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Blood speaks: Personalised medicine profiling for heart failure patients
- Source :
- EBioMedicine, EBioMedicine, Vol 58, Iss, Pp 102900-(2020)
- Publication Year :
- 2020
-
Abstract
- Background Bone marrow stem cell clonal dysfunction by somatic mutation is suspected to affect post-infarction myocardial regeneration after coronary bypass surgery (CABG). Methods Transcriptome and variant expression analysis was studied in the phase 3 PERFECT trial post myocardial infarction CABG and CD133+ bone marrow derived hematopoetic stem cells showing difference in left ventricular ejection fraction (∆LVEF) myocardial regeneration Responders (n=14; ∆LVEF +16% day 180/0) and Non-responders (n=9; ∆LVEF -1.1% day 180/0). Subsequently, the findings have been validated in an independent patient cohort (n=14) as well as in two preclinical mouse models investigating SH2B3/LNK antisense or knockout deficient conditions. Findings 1. Clinical: R differed from NR in a total of 161 genes in differential expression (n=23, q<br />Graphical abstract Image, graphical abstract
- Subjects :
- WT, wild type
Research paper
CSC, cardiac stem cell
EPOR, Erythropoietin receptor
LAD, Left anterior descending coronary artery, RIVA
Ang-1, Angiopoeitin 1
Clonal hematopoiesis of indeterminate pathology
Angiogenesis induction
MNC, Mononuclear cells
SH2B3, LNK [Src homology 2-B3 (SH2B3)] belongs to a family of SH2-containing proteins with important adaptor functions
Coronary bypass surgery
Profiling (information science)
CABG
CHIP, Clonal hematopoiesis of indeterminate potential
PI3K, Phosphoinositide-3-Kinase
m, mouse
BM, Bone marrow
PPMC, Pearson Product Moment Correlation
CHIP
BrdU, Brome deoxyuridine
NR, non-responder
IGF-1, Insuline-like Growth Factor 1
AUC, Area under curve
BMMNC, Bone marrow mononuclear cell
General Medicine
KSL, mouse bone marrow stem cell subpopulation c-KIT+ Sca-I+ lin
EGF, Epidermal growth factor
GFP, Green fluorescent protein
Public Health and Health Services
MI, myocardial infarction
lcsh:Medicine (General)
NGS, Next Generation Sequencing
medicine.medical_specialty
2019-20 coronavirus outbreak
Clinical Sciences
6MWT, 6-Minute Walk Test
InDel, mutation insertion or deletion variant
General Biochemistry, Genetics and Molecular Biology
CLARA, Clustering for Large Applications
PDFR, Platelet derived growth factor receptor
c-KIT/CD117, Stem Cell Factor Receptor c-KIT, CD117
HR, Hazard ratio
IGFBP, Insuline-like growth factor binding proteine
IHG, Analysis performed in accordance with ISHAGE guidelines
RFI, Reactome functional interaction
Machine learning
Humans
LAS, Longitudinal axis strain
Intensive care medicine
DE, Differential gene expression
Heart Failure
GWAS, Genome wide association study
CI, Confidence interval
hu, human
R, responder
lcsh:R
Myocardial regeneration
FACS, Fluorescence activated cell sorter
DNAseq, desoxyribonucleid acid sequencing
SNP, Single nucleotide polymorphism, variant
RT-PCR, Reverse transcriptase polymerase chain reaction
medicine.disease
Cardiac stem cell therapy
GMP, Good Manufacturing Practice
Post myocardial infarction heart failure
SDF-1, Stromal Cell-derived Factor 1
FDR, False discovery rate
PDGF, Platelet derived growth factor
EPO, Erythropoietin
MRI, Magnetic resonance imaging
VEGFR, Vascular Endothelial Growth Factor Receptor
AUR, Arch user repository
LCRC, Loss of cardiac regeneration capacity
GADPH, Glyceraldehyde 3 phosphate dehydrogenase
lcsh:Medicine
LVESD, Left Ventricular End Systolic Dimension
VCA, Virus-Capsid-Antigen
CEC, Circulating endothelial cells, CEC panel, CDs measured in PB
RNASeq, Ribonucleid acid sequencing
SUSAR, Suspected Unexpected Serious Adverse Reaction
GATA4, Transcriptional activator that binds to the consensus sequence 5′-AGATAG-3’
IL, Interleukin
Precision Medicine
CAP-EPC, Concentrated Ambient Particles – Endothelial Progenitor Cells
lcsh:R5-920
VEGF, Vascular Endothelial Growth Factor
SH2B3
STEMI, ST- segment Elevation Infarction
CD, Cluster of Differentiation
SCF, Stem Cell Factor
PBMNC, Peripheral blood mononuclear cell
CABG, Coronary Artery Bypass Graft
HSC, Hemopoeitic stem cell
ML, Machine learning
CFU, Colony-forming unit
PBMNC, mononuclear cells isolated from peripheral blood
LNK, SH2B adapter protein 3 (lymphocyte adapter protein)
Coronavirus disease 2019 (COVID-19)
BMSC, Bone marrow stem cells
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
LVEDV, Left Ventricular End Diastolic Volume
RWMS, Regional wall motion score
qPCR, Quantitative polymerase chain reaction
ROC, Receiver operating characteristics
CPC, cardiac progenitor cell
medicine
EGFR, Epidermal growth factor receptor
ICH GCP, Tripartite Guidelines Guideline for Good Clinical Practice
TiCoNE, Time course network enrichment
ELISA, Enzyme-Linked Immunosorbent Assay
PEI, Paul-Ehrlich Institute
LVEF, Left Ventricular Ejection Fraction
business.industry
HIF, Hypoxia-Inducible Factor, transcription factor
PB, Peripheral blood
EPC, Endothelial Progenitor Cells, EPC panel, CDs measured in PB
t-SNE, t-distributed stochastic neighbour embedding
ANCOVA, Analysis of covariance
WGCNA, Weighted gene coexpression network analysis
Heart failure
TNF, Tumor Necrosis Factor
PCR, Polymerase chain reaction
business
Subjects
Details
- ISSN :
- 23523964
- Volume :
- 58
- Database :
- OpenAIRE
- Journal :
- EBioMedicine
- Accession number :
- edsair.doi.dedup.....9bec689472e48af1a08ab0b6c96a33df