Extracellular matrix remodeling in animal models of anthracycline-induced cardiomyopathy: a meta-analysis

Figures

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  Fig. 1. PRISMA flowchart of study inclusion in the systematic review. ECM=extracellular matrix

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  Fig. 2. Differentially expressed proteins and mRNAs from the random effects meta-analysis of studies in mice, rats, and rabbits with anthracycline-induced cardiomyopathy (ACMP). The x-axis indicates the log2 ratio of the means (ROM) from the random effects meta-analysis in ACMP compared to controls. Differentially expressed proteins and mRNAs (mR) with a ROM >1.2 or <0.83 and p-value <0.05 are shown. The size of each square is proportional with the number of studies in which the protein or mRNA was measured. Lines indicate the 95% confidence interval of the log2 ROM. MMP=matrix metalloproteinase, NTT=N-terminal truncated, TSP=thrombospondin, CTGF=connective tissue growth factor, TGFb1=transforming growth factor beta 1, SMAD=mothers against decapentaplegic homolog, p38 MAPK (p38 mitogen-activated protein kinases), pJAK2=phosphorylated janus kinase 2, BDNF=brain-derived neurotrophic factor, BMP=bone morphogenetic protein, mTOR=mechanistic target of rapamycin kinase, pAKT=phosphorylated protein kinase B, GAL3=galectin 3, LMO4=LIM domain transcription factor, TNFa=tumor necrosis factor alpha, IL=interleukin, NFkB=nuclear factor kappa B, NLRP3=NLR family pyrin domain containing 3,…

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  Fig. 3. Temporal expression patterns of extracellular matrix-related proteins in mouse, rat, and rabbit models of anthracycline-induced cardiomyopathy (ACMP). Every dot represents one study where the size is proportional to the weight in the meta-regression. Lines and ribbons represent the meta-regression fit and 95% confidence interval. Proteins significantly association with time after first anthracycline injection in the meta-regression were connective tissue growth factor (CTGF, negative association, p = 0.02), brain natriuretic peptide (BNP, positive association, p = 0.03) and matrix metalloproteinase 9 (MMP9, positive association, p = 0.04). ANP=atrial natriuretic peptide, MMP2=matrix metalloproteinase 2, mR=mRNA, NF-κB=nuclear factor-κB, TGFß=transforming growth factor beta, TNFα=tumor necrosis factor alpha, pAKT=phosphorylated protein kinase B, p38 MAPK=p38 mitogen-activated protein kinases

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  Fig. 4. Relationship between interstitial fibrosis area (A), systolic function (B), apoptosis (C), and time after first anthracycline injection in individual studies in mice, rats, and rabbits. Every dot represents one study where the size is proportional to the weight in the meta-regression. Lines and ribbons represent the meta-regression fit and 95% confidence interval, respectively. Interstitial fibrosis area, left ventricular (LV) systolic function (LV ejection fraction (LVEF) or fractional shortening (FS)), and apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)) were expressed as a standardized mean difference (SMD) between anthracycline-induced cardiomyopathy (ACMP) and control animals (calculated as the difference in means between ACMP animals and control animals divided by the standard deviation)

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  Fig. 5. Summary of extracellular matrix remodeling in anthracycline-induced cardiomyopathy. Upregulated markers are in red; downregulated markers are in blue. AKT=phosphorylated protein kinase B, ANT=anthracyclines, CTGF=connective tissue growth factor, MMP=matrix metalloproteinase, NF-κB=nuclear factor-κB, p38 MAPK=p38 mitogen-activated protein kinases, SMAD=Small Mothers Against Decapentaplegic homolog, TGFb=transforming growth factor ß, TIMP=tissue inhibitor of metalloproteinase, TNF=tumor necrosis factor, TSP2=thrombospondin 2. Created with biorender.com