A cardioimmunologist’s toolkit: genetic tools to dissect immune cells in cardiac disease

Wong, Anthony; Hamidzada, Homaira; Epelman, Slava

doi:10.1038/s41569-022-00701-0

Cited by 18 publications

(6 citation statements)

References 244 publications

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“…www.nature.com/scientificreports/ positive populations were present among macrophages (CD45+, CD11b+, CD64+, Ly6c low) (18.9 ± 0.8%) and neutrophils (CD45+, CD11b+, Ly6G+) (27.7 ± 2.9%) as described in a previous paper 5 . Furthermore, some cardiac resident macrophages (CD45+, CD11b+, CD64+, Ly6c low, CCR2−, MHC2 low) (18.4 ± 1.1%) and MHC2 high macrophage (CD45+, CD11b+, CD64+, Ly6c low, CCR2-, MHC2 high) (20.0 ± 1.0%), both of which are derived from the yolk sac or fetal liver 9,10 , expressed GFP (Fig. 2a-c).…”

mentioning

confidence: 98%

Smooth muscle protein 22α-Cre recombination in resting cardiac fibroblasts and hematopoietic precursors

Ikeda

Sugioka

Kimura

et al. 2022

Sci Rep

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The Cre-loxP system has been widely used for cell- or organ-specific gene manipulation, but it is important to precisely understand what kind of cells the recombination takes place in. Smooth muscle 22α (SM22α)-Cre mice have been utilized to alter genes in vascular smooth muscle cells (VSMCs), activated fibroblasts or cardiomyocytes (CMs). Moreover, previous reports indicated that SM22α-Cre is expressed in adipocytes, platelets or myeloid cells. However, there have been no report of whether SM22α-Cre recombination takes place in nonCMs in hearts. Thus, we used the double-fluorescent Cre reporter mouse in which GFP is expressed when recombination occurs. Immunofluorescence analysis demonstrated that recombination occurred in resting cardiac fibroblasts (CFs) or macrophages, as well as VSMCs and CMs. Flow cytometry showed that some CFs, resident macrophages, neutrophils, T cells, and B cells were positive for GFP. These results prompted us to analyze bone marrow cells, and we observed GFP-positive hematopoietic precursor cells (HPCs). Taken together, these results indicated that SM22α-Cre-mediated recombination occurs in resting CFs and hematopoietic cell lineages, including HPCs, which is a cautionary point when using SM22α-Cre mice.

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confidence: 98%

Smooth muscle protein 22α-Cre recombination in resting cardiac fibroblasts and hematopoietic precursors

Ikeda

Sugioka

Kimura

et al. 2022

Sci Rep

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“…Here, we will briefly discuss the tools used to assess both to provide context (as recently reviewed in detail). 8 Developmental studies typically use genetic fate mapping to track macrophage origins. In the mouse, macrophages are first observed from a wave of primitive hematopoiesis in the extra-embryonic yolk sac (YS) between embryonic days (E)6.5 to 8.5, in addition to red blood cells and megakaryocytes that form platelets.…”

Section: Origin Of Resident Cardiac Macrophagesmentioning

confidence: 99%

“…4 Importantly, immune cells, in particular monocytes and macrophages, are increasingly appreciated to be novel regulators of both tissue injury and repair. [5][6][7][8][9] Although progress has been made, we lack an understanding of how immune mechanisms modulate the initial injury and reparative responses, and the downstream development of HF. As a result, immunemediated pathways have not been well explored clinically for diagnostic, prognostic, or therapeutic utility.…”

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confidence: 99%

Dissecting and Visualizing the Functional Diversity of Cardiac Macrophages

Holt,

Lin,

Cicka

et al. 2024

Circulation Research

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Cardiac macrophages represent a functionally diverse population of cells involved in cardiac homeostasis, repair, and remodeling. With recent advancements in single-cell technologies, it is possible to elucidate specific macrophage subsets based on transcriptional signatures and cell surface protein expression to gain a deep understanding of macrophage diversity in the heart. The use of fate-mapping technologies and parabiosis studies have provided insight into the ontogeny and dynamics of macrophages identifying subsets derived from embryonic and adult definitive hematopoietic progenitors that include tissue-resident and bone marrow monocyte-derived macrophages, respectively. Within the heart, these subsets have distinct tissue niches and functional roles in the setting of homeostasis and disease, with cardiac resident macrophages representing a protective cell population while bone marrow monocyte-derived cardiac macrophages have a context-dependent effect, triggering both proinflammatory tissue injury, but also promoting reparative functions. With the increased understanding of the clinical relevance of cardiac macrophage subsets, there has been an increasing need to detect and measure cardiac macrophage compositions in living animals and patients. New molecular tracers compatible with positron emission tomography/computerized tomography and positron emission tomography/ magnetic resonance imaging have enabled investigators to noninvasively and serially visualize cardiac macrophage subsets within the heart to define associations with disease and measure treatment responses. Today, advancements within this thriving field are poised to fuel an era of clinical translation.

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“…While the role of inflammation and immunity in HHD and heart failure has long been recognized, the understanding of this process has been limited by the knowledge of the immune environment in the heart and the available research methods. Recent advancements in fate mapping and single-cell analysis techniques have provided valuable opportunities for advancing cardiac immunology [ 85 ]. These tools have revealed the heterogeneity of the cardiac immune system, offering new insights into the roles of immunity and inflammation in HHD.…”

Section: Mechanisms Contributing To Hypertensive Heart Diseasementioning

confidence: 99%

Hypertensive Heart Disease: Mechanisms, Diagnosis and Treatment

Huang,

Hu,

Long

et al. 2024

Rev. Cardiovasc. Med.

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Hypertensive heart disease (HHD) presents a substantial global health burden, spanning a spectrum from subtle cardiac functional alterations to overt heart failure. In this comprehensive review, we delved into the intricate pathophysiological mechanisms governing the onset and progression of HHD. We emphasized the significant role of neurohormonal activation, inflammation, and metabolic remodeling in HHD pathogenesis, offering insights into promising therapeutic avenues. Additionally, this review provided an overview of contemporary imaging diagnostic tools for precise HHD severity assessment. We discussed in detail the current potential treatments for HHD, including pharmacologic, lifestyle, and intervention devices. This review aimed to underscore the global importance of HHD and foster a deeper understanding of its pathophysiology, ultimately contributing to improved public health outcomes.

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A cardioimmunologist’s toolkit: genetic tools to dissect immune cells in cardiac disease

Cited by 18 publications

References 244 publications

Smooth muscle protein 22α-Cre recombination in resting cardiac fibroblasts and hematopoietic precursors

Smooth muscle protein 22α-Cre recombination in resting cardiac fibroblasts and hematopoietic precursors

Dissecting and Visualizing the Functional Diversity of Cardiac Macrophages

Hypertensive Heart Disease: Mechanisms, Diagnosis and Treatment

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