed a more complex range of macrophage activation states than the previous M1/M2 model, and the existence of different macrophage profiles between human and animal models. This review will summarize the current understanding of the regulatory mechanisms of ATM function in relation to obesity, type 2 diabetes, depot of origin, and to other leukocytes such as AT dendritic cells, with hopes of emphasizing the regulatory nodes that can potentially be targeted to prevent and treat obesity-related metabolic disorders.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/imm.13002

Properties and functions of adipose tissue macrophages in obesity.

Monocytes and macrophages are important components of the immune system, specialized in either removing pathogens as part of innate immunity or contributing to adaptive immunity through antigen presentation. Essential to such functions is classical activation (M1) and alternative activation (M2) of macrophages. M1 polarization of macrophages is characterized by production of pro-inflammatory cytokines, antimicrobial and tumoricidal activity, whereas M2 polarization of macrophages is linked to immunosuppression, tumorigenesis, wound repair, and elimination of parasites. MiRNAs are small non-coding RNAs with the ability to regulate gene expression and network of cellular processes. A number of studies have determined miRNA expression profiles in M1 and M2 polarized human and murine macrophages using microarray and RT-qPCR arrays techniques. More specifically, miR-9, miR-127, miR-155, and miR-125b have been shown to promote M1 polarization while miR-124, miR-223, miR-34a, let-7c, miR-132, miR-146a, and miR-125a-5p induce M2 polarization in macrophages by targeting various transcription factors and adaptor proteins. Further, M1 and M2 phenotypes play distinctive roles in cell growth and progression of inflammation-related diseases such as sepsis, obesity, cancer, and multiple sclerosis. Hence, miRNAs that modulate macrophage polarization may have therapeutic potential in the treatment of inflammation-related diseases. This review highlights recent findings in miRNA expression profiles in polarized macrophages from murine and human sources, and summarizes how these miRNAs regulate macrophage polarization. Last, therapeutic potential of miRNAs in inflammation-related diseases through modulation of macrophage polarization is also discussed.

MiRNA-Mediated Macrophage Polarization and its Potential Role in the Regulation of Inflammatory Response.

Monocytes express various receptors, which monitor and sense environmental changes. Monocytes are highly plastic and heterogeneous, and change their functional phenotype in response to environmental stimulation. Evidence from murine and human studies has suggested that monocytosis can be an indicator of various inflammatory diseases. Monocytes can differentiate into inflammatory or anti-inflammatory subsets. Upon tissue damage or infection, monocytes are rapidly recruited to the tissue, where they can differentiate into tissue macrophages or dendritic cells. Given the rapid progress in monocyte research from broad spectrum of inflammatory diseases, there is a need to summarize our knowledge in monocyte heterogeneity and its impact in human disease. In this review, we describe the current understanding of heterogeneity of human and murine monocytes, the function of distinct subsets of monocytes, and a potential mechanism for monocyte differentiation. We emphasize that inflammatory monocyte subsets are valuable biomarkers for inflammatory diseases, including cardiovascular diseases.

/pdf/monocyte-and-macrophage-differentiation-circulation-3hml6zrzw3.pdf

Monocyte and macrophage differentiation: circulation inflammatory monocyte as biomarker for inflammatory diseases

Rationale:Patients with chronic kidney disease (CKD) develop hyperhomocysteinemia and have a higher cardiovascular mortality than those without hyperhomocysteinemia by 10-fold. Objective:We investi...

Jiyeon Yang

Papers

Monocyte and macrophage differentiation: circulation inflammatory monocyte as biomarker for inflammatory diseases

Chronic Kidney Disease Induces Inflammatory CD40+ Monocyte Differentiation via Homocysteine Elevation and DNA Hypomethylation