A5046556211- Cardiomyopathy and Myosin Studies
- Cardiovascular Effects of Exercise
- Viral Infections and Immunology Research
- Congenital heart defects research
- Muscle Physiology and Disorders
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Trypanosoma species research and implications
- Wnt/β-catenin signaling in development and cancer
- Cardiovascular Function and Risk Factors
- Tissue Engineering and Regenerative Medicine
- Cardiac Fibrosis and Remodeling
- Pancreatic function and diabetes
- Bone Metabolism and Diseases
- Health Promotion and Cardiovascular Prevention
- Cardiac electrophysiology and arrhythmias
- Biochemical Acid Research Studies
- Cancer-related gene regulation
- Genetics and Neurodevelopmental Disorders
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Renal cell carcinoma treatment
- Pediatric health and respiratory diseases
- Bone health and treatments
- Chronic Disease Management Strategies
- School Health and Nursing Education
- Protease and Inhibitor Mechanisms
AstraZeneca (Germany)
2020-2023
University Medical Center Hamburg-Eppendorf
2011-2021
Universität Hamburg
2011-2021
German Centre for Cardiovascular Research
2012-2021
University of Rostock
2021
AstraZeneca (Brazil)
2021
Committee on Publication Ethics
2018
Martini-Klinik
2014
Inserm
2012
Institut de Myologie
2012
Hypertrophic cardiomyopathy (HCM) is characterized by asymmetric left ventricular hypertrophy, diastolic dysfunction and myocardial disarray. HCM caused mutations in sarcomeric genes, but >40% of patients, the mutation not yet identified. We hypothesized that FHL1, encoding four-and-a-half-LIM domains 1, could be another disease gene since it has been shown to cause distinct myopathies, sometimes associated with cardiomyopathy. evaluated 121 devoid a known genes. identified three novel...
Hypertrophic cardiomyopathy (HCM) is a cardiac genetic disease accompanied by structural and contractile alterations. We identified rare c.740C>T (p.T247M) mutation in ACTN2, encoding α-actinin 2 HCM patient, who presented with left ventricular hypertrophy, outflow tract obstruction, atrial fibrillation. generated patient-derived human-induced pluripotent stem cells (hiPSCs) show that hiPSC-derived cardiomyocytes engineered heart tissues recapitulated several hallmarks of HCM, such as...
Although Wnt signaling in osteoblasts is of critical importance for the regulation bone remodeling, it not yet known which specific receptors Frizzled family are functionally relevant this process. In paper, we show that Fzd9 induced upon osteoblast differentiation and Fzd9−/− mice display low mass caused by impaired formation. Our analysis primary demonstrated defects matrix mineralization spite normal expression established markers. contrast, observed a reduced chemokines...
The transcription factor Islet-1 is a marker of cardiovascular progenitors during embryogenesis. isolation Islet-1-positive (Islet-1(+)) cells from early postnatal hearts suggested that also marks cardiac in adult life.
Contraction and relaxation are fundamental aspects of cardiomyocyte functional biology. They reflect the response contractile machinery to systolic increase diastolic decrease cytoplasmic Ca(2+) concentration. The analysis function transients is therefore important discriminate between myofilament responsiveness changes in homeostasis. This article describes an automated technology perform sequential force up 11 strip-format, fibrin-based rat, mouse, human fura-2-loaded engineered heart...
Myosin-binding protein C (Mybpc3)-targeted knock-in mice (KI) recapitulate typical aspects of human hypertrophic cardiomyopathy. We evaluated whether these functional alterations can be reproduced in engineered heart tissue (EHT) and yield novel mechanistic information on the function cMyBP-C. EHTs were generated from cardiac cells neonatal KI, heterozygous (HET) or wild-type controls (WT) developed without apparent morphological differences. KI had 70% HET 20% lower total cMyBP-C levels...
Based on evidence that FHL2 (four and a half LIM domains protein 2) negatively regulates cardiac hypertrophy we tested whether altered expression or variants could be associated with hypertrophic cardiomyopathy (HCM). HCM is myocardial disease characterized by left ventricular hypertrophy, diastolic dysfunction increased interstitial fibrosis mainly caused mutations in genes coding for sarcomeric proteins. mRNA level, level I-band-binding density were lower patients than control individuals....
Wnt signalling is a key pathway controlling bone formation in mice and humans. One of the regulators this Dkk1, which antagonizes through ternary complex with transmembrane receptors Krm1/2 Lrp5/6, thereby blocking induction by latter ones. Here we show that Kremen-2 (Krm2) predominantly expressed bone, its osteoblast-specific over-expression transgenic (Col1a1-Krm2) results severe osteoporosis. Histomorphometric analysis revealed osteoblast maturation are disturbed Col1a1-Krm2 mice, whereas...
Hypertrophic cardiomyopathy (HCM) is often accompanied by increased myofilament Ca2+ sensitivity and diastolic dysfunction. Recent findings indicate late Na+ current density in human HCM cardiomyocytes. Since ranolazine has the potential to decrease current, we investigated its effects an Mybpc3-targeted knock-in (KI) mouse model of HCM. Unloaded sarcomere shortening transients were measured KI wild-type (WT) Measurements performed at baseline (1 Hz) under workload (30 nM isoprenaline (ISO),...
Recent studies evaluating the predictive value of different variables on future exacerbations suggest exacerbation history as strongest predictor. We examined effect subsequent events in a large sample population with over 250,000 COPD patients using up to 8 years longitudinal healthcare data from Germany.
Familial hypertrophic cardiomyopathy (FHC) is caused by mutations in genes encoding sarcomeric proteins. Incomplete penetrance suggests the existence of modifier genes. Calmodulin (CaM) could be importance given key role Ca2+ for cardiac contractile function and growth. Any variant that affects CaM expression and/or may impact on FHC clinical expression. We screened promoter region human calmodulin III gene (CALM3) identified a new −34T>A polymorphism with T-allele frequency 0.70. The...
Islet-1 expression identifies populations of progenitor cells in embryonic, fetal, and newborn murine hearts that are able to give rise all cardiac cell lineages ex vivo vivo. Using systematic immunohistochemistry, we investigated whether islet-1-positive present adult mouse heart from the perspective their potential therapeutic utility. The presence, localization, nature were assessed mice different strains, ages, conditions. Islet-1-positive postnatal day 1 young adulthood. Depending on...
Cardiomyopathies are categorized as extrinsic, being caused by external factors, such hypertension, ischemia, inflammation, valvular dysfunction, or intrinsic, which correspond to myocardial diseases without identifiable causes. These so called primary cardiomyopathies can be in four main forms: hypertrophic, dilated, restrictive, and arrhythmogenic right ventricular cardiomyopathy. diagnosed clinical expression, echocardiography, electrocardiography, non-invasive imaging, sometimes cardiac...
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac illness and can lead to diastolic dysfunction, sudden death heart failure. Treatment of HCM patients empirical current pharmacological treatments are unable stop disease progression or reverse hypertrophy. In this study, we tested if non-dihydropyridine Ca2+ channel blocker diltiazem, which previously showed potential progression, improve phenotype a mouse model (Mybpc3-targeted knock-in), based on mutation commonly found...
Background. Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac muscle disease with left ventricular hypertrophy, interstitial fibrosis and diastolic dysfunction. Increased myofilament Ca2+ sensitivity could be underlying cause of Epigallocatechin-3-gallate (EGCg), a catechin found in green tea has, been reported to decrease HCM models troponin mutations. However, whether this also case for HCM-associated thick filament mutations not known. Therefore, we evaluated EGCg...
Abstract Phosphorylation of cardiac myosin-binding protein C (cMyBP-C), encoded by MYBPC3 , increases the availability myosin heads for interaction with actin thus enhancing contraction. cMyBP-C phosphorylation level is lower in septal myectomies patients hypertrophic cardiomyopathy (HCM) than non-failing hearts. Here we compared effect phosphomimetic (D282) and wild-type (S282) gene transfer on HCM phenotype engineered heart tissues (EHTs) generated from a mouse model carrying Mybpc3...
Abstract Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease and caused by genetic variants that often increase sarcomeric Ca 2+ sensitivity. While sensitization explains diastolic dysfunction, genesis of ventricular arrhythmias unresolved. Here, we show HCM mutations or pharmacological interventions myofilament sensitivity generate bioenergetic mismatch oxidative stress during β-adrenergic stimulation which provide a trigger substrate for arrhythmias. For any...
Sulforaphane (SFN) is a phytochemical compound extracted from cruciferous plants, like broccoli or cauliflower. Its isothiocyanate group renders SFN reactive, thus allowing post-translational modification of cellular proteins to regulate their function with the potential for biological and therapeutic actions. stabilized variants recently received regulatory approval clinical studies in humans treatment neurological disorders cancer. Potential unwanted side effects on heart have not been...
Background. Hypertrophic cardiomyopathy (HCM) patients often present with diastolic dysfunction and a normal to supranormal systolic function. To counteract this hypercontractility, guideline therapies advocate treatment beta-adrenoceptor Ca2+ channel blockers. One well established pathomechanism for the hypercontractile phenotype frequently observed in HCM several mouse models is an increased myofilament sensitivity. Nebivolol, commonly used antagonist, has been reported lower maximal force...