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Open AccessJournal ArticleDOI

Lymphatic Clearance of Immune Cells in Cardiovascular Disease

TLDR
In this article, the authors examined the different types of immune cells involved in fibrotic repair following myocardial infarction and discussed the development and function of the cardiac lymphatic vasculature and how some immune cells interact with the lymphatic endothelium.
Abstract
Recent advances in our understanding of the lymphatic system, its function, development, and role in pathophysiology have changed our views on its importance. Historically thought to be solely involved in the transport of tissue fluid, lipids, and immune cells, the lymphatic system displays great heterogeneity and plasticity and is actively involved in immune cell regulation. Interference in any of these processes can be deleterious, both at the developmental and adult level. Preclinical studies into the cardiac lymphatic system have shown that invoking lymphangiogenesis and enhancing immune cell trafficking in ischaemic hearts can reduce myocardial oedema, reduce inflammation, and improve cardiac outcome. Understanding how immune cells and the lymphatic endothelium interact is also vital to understanding how the lymphatic vascular network can be manipulated to improve immune cell clearance. In this Review, we examine the different types of immune cells involved in fibrotic repair following myocardial infarction. We also discuss the development and function of the cardiac lymphatic vasculature and how some immune cells interact with the lymphatic endothelium in the heart. Finally, we establish how promoting lymphangiogenesis is now a prime therapeutic target for reducing immune cell persistence, inflammation, and oedema to restore heart function in ischaemic heart disease.

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Journal ArticleDOI

Regulation and impact of cardiac lymphangiogenesis in pressure-overload-induced heart failure

TL;DR: In this article , the authors investigated cardiac lymphangiogenesis following transversal aortic constriction (TAC) in C57Bl/6 and Balb/c mice, and in end-stage heart failure patients.
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Lymphatic endothelial sphingosine 1-phosphate receptor 1 enhances macrophage clearance via lymphatic system following myocardial infarction

TL;DR: Cardiac lymphatic endothelial cells tightly control macrophage trafficking via lymphatic vessels in injured hearts via S1P/S1pr1/ERK/CCL2 pathway and thus regulate post-MI immune modulation and heart repair.
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Cardiac lymphatics: state of the art

TL;DR: In this article , the beneficial role of cardiac lymphatics in health and disease has begun to be recognized, with both preclinical and clinical evidence demonstrating that lymphangiogenesis is activated in cardiovascular diseases.
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The multifaceted nature of endogenous cardiac regeneration

TL;DR: In this paper , the authors highlight a variety of processes that have been identified as being essential for cardiac regeneration in zebrafish and neonatal mice and highlight a number of different cell types, signaling pathways and mechanisms that must all work in harmony in order for regeneration to occur.
Journal ArticleDOI

Differential regulation of lymphatic junctional morphology and the potential effects on cardiovascular diseases

TL;DR: In this article , the effect of junctional morphology on lymphatic flow and lymphatic permeability is discussed, with a focus on atherosclerosis in the thoracic and subclavian vein.
References
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Journal ArticleDOI

Cytokine Storm in a Phase 1 Trial of the Anti-CD28 Monoclonal Antibody TGN1412

TL;DR: Six healthy young male volunteers at a contract research organization were enrolled in the first phase 1 clinical trial of TGN1412, a novel superagonist anti-CD28 monoclonal antibody that directly stimulates T cells, and experienced a systemic inflammatory response characterized by a rapid induction of proinflammatory cytokines.
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The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions

TL;DR: This work identifies two distinct phases of monocyte participation after MI and proposes a model that reconciles the divergent properties of these cells in healing and identifies new therapeutic targets that can influence healing and ventricular remodeling after MI.
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Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors

TL;DR: It is shown in mice that the vast majority of adult tissue-resident macrophages originate from a Tie2+ (also known as Tek) cellular pathway generating Csf1r+ erythro-myeloid progenitors (EMPs) distinct from HSCs.
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Prox1 Function Is Required for the Development of the Murine Lymphatic System

TL;DR: It is reported that the homeobox gene Prox1 is expressed in a subpopulation of endothelial cells that by budding and sprouting give rise to the lymphatic system, suggesting that unidentified guidance signals regulate this process.
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