MD-2 is a new predictive biomarker in dilated cardiomyopathy and exerts direct effects in isolated cardiomyocytes

Riad, Alexander; Groß, Stefan; Witte, Jeannine; Strohbach, Anne; Wagner, Katharina B; Reinke, Yvonne; Weitmann, Kerstin; Empen, Klaus; Beug, Daniel; Westermann, Dirk; Lindner, Diana; Klingel, Karin; Dörr, Marcus; Hoffmann, Wolfgang; Felix, Stephan B.

doi:10.1016/j.ijcard.2018.06.025

Cited by 7 publications

(6 citation statements)

References 48 publications

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“…Recent studies suggest a strong contribution of TLR4 signalling in systemic inflammatory diseases and report an involvement of MD-2 plasma levels in this context [12,25]. Recently, we described elevated MD-2 plasma levels in patients with DCM indicating that MD-2 is a prognostic biomarker in DCM [13]. These findings emphasize the importance of innate immunity in disease progression.…”

Section: Discussionsupporting

confidence: 69%

“…Recently, we reported that elevated MD-2 plasma levels independently predict all-cause mortality in DCM patients [13]. We also showed that the combined measurement of NT-proBNP and MD-2 in plasma significantly improved mortality risk prediction in DCM patients compared to NT-proBNP alone [13]. Furthermore, we demonstrated that MD-2 mediates negative inotropic effects on isolated cardiomyocytes in vitro [13].…”

Section: Introductionmentioning

confidence: 83%

“…We also showed that the combined measurement of NT‐proBNP and MD‐2 in plasma significantly improved mortality risk prediction in DCM patients compared to NT‐proBNP alone [13]. Furthermore, we demonstrated that MD‐2 mediates negative inotropic effects on isolated cardiomyocytes in vitro [13]. Inflammation plays an important role in the pathophysiology of heart failure.…”

Section: Introductionmentioning

confidence: 99%

“…MD‐2 is a 20–25 kDa protein that occurs either as plasma protein or is membrane bound and co‐localized with TLR4 [12]. Recently, we reported that elevated MD‐2 plasma levels independently predict all‐cause mortality in DCM patients [13]. We also showed that the combined measurement of NT‐proBNP and MD‐2 in plasma significantly improved mortality risk prediction in DCM patients compared to NT‐proBNP alone [13].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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Plasma levels of myeloid differentiation factor-2 (MD-2), a co-receptor of toll-like-receptor 4 (TLR4), independently predict mortality in patients with dilated cardiomyopathy (DCM). We tested whether monocyte activation by MD-2 contributes to immune activation and inflammatory status in DCM patients. We found increased MD-2 plasma levels in 25 patients with recent-onset DCM (1250 AE 80.7 ng/ml) compared to 25 age-and gender-matched healthy controls (793.4 AE 52.0 ng/ml; p < 0.001). Monocytes isolated from DCM patients showed a higher expression (141.7 AE 12.4%; p = 0.006 vs. controls) of the MD-2 encoding gene, LY96 and an increased NF-κB-activation. Further, the TLR4-activator lipopolysaccharide (LPS) caused a higher increase in interleukin (IL)-6 in monocytes from DCM patients compared to controls (mean fluorescence intensity: 938.7 AE 151.0 vs. 466.9 AE 51.1; p = 0.005). MD-2 increased IL-6 secretion in a TLR4/NF-κB-dependent manner in monocyte-like THP-1-cells as demonstrated by TLR4-siRNA and NF-κB-inhibition. Since endothelial cells (ECs) are responsible for recruiting monocytes to the site of inflammation, ECs were treated with MD-2 leading to an activation of Akt and increased secretion of monocyte-chemoattractantprotein-1 (MCP-1).

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Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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“…Number of studies investigated the role of MD2 as biomarker for several CVDs. The clinical study by Riad et al assessed the predictive value of MD2 in dilated cardiomyopathy (DCM) ( 65 ). DCM is characterized by ventricular chamber enlargement and systolic dysfunction, with most cases being idiopathic.…”

Section: Tlr Accessory Molecules That Act As Cofactors Required For C...mentioning

confidence: 99%

The Intriguing Role of TLR Accessory Molecules in Cardiovascular Health and Disease

Bezhaeva

Karper²,

Quax

et al. 2022

Front. Cardiovasc. Med.

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Activation of Toll like receptors (TLR) plays an important role in cardiovascular disease development, progression and outcomes. Complex TLR mediated signaling affects vascular and cardiac function including tissue remodeling and repair. Being central components of both innate and adaptive arms of the immune system, TLRs interact as pattern recognition receptors with a series of exogenous ligands and endogenous molecules or so-called danger associated molecular patterns (DAMPs) that are released upon tissue injury and cellular stress. Besides immune cells, a number of structural cells within the cardiovascular system, including endothelial cells, smooth muscle cells, fibroblasts and cardiac myocytes express TLRs and are able to release or sense DAMPs. Local activation of TLR-mediated signaling cascade induces cardiovascular tissue repair but in a presence of constant stimuli can overshoot and cause chronic inflammation and tissue damage. TLR accessory molecules are essential in guiding and dampening these responses toward an adequate reaction. Furthermore, accessory molecules assure specific and exclusive TLR-mediated signal transduction for distinct cells and pathways involved in the pathogenesis of cardiovascular diseases. Although much has been learned about TLRs activation in cardiovascular remodeling, the exact role of TLR accessory molecules is not entirely understood. Deeper understanding of the role of TLR accessory molecules in cardiovascular system may open therapeutic avenues aiming at manipulation of inflammatory response in cardiovascular disease. The present review outlines accessory molecules for membrane TLRs that are involved in cardiovascular disease progression. We first summarize the up-to-date knowledge on TLR signaling focusing on membrane TLRs and their ligands that play a key role in cardiovascular system. We then survey the current evidence of the contribution of TLRs accessory molecules in vascular and cardiac remodeling including myocardial infarction, heart failure, stroke, atherosclerosis, vein graft disease and arterio-venous fistula failure.

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High-Mobility Group Box Protein 1 Is an Independent Prognostic Marker for All-Cause Mortality in Patients With Dilated Cardiomyopathy

Kümmel

Groß

Chamling

et al. 2022

The American Journal of Cardiology

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MD-2 is a new predictive biomarker in dilated cardiomyopathy and exerts direct effects in isolated cardiomyocytes

Cited by 7 publications

References 48 publications

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

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

The Intriguing Role of TLR Accessory Molecules in Cardiovascular Health and Disease

High-Mobility Group Box Protein 1 Is an Independent Prognostic Marker for All-Cause Mortality in Patients With Dilated Cardiomyopathy

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