1. Blood speaks: Personalised medicine profiling for heart failure patients
- Author
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Mark A. Sussman and Fareheh Firouzi
- 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 - 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, Graphical abstract Image, graphical abstract
- Published
- 2020