Myeloid differentiation factor‐2 activates monocytes in patients with dilated cardiomyopathy

Kümmel, Andreas; Chamling, Bishwas; Strohbach, Anne; Lehnert, Kristin; Groß, Stefan; Loerzer, Lisa; Riad, Alexander; Lindner, Diana; Westermann, Dirk; Fielitz, Jens; Dörr, Marcus; Felix, Stephan B.

doi:10.1111/imm.13490

Cited by 5 publications

(3 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…215 MD-2 directly acts on monocytes and ECs through TLR4/NF-κB pathway to stimulate the synthesis of chemokines and pro-inflammatory cytokines, which could facilitate monocyte recruitment and macrophage activation. 216,217 Moreover, the NLRP3 inflammasome, synthesized by recruited macrophages in DCM, facilitates the cleavage of apoptosisassociated speck-like protein containing a CARD (ASC), caspase-1, IL-1β, IL-18, and gasdermin-D (GSDMD) into active states, which promote inflammation, cardiomyocyte pyroptosis and myocardial fibrosis. 218,219 In genetic DCM, recruited macrophages are also the main source of OPN.…”

Section: Heterogeneity and Regulatory Mechanisms Of Cardiac Macrophag...mentioning

confidence: 99%

Macrophages in cardiovascular diseases: molecular mechanisms and therapeutic targets

Chen,

Zhang,

Tang

et al. 2024

Sig Transduct Target Ther

View full text Add to dashboard Cite

The immune response holds a pivotal role in cardiovascular disease development. As multifunctional cells of the innate immune system, macrophages play an essential role in initial inflammatory response that occurs following cardiovascular injury, thereby inducing subsequent damage while also facilitating recovery. Meanwhile, the diverse phenotypes and phenotypic alterations of macrophages strongly associate with distinct types and severity of cardiovascular diseases, including coronary heart disease, valvular disease, myocarditis, cardiomyopathy, heart failure, atherosclerosis and aneurysm, which underscores the importance of investigating macrophage regulatory mechanisms within the context of specific diseases. Besides, recent strides in single-cell sequencing technologies have revealed macrophage heterogeneity, cell–cell interactions, and downstream mechanisms of therapeutic targets at a higher resolution, which brings new perspectives into macrophage-mediated mechanisms and potential therapeutic targets in cardiovascular diseases. Remarkably, myocardial fibrosis, a prevalent characteristic in most cardiac diseases, remains a formidable clinical challenge, necessitating a profound investigation into the impact of macrophages on myocardial fibrosis within the context of cardiac diseases. In this review, we systematically summarize the diverse phenotypic and functional plasticity of macrophages in regulatory mechanisms of cardiovascular diseases and unprecedented insights introduced by single-cell sequencing technologies, with a focus on different causes and characteristics of diseases, especially the relationship between inflammation and fibrosis in cardiac diseases (myocardial infarction, pressure overload, myocarditis, dilated cardiomyopathy, diabetic cardiomyopathy and cardiac aging) and the relationship between inflammation and vascular injury in vascular diseases (atherosclerosis and aneurysm). Finally, we also highlight the preclinical/clinical macrophage targeting strategies and translational implications.

show abstract

Section: Heterogeneity and Regulatory Mechanisms Of Cardiac Macrophag...mentioning

confidence: 99%

Macrophages in cardiovascular diseases: molecular mechanisms and therapeutic targets

Chen,

Zhang,

Tang

et al. 2024

Sig Transduct Target Ther

View full text Add to dashboard Cite

show abstract

“…MD-2 is a 20–25 kDa protein that can be found in plasma or associated with the membrane, and it is in close proximity to TLR4 [ 61 , 62 ]. Feldtmann et al [ 63 ] demonstrated that MD-2 can induce a pro-inflammatory state in monocytes and endothelial cells through TLR4/NF-κB signaling in patients with DCM. MD-2 activation of endothelial cells results in the secretion of monocyte-chemoattractant protein-1 (MCP-1) and increased expression of adhesion molecules CD54, CD106, and CD62E, thereby promoting enhanced monocyte recruitment and the progression of DCM.…”

