Genetic Deletion of Galectin-3 Alters the Temporal Evolution of Macrophage Infiltration and Healing Affecting the Cardiac Remodeling and Function after Myocardial Infarction in Mice

Purpose. Myocardial regeneration is one of the most ambitious goals in prevention of adverse cardiac remodeling. Macrophages play a key role in transition from inflammatory to regenerative phase during wound healing following myocardial infarction (MI). We have accumulated data on macrophage properties ex vivo and in cell culture. However, there is no clear information about phenotypic heterogeneity of cardiac macrophages in patients with MI. The purpose of the project was to assess cardiac macrophage infiltration during wound healing following myocardial infarction in clinical settings taking into consideration experimental knowledge.Material and Methods. The study included 41 patients with fatal MI type 1. In addition to routine analysis, macrophages infiltration was assessed by immunohistochemistry. We used CD68 as a marker for the cells of the macrophage lineage, while CD163, CD206, and stabilin-1 were considered as M2 macrophage biomarkers. Nine patients who died from noncardiovascular causes comprised the control group.Results. The intensity of cardiac macrophage infiltration was higher during the regenerative phase than during the inflammatory phase. Results of immunohistochemical analysis demonstrated the presence of phenotypic heterogeneity of cardiac macrophages in patients with MI. We noticed that numbers of CD68+, CD163+, CD206+, and stabilin-1+ macrophages depended on MI phase.Conclusion. Our study supports prospects for implementation of macrophage phenotyping in clinic practice. Improved understanding of phenotypic heterogeneity might become the basis of a method to predict adverse cardiac remodeling and the first step in developing myocardial regeneration target therapy.

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An Elastic, Biodegradable Cardiac Patch Induces Contractile Smooth Muscle and Improves Cardiac Remodeling and Function in Subacute Myocardial Infarction

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2007.02.050 ◽

2007 ◽

Vol 49 (23) ◽

pp. 2292-2300 ◽

Cited By ~ 156

Author(s):

Kazuro L. Fujimoto ◽

Kimimasa Tobita ◽

W. David Merryman ◽

Jianjun Guan ◽

Nobuo Momoi ◽

...

Keyword(s):

Myocardial Infarction ◽

Smooth Muscle ◽

Cardiac Remodeling ◽

And Function ◽

Cardiac Patch

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Contrast Enhanced Echocardiographic Follow-up of Cardiac Remodeling and Function after Myocardial Infarction in Rats

Ultrasound in Medicine & Biology ◽

10.1016/j.ultrasmedbio.2007.04.016 ◽

2007 ◽

Vol 33 (10) ◽

pp. 1561-1571 ◽

Cited By ~ 2

Author(s):

Steffen Rabald ◽

Andreas Hagendