Therapeutic modulation of RNA-binding protein Rbm38 facilitates re-endothelialization after arterial injury

Sonnenschein, Kristina; Fiedler, Jan; Pfanne, Angelika; Just, Annette; Mitzka, Saskia; Geffers, Robert; Pich, Andreas; Bauersachs, Johann; Thum, Thomas

doi:10.1093/cvr/cvz063

Cited by 13 publications

(9 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transfection experiments. As described before 38 , transient liposomal transfection of cells was performed at a confluence of 60-70% 1 day after seeding. Final concentration of oligonucleotides was 100 nM for siRNA.…”

Section: Measurement Of Biomarkersmentioning

confidence: 99%

Blood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy

Sonnenschein

Fiedler

Gonzalo-Calvo

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary heart diseases and can be classified into an obstructive (HOCM) and non-obstructive (HNCM) form. Major characteristics for HCM are the hypertrophy of cardiomyocytes and development of cardiac fibrosis. Patients with HCM have a higher risk for sudden cardiac death compared to a healthy population. In the present study, we investigated the abundancy of selected proteins as potential biomarkers in patients with HCM. We included 60 patients with HCM and 28 healthy controls and quantitatively measured the rate of a set of 92 proteins already known to be associated with cardiometabolic processes via protein screening using the proximity extension assay technology in a subgroup of these patients (20 HCM and 10 healthy controls). After validation of four hits in the whole cohort of patients consisting of 88 individuals (60 HCM patients, 28 healthy controls) we found only one candidate, c-KIT, which was regulated significantly different between HCM patients and healthy controls and thus was chosen for further analyses. c-KIT is a tyrosine-protein kinase acting as receptor for the stem cell factor and activating several pathways essential for cell proliferation and survival, hematopoiesis, gametogenesis and melanogenesis. Serum protein levels of c-KIT were significantly lower in patients with HCM than in healthy controls, even after adjusting for confounding factors age and sex. In addition, c-KIT levels in human cardiac tissue of patients with HOCM were significant higher compared to controls indicating high levels of c-KIT in fibrotic myocardium. Furthermore, c-KIT concentration in serum significantly correlated with left ventricular end-diastolic diameter in HOCM, but not HCM patients. The present data suggest c-KIT as a novel biomarker differentiating between patients with HCM and healthy population and might provide further functional insights into fibrosis-related processes of HOCM.

show abstract

Section: Measurement Of Biomarkersmentioning

confidence: 99%

Blood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy

Sonnenschein

Fiedler

Gonzalo-Calvo

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…LC-MS was performed as described previously (Sonnenschein et al, 2019). Briefly, the whole cell lysate total protein from replicative senescence VSMCs was used for immunoprecipitation and stained via the Coomassie solution for 45min at room temperature.…”

Section: Liquid Chromatography-masspectrometry (Lc-ms) and Bioinformamentioning

confidence: 99%

Inflammatory Drivers of Cardiovascular Disease: Molecular Characterization of Senescent Coronary Vascular Smooth Muscle Cells

et al. 2020

Self Cite

View full text Add to dashboard Cite

Stojanović et al. Vascular Smooth Muscle Cell Senescence deregulation to warrant senescent VSMC detection, we have conducted a non-biased proteomics and in silico analysis of RS VSMC demonstrating altered RNA biology as the central molecular feature of senescence in this cell type. Therefore, key proteins involved with RNA functionality, HMGB-1 release, LMNB-1 downregulation, in junction with nuclear enlargement, can be used as markers of VSMC senescence, enabling the detection of these pathogenic pro-inflammatory cells in future therapeutic studies in ischemic heart disease and atherosclerosis.

show abstract

“…This response network is also mediated through miR-223 and hypoxia inducible factor 1 alpha (HIF1A), both of which are important node regulators of vascular inflammatory response [48,49]. RNA-binding motif protein 38 (RBM38) has identified roles in endothelial repair following arterial injury [50] and deficient mouse models develop an accelerated aging phenotype and have impaired hematopoiesis [51].…”

Section: Plos Onementioning

confidence: 99%

The association between poverty and gene expression within peripheral blood mononuclear cells in a diverse Baltimore City cohort

et al. 2020

View full text Add to dashboard Cite

Socioeconomic status (SES), living in poverty, and other social determinants of health contribute to health disparities in the United States. African American (AA) men living below poverty in Baltimore City have a higher incidence of mortality when compared to either white males or AA females living below poverty. Previous studies in our laboratory and elsewhere suggest that environmental conditions are associated with differential gene expression (DGE) patterns in peripheral blood mononuclear cells (PBMCs). DGE have also been associated with hypertension and cardiovascular disease (CVD) and correlate with race and sex. However, no studies have investigated how poverty status associates with DGE between male and female AAs and whites living in Baltimore City. We examined DGE in 52 AA and white participants of the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) cohort, who were living above or below 125% of the 2004 federal poverty line at time of sample collection. We performed a microarray to assess DGE patterns in PBMCs from these participants. AA males and females living in poverty had the most genes differentially-expressed compared with above poverty controls. Gene ontology (GO) analysis identified unique and overlapping pathways related to the endosome, single-stranded RNA binding, long-chain fatty-acyl-CoA biosynthesis, toll-like receptor signaling, and others within AA males and females living in poverty and compared with their above poverty controls. We performed RT-qPCR to validate top differentially-expressed genes in AA males. We found that KLF6, DUSP2, RBM34, and CD19 are expressed at significantly lower levels in AA males in poverty and KCTD12 is higher compared to above poverty controls. This study serves as an additional link to better understand the gene expression response in peripheral blood mononuclear cells in those living in poverty.

show abstract

Therapeutic modulation of RNA-binding protein Rbm38 facilitates re-endothelialization after arterial injury

Cited by 13 publications

References 36 publications

Blood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy

Blood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy

Inflammatory Drivers of Cardiovascular Disease: Molecular Characterization of Senescent Coronary Vascular Smooth Muscle Cells

The association between poverty and gene expression within peripheral blood mononuclear cells in a diverse Baltimore City cohort

Contact Info

Product

Resources

About