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Article ; Online: The C0-C1f Region of Cardiac Myosin Binding Protein-C Induces Pro-Inflammatory Responses in Fibroblasts via TLR4 Signaling.

Yogeswaran, Athiththan / Troidl, Christian / McNamara, James W / Wilhelm, Jochen / Truschel, Theresa / Widmann, Laila / Aslam, Muhammad / Hamm, Christian W / Sadayappan, Sakthivel / Lipps, Christoph

Cells

2021 Volume 10, Issue 6

Abstract: Myocardial injury is associated with inflammation and fibrosis. Cardiac myosin-binding protein-C ... cMyBP-C) is cleaved by µ-calpain upon myocardial injury, releasing C0-C1f, an ...

Abstract	Myocardial injury is associated with inflammation and fibrosis. Cardiac myosin-binding protein-C (cMyBP-C) is cleaved by µ-calpain upon myocardial injury, releasing C0-C1f, an
MeSH term(s)	Actins/metabolism ; Cytoskeletal Proteins/metabolism ; Fibroblasts/metabolism ; Humans ; Myofibroblasts/metabolism ; Sarcomeres/metabolism ; Toll-Like Receptor 4/metabolism
Chemical Substances	Actins ; Cytoskeletal Proteins ; Toll-Like Receptor 4
Language	English
Publishing date	2021-05-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10061326
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Article ; Online: Evaluation of cystatin C and neutrophil gelatinase-associated lipocalin as predictors of mortality in patients undergoing percutaneous mitral valve repair (MitraClip).

Dörr, Oliver / Walther, Claudia / Liebetrau, Christoph / Keller, Till / Ortlieb, Regine M / Boeder, Niklas / Bauer, Pascal / Möllmann, Helge / Gaede, Luise / Troidl, Christian / Voss, Sandra / Bauer, Timm / Hamm, Christian W / Nef, Holger

Clinical cardiology

2018 Volume 41, Issue 11, Page(s) 1474–1479

Abstract: ... with poor outcome in patients with mitral regurgitation (MR) and heart failure. Cystatin C ... cystatin C and urinary NGAL as indicators of mortality in patients undergoing percutaneous mitral valve ... class (P < 0.01) was documented. Baseline levels of serum cystatin C (nonsurvivors: 2.4 mg/L ...

Abstract	Background: Compromised renal function is a major risk factor that is strongly associated with poor outcome in patients with mitral regurgitation (MR) and heart failure. Cystatin C, a cysteine protease inhibitor, has been used as a specific and sensitive biomarker of renal function. Neutrophil gelatinase-associated lipocalin (NGAL) is another sensitive biomarker that specifically indicates functional and structural kidney damage. The aim of the present study was to determine the predictive value of serum cystatin C and urinary NGAL as indicators of mortality in patients undergoing percutaneous mitral valve repair (PMVR). Methods: A total of 120 consecutive patients (age: 77.3 years [±11.2]) undergoing PMVR using the MitraClip system were included in this study. Venous blood and urinary samples were collected for biomarker analysis prior to PMVR. Physiological parameters, medication use, safety events, and all-cause mortality were assessed 12 months after the procedure. Results: Twelve months after PMVR, there was a significant reduction in the severity of MR (P < 0.001), and an improvement in the New York Heart Association class (P < 0.01) was documented. Baseline levels of serum cystatin C (nonsurvivors: 2.4 mg/L [interquartile, IQR: 1.7;3.1] vs survivors: 1.7 mg/L [IQR: 1,3;2.1], P < 0.001) and urinary NGAL (nonsurvivors: 242.0 ng/mL [IQR: 154.5;281.5] vs survivors: 132.0 ng/mL [IQR:107.0;177.3], P < 0.001) were significantly higher in patients who died during the 12-month follow-up period. Conclusion: Cystatin C and urinary NGAL were found to be predictors of long-term mortality in high-risk patients undergoing PMVR. Thus, cystatin C and NGAL assessment may be helpful in risk stratification in patients undergoing PMVR.
MeSH term(s)	Aged ; Aged, 80 and over ; Biomarkers/blood ; Biomarkers/urine ; Cardiac Catheterization/adverse effects ; Cardiac Catheterization/instrumentation ; Cardiac Catheterization/mortality ; Cystatin C/blood ; Female ; Heart Valve Prosthesis ; Heart Valve Prosthesis Implantation/adverse effects ; Heart Valve Prosthesis Implantation/instrumentation ; Heart Valve Prosthesis Implantation/mortality ; Humans ; Kidney/physiopathology ; Kidney Diseases/complications ; Kidney Diseases/metabolism ; Kidney Diseases/mortality ; Kidney Diseases/physiopathology ; Lipocalin-2/urine ; Male ; Mitral Valve/physiopathology ; Mitral Valve/surgery ; Mitral Valve Insufficiency/complications ; Mitral Valve Insufficiency/mortality ; Mitral Valve Insufficiency/physiopathology ; Mitral Valve Insufficiency/surgery ; Predictive Value of Tests ; Prosthesis Design ; Recovery of Function ; Risk Factors ; Time Factors ; Treatment Outcome
Chemical Substances	Biomarkers ; CST3 protein, human ; Cystatin C ; LCN2 protein, human ; Lipocalin-2
Language	English
Publishing date	2018-11-16
Publishing country	United States
Document type	Journal Article ; Observational Study
ZDB-ID	391935-3
ISSN	1932-8737 ; 0160-9289
ISSN (online)	1932-8737
ISSN	0160-9289
DOI	10.1002/clc.23089
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Article ; Online: N-terminal fragment of cardiac myosin binding protein-C triggers pro-inflammatory responses in vitro.

Lipps, Christoph / Nguyen, Jenine H / Pyttel, Lukas / Lynch, Thomas L / Liebetrau, Christoph / Aleshcheva, Ganna / Voss, Sandra / Dörr, Oliver / Nef, Holger M / Möllmann, Helge / Hamm, Christian W / Sadayappan, Sakthivel / Troidl, Christian

Journal of molecular and cellular cardiology

2016 Volume 99, Page(s) 47–56

Abstract: ... cells of the immune system. Recently, it was shown that cardiac myosin binding protein-C (cMyBP-C), a protein ...

Abstract	Myocardial infarction (MI) leads to loss and degradation of contractile cardiac tissue followed by sterile inflammation of the myocardium through activation and recruitment of innate and adaptive cells of the immune system. Recently, it was shown that cardiac myosin binding protein-C (cMyBP-C), a protein of the cardiac sarcomere, is degraded following MI, releasing a predominant N-terminal 40-kDa fragment (C0C1f) into myocardial tissue and the systemic circulation. We hypothesized that early release of C0C1f contributes to the initiation of inflammation and plays a key role in recruitment and activation of immune cells. Therefore, we investigated the role of C0C1f on macrophage/monocyte activation using both mouse bone marrow-derived macrophages and human monocytes. Here we demonstrate that C0C1f leads to macrophage/monocyte activation in vitro. Furthermore, C0C1f induces strong upregulation of pro-inflammatory cytokines (interleukin-6 (IL-6), tumor necrosis factor α (TNFα), and interleukin-1β (IL-1β)) in cultured murine macrophages and human monocytes, resulting in a pro-inflammatory phenotype. We identified the toll-like receptor 4 (TLR4), toll-like receptor 2 (TLR2), and Advanced Glycosylation End Product-Specific Receptor (RAGE) as potential receptors for C0C1f whose activation leads to mobilization of the NFκB signaling pathway, a central mediator of the pro-inflammatory signaling cascade. Thus, C0C1f appears to be a key player in the initiation of inflammatory processes and might also play an important role upon MI.
MeSH term(s)	Animals ; Carrier Proteins/chemistry ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cytokines/metabolism ; Gene Expression ; Humans ; Inflammation/genetics ; Inflammation/metabolism ; Inflammation Mediators/metabolism ; Macrophages/immunology ; Macrophages/metabolism ; Mice ; Monocytes/immunology ; Monocytes/metabolism ; NF-kappa B/metabolism ; Protein Interaction Domains and Motifs ; Receptor for Advanced Glycation End Products/metabolism ; Signal Transduction ; Toll-Like Receptor 2/metabolism ; Toll-Like Receptor 4/metabolism
Chemical Substances	Carrier Proteins ; Cytokines ; Inflammation Mediators ; NF-kappa B ; Receptor for Advanced Glycation End Products ; Toll-Like Receptor 2 ; Toll-Like Receptor 4 ; myosin-binding protein C
Language	English
Publishing date	2016-10
Publishing country	England
Document type	Journal Article
ZDB-ID	80157-4
ISSN	1095-8584 ; 0022-2828
ISSN (online)	1095-8584
ISSN	0022-2828
DOI	10.1016/j.yjmcc.2016.09.003
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Article ; Online: The C0-C1f Region of Cardiac Myosin Binding Protein-C Induces Pro-Inflammatory Responses in Fibroblasts via TLR4 Signaling

Athiththan Yogeswaran / Christian Troidl / James W. McNamara / Jochen Wilhelm / Theresa Truschel / Laila Widmann / Muhammad Aslam / Christian W. Hamm / Sakthivel Sadayappan / Christoph Lipps

Cells, Vol 10, Iss 1326, p

2021 Volume 1326

Abstract: Myocardial injury is associated with inflammation and fibrosis. Cardiac myosin-binding protein-C ... cMyBP-C) is cleaved by µ-calpain upon myocardial injury, releasing C0-C1f, an N -terminal peptide ... of cMyBP-C. Previously, we reported that the presence of C0-C1f is pathogenic within cardiac tissue and is ...

Abstract	Myocardial injury is associated with inflammation and fibrosis. Cardiac myosin-binding protein-C (cMyBP-C) is cleaved by µ-calpain upon myocardial injury, releasing C0-C1f, an N -terminal peptide of cMyBP-C. Previously, we reported that the presence of C0-C1f is pathogenic within cardiac tissue and is able to activate macrophages. Fibroblasts also play a crucial role in cardiac remodeling arising from ischemic events, as they contribute to both inflammation and scar formation. To understand whether C0-C1f directly modulates fibroblast phenotype, we analyzed the impact of C0-C1f on a human fibroblast cell line in vitro by performing mRNA microarray screening, immunofluorescence staining, and quantitative real-time PCR. The underlying signaling pathways were investigated by KEGG analysis and determined more precisely by targeted inhibition of the potential signaling cascades in vitro. C0-C1f induced pro-inflammatory responses that might delay TGFβ-mediated myofibroblast conversion. TGFβ also counteracted C0-C1f-mediated fibroblast activation. Inhibition of TLR4 or NFκB as well as the delivery of miR-146 significantly reduced C0-C1f-mediated effects. In conclusion, C0-C1f induces inflammatory responses in human fibroblasts that are mediated via TRL4 signaling, which is decreased in the presence of TGFβ. Specific targeting of TLR4 signaling could be an innovative strategy to modulate C0-C1f-mediated inflammation.
Keywords	fibroblasts ; inflammation ; MYBPC3 ; C0-C1f ; cMyBP-C ; miRNA-146 ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Cardiac Myosin Binding Protein-C Autoantibodies are Potential Early Indicators of Cardiac Dysfunction and Patient Outcome in Acute Coronary Syndrome.

Lynch, Thomas L / Kuster, Diederik W D / Gonzalez, Beverly / Balasubramanian, Neelam / Nair, Nandini / Day, Sharlene / Calvino, Jenna E / Tan, Yanli / Liebetrau, Christoph / Troidl, Christian / Hamm, Christian W / Güçlü, Ahmet / McDonough, Barbara / Marian, Ali J / van der Velden, Jolanda / Seidman, Christine E / Huggins, Gordon S / Sadayappan, Sakthivel

JACC. Basic to translational science

2016 Volume 2, Issue 2, Page(s) 122–131

Abstract: The degradation and release of cardiac myosin binding protein-C (cMyBP-C) upon cardiac damage ... of cMyBP-C-AAbs associated with adverse cardiac function in CVD patients. Importantly, cMyBP-C-AAbs were ... patients. Patients positive for cMyBP-C-AAbs had a reduced LVEF and elevated levels of clinical biomarkers ...

Abstract	The degradation and release of cardiac myosin binding protein-C (cMyBP-C) upon cardiac damage may stimulate an inflammatory response and autoantibody (AAb) production. We determined whether the presence of cMyBP-C-AAbs associated with adverse cardiac function in CVD patients. Importantly, cMyBP-C-AAbs were significantly detected in ACS patient sera upon arrival to the emergency department, particularly in STEMI patients. Patients positive for cMyBP-C-AAbs had a reduced LVEF and elevated levels of clinical biomarkers of MI. We conclude that cMyBP-C-AAbs may serve as early predictive indicators of deteriorating cardiac function and patient outcome in ACS patients prior to the infarction.
Language	English
Publishing date	2016-12-19
Publishing country	United States
Document type	Journal Article
ISSN	2452-302X
ISSN	2452-302X
DOI	10.1016/j.jacbts.2016.12.001
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Article ; Online: Release kinetics of circulating cardiac myosin binding protein-C following cardiac injury.

Kuster, Diederik W D / Cardenas-Ospina, Adriana / Miller, Lawson / Liebetrau, Christoph / Troidl, Christian / Nef, Holger M / Möllmann, Helge / Hamm, Christian W / Pieper, Karen S / Mahaffey, Kenneth W / Kleiman, Neal S / Stuyvers, Bruno D / Marian, Ali J / Sadayappan, Sakthivel

American journal of physiology. Heart and circulatory physiology

2013 Volume 306, Issue 4, Page(s) H547–56

Abstract: ... early biomarker of MI, this study investigates the release kinetics of cardiac myosin binding protein-C ... cMyBP-C) in a porcine model of MI and in two human cohorts. Release kinetics of cMyBP-C were determined ... in a porcine model of MI (n = 6, pigs, either sex) by measuring plasma cMyBP-C level serially from 30 min to 14 ...

Abstract	Diagnosis of myocardial infarction (MI) is based on ST-segment elevation on electrocardiographic evaluation and/or elevated plasma cardiac troponin (cTn) levels. However, troponins lack the sensitivity required to detect the onset of MI at its earliest stages. Therefore, to confirm its viability as an ultra-early biomarker of MI, this study investigates the release kinetics of cardiac myosin binding protein-C (cMyBP-C) in a porcine model of MI and in two human cohorts. Release kinetics of cMyBP-C were determined in a porcine model of MI (n = 6, pigs, either sex) by measuring plasma cMyBP-C level serially from 30 min to 14 days after coronary occlusion, with use of a custom-made immunoassay. cMyBP-C plasma levels were increased from baseline (76 ± 68 ng/l) at 3 h (767 ± 211 ng/l) and peaked at 6 h (2,418 ± 780 ng/l) after coronary ligation. Plasma cTnI, cTnT, and myosin light chain-3 levels were all increased 6 h after ligation. In a cohort of patients (n = 12) with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy, cMyBP-C was significantly increased from baseline (49 ± 23 ng/l) in a time-dependent manner, peaking at 4 h (560 ± 273 ng/l). In a cohort of patients with non-ST segment elevation MI (n = 176) from the SYNERGY trial, cMyBP-C serum levels were significantly higher (7,615 ± 4,514 ng/l) than those in a control cohort (416 ± 104 ng/l; n = 153). cMyBP-C is released in the blood rapidly after cardiac damage and therefore has the potential to positively mark the onset of MI.
MeSH term(s)	Animals ; Biomarkers/blood ; Carrier Proteins/blood ; Disease Models, Animal ; Humans ; Kinetics ; Myocardial Infarction/blood ; Myocardial Infarction/diagnosis ; Swine ; Troponin I/blood ; Troponin T/blood
Chemical Substances	Biomarkers ; Carrier Proteins ; Troponin I ; Troponin T ; myosin-binding protein C
Language	English
Publishing date	2013-12-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00846.2013
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Article ; Online: Changes in miRNA expression in patients with peripheral arterial vascular disease during moderate- and vigorous-intensity physical activity.