Section: Regulatory Mechanisms Of Immune Cells In Dcmmentioning

confidence: 99%

The Molecular Role of Immune Cells in Dilated Cardiomyopathy

Wang

Zhou

et al. 2023

Medicina

View full text Add to dashboard Cite

Dilated cardiomyopathy (DCM) is a rare and severe condition characterized by chamber dilation and impaired contraction of the left ventricle. It constitutes a fundamental etiology for profound heart failure and abrupt cardiac demise, rendering it a prominent clinical indication for heart transplantation (HTx) among both adult and pediatric populations. DCM arises from various etiologies, including genetic variants, epigenetic disorders, infectious insults, autoimmune diseases, and cardiac conduction abnormalities. The maintenance of cardiac function involves two distinct types of immune cells: resident immune cells and recruited immune cells. Resident immune cells play a crucial role in establishing a harmonious microenvironment within the cardiac tissue. Nevertheless, in response to injury, cardiomyocytes initiate a cytokine cascade that attracts peripheral immune cells, thus perturbing this intricate equilibrium and actively participating in the initiation and pathological remodeling of dilated cardiomyopathy (DCM), particularly during the progression of myocardial fibrosis. Additionally, immune cells assume a pivotal role in orchestrating the inflammatory processes, which are intimately linked to the prognosis of DCM. Consequently, understanding the molecular role of various immune cells and their regulation mechanisms would provide an emerging era for managing DCM. In this review, we provide a summary of the most recent advancements in our understanding of the molecular mechanisms of immune cells in DCM. Additionally, we evaluate the effectiveness and limitations of immunotherapy approaches for the treatment of DCM, with the aim of optimizing future immunotherapeutic strategies for this condition.

show abstract

“…Studies have revealed that many pathogenic pathways, including metabolism and immunological inflammation, are connected to the incidence and progression of DCM. [2][3][4] A variety of cell deaths have been reported to be involved in the development of DCM including apoptosis, autophagy and pyroptosis. [5][6][7] However, as one of the important types of cell death, the role of ferroptosis in DCM has not been clearly elucidated.…”

Section: Introductionmentioning

confidence: 99%

Identification of Novel Targets for Treatment of Dilated Cardiomyopathy Based on the Ferroptosis and Immune Heterogeneity

Lu¹,

Xie²,

Zhou³

et al. 2023

JIR

View full text Add to dashboard Cite

Purpose This study aimed to investigate the role of ferroptosis in dilated cardiomyopathy (DCM) and to identify new targets for treatment and diagnosis of DCM. Methods GSE116250 and GSE145154 were downloaded from the Gene Expression Omnibus database. Unsupervised consensus clustering of DCM patients was used to confirm the impact of ferroptosis. Ferroptosis-related hub genes were identified by WGCNA and single cell sequencing analyses. Finally, we established a DCM mouse model via injection of Doxorubicin to verify the expression level of OTUD1 and colocalization between cell markers and OTUD1 in DCM mouse heart. Results A total of 13 ferroptosis-related differentially expressed genes (DEGs) were identified. The DCM patients were divided into two clusters according to the expression of 13 DEGs. The DCM patients in different clusters showed discrepancies in immune infiltration. Four hub genes were further identified by WGCNA analysis. Single cell data analysis revealed that OTUD1 may regulate B cells and DC cells and then participate in immune infiltration discrepancy. The upregulation of OTUD1 and the colocalization of OTUD1 with CD19 (B cell maker) and CD11c (DCs markers) markers were confirmed in DCM mouse hearts. Conclusion Ferroptosis and the immune microenvironment are closely associated with DCM, and OTUD1 may play an important role through B cells and DCs.

show abstract

Myeloid differentiation factor‐2 activates monocytes in patients with dilated cardiomyopathy

Cited by 5 publications

References 38 publications

Macrophages in cardiovascular diseases: molecular mechanisms and therapeutic targets

Macrophages in cardiovascular diseases: molecular mechanisms and therapeutic targets

The Molecular Role of Immune Cells in Dilated Cardiomyopathy

Identification of Novel Targets for Treatment of Dilated Cardiomyopathy Based on the Ferroptosis and Immune Heterogeneity

Contact Info

Product

Resources

About