Sieland, Johanna / Niederer, Daniel / Engeroff, Tobias / Vogt, Lutz / Troidl, Christian / Schmitz-Rixen, Thomas / Banzer, Winfried / Troidl, Kerstin

European journal of applied physiology

2022 Volume 123, Issue 3, Page(s) 645–654

Abstract: Background: Walking is the preferred therapy for peripheral arterial disease in early stage. An effect of walking exercise is the increase of blood flow and fluid shear stress, leading, triggered by arteriogenesis, to the formation of collateral blood ... ...

Abstract	Background: Walking is the preferred therapy for peripheral arterial disease in early stage. An effect of walking exercise is the increase of blood flow and fluid shear stress, leading, triggered by arteriogenesis, to the formation of collateral blood vessels. Circulating micro-RNA may act as an important information transmitter in this process. We investigated the acute effects of a single bout of 1) aerobic walking with moderate intensity; and 2) anaerobic walking with vigorous intensity on miRNA parameters related to vascular collateral formation. Methods: Ten (10) patients with peripheral arterial disease with claudication (age 72 ± 7 years) participated in this two-armed, randomized-balanced cross-over study. The intervention arms were single bouts of supervised walking training at (1) vigorous intensity on a treadmill up to volitional exhaustion and (2) moderate intensity with individual selected speed for a duration of 20 min. One week of washout was maintained between the arms. During each intervention, heart rate was continuously monitored. Acute effects on circulating miRNAs and lactate concentration were determined using pre- and post-intervention measurement comparisons. Results: Vigorous-intensity walking resulted in a higher heart rate (125 ± 21 bpm) than the moderate-intensity intervention (88 ± 9 bpm) (p < 0.05). Lactate concentration was increased after vigorous-intensity walking (p = 0.005; 3.3 ± 1.2 mmol/l), but not after moderate exercising (p > 0.05; 1.7 ± 0.6 mmol/l). The circulating levels of miR-142-5p and miR-424-5p were up-regulated after moderate-intensity (p < 0.05), but not after vigorous-intensity training (p > 0.05). Conclusion: Moderate-intensity walking seems to be more feasible than vigorous exercises to induce changes of blood flow and endurance training-related miRNAs in patients with peripheral arterial disease. Our data thus indicates that effect mechanisms might follow an optimal rather than a maximal dose response relation. Steady state walking without the necessity to reach exhaustion seems to be better suited as stimulus.
MeSH term(s)	Humans ; Aged ; MicroRNAs ; Cross-Over Studies ; Peripheral Arterial Disease ; Exercise Therapy ; Exercise ; Walking ; Lactates
Chemical Substances	MicroRNAs ; Lactates
Language	English
Publishing date	2022-11-23
Publishing country	Germany
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	124793-1
ISSN	1439-6327 ; 1432-1025 ; 0301-5548 ; 1439-6319
ISSN (online)	1439-6327 ; 1432-1025
ISSN	0301-5548 ; 1439-6319
DOI	10.1007/s00421-022-05091-2
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Article ; Online: Noninvasive sampling of the distal airspace via HME-filter fluid is not useful to detect SARS-CoV-2 in intubated patients.

Reifart, Joerg / Liebetrau, Christoph / Troidl, Christian / Madlener, Katharina / Rolf, Andreas

Critical care (London, England)

2021 Volume 25, Issue 1, Page(s) 126

MeSH term(s)	Aged ; Aged, 80 and over ; Air Microbiology ; COVID-19/therapy ; Environmental Monitoring/methods ; Female ; Filtration/instrumentation ; Humans ; Intubation/statistics & numerical data ; Male ; SARS-CoV-2/isolation & purification
Language	English
Publishing date	2021-03-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2041406-7
ISSN	1466-609X ; 1364-8535
ISSN (online)	1466-609X
ISSN	1364-8535
DOI	10.1186/s13054-021-03549-x
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Article ; Online: Effects of single bouts of different endurance exercises with different intensities on microRNA biomarkers with and without blood flow restriction: a three-arm, randomized crossover trial.

Sieland, Johanna / Niederer, Daniel / Engeroff, Tobias / Vogt, Lutz / Troidl, Christian / Schmitz-Rixen, Thomas / Banzer, Winfried / Troidl, Kerstin

European journal of applied physiology

2021 Volume 121, Issue 11, Page(s) 3243–3255

Abstract: Purpose: Physical activity is associated with altered levels of circulating microRNAs (ci-miRNAs). Changes in miRNA expression have great potential to modulate biological pathways of skeletal muscle hypertrophy and metabolism. This study was designed to ...

Abstract	Purpose: Physical activity is associated with altered levels of circulating microRNAs (ci-miRNAs). Changes in miRNA expression have great potential to modulate biological pathways of skeletal muscle hypertrophy and metabolism. This study was designed to determine whether the profile of ci-miRNAs is altered after different approaches of endurance exercise. Methods: Eighteen healthy volunteers (aged 24 ± 3 years) participated this three-arm, randomized-balanced crossover study. Each arm was a single bout of treadmill-based acute endurance exercise at (1) 100% of the individual anaerobic threshold (IANS), (2) at 80% of the IANS and (3) at 80% of the IANS with blood flow restriction (BFR). Load-associated outcomes (fatigue, feeling, heart rate, and exhaustion) as well as acute effects (circulating miRNA patterns and lactate) were determined. Results: All training interventions increased the lactate concentration (LC) and heart rate (HR) (p < 0.001). The high-intensity intervention (HI) resulted in a higher LC than both lower intensity protocols (p < 0.001). The low-intensity blood flow restriction (LI-BFR) protocol led to a higher HR and higher LC than the low-intensity (LI) protocol without BFR (p = 0.037 and p = 0.003). The level of miR-142-5p and miR-197-3p were up-regulated in both interventions without BFR (p < 0.05). After LI exercise, the expression of miR-342-3p was up-regulated (p = 0.038). In LI-BFR, the level of miR-342-3p and miR-424-5p was confirmed to be up-regulated (p < 0.05). Three miRNAs and LC show a significant negative correlation (miR-99a-5p, p = 0.011, r = - 0.343/miR-199a-3p, p = 0.045, r = - 0.274/miR-125b-5p, p = 0.026, r = - 0.302). Two partial correlations (intervention partialized) showed a systematic impact of the type of exercise (LI-BFR vs. HI) (miR-99a-59: r = - 0.280/miR-199a-3p: r = - 0.293). Conclusion: MiRNA expression patterns differ according to type of activity. We concluded that not only the intensity of the exercise (LC) is decisive for the release of circulating miRNAs-as essential is the type of training and the oxygen supply.
MeSH term(s)	Biomarkers/blood ; Blood Flow Restriction Therapy ; Cross-Over Studies ; Exercise/physiology ; Exercise Test ; Female ; Healthy Volunteers ; Heart Rate/physiology ; Humans ; Lactates/blood ; Male ; MicroRNAs/blood ; Young Adult
Chemical Substances	Biomarkers ; Lactates ; MicroRNAs
Language	English
Publishing date	2021-08-25
Publishing country	Germany
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	124793-1
ISSN	1439-6327 ; 1432-1025 ; 0301-5548 ; 1439-6319
ISSN (online)	1439-6327 ; 1432-1025
ISSN	0301-5548 ; 1439-6319
DOI	10.1007/s00421-021-04786-2
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Article: Material und Information! - Diskussionsforum zum Aufbau medizinischer Biobanken

Troidl, K. / Troidl, C. / Simon, F.

Gefässchirurgie

2018 Volume 23, Issue 8, Page(s) 608

Language	German
Document type	Article
ZDB-ID	1317513-0
ISSN	0948-7034
Database	Current Contents Medicine

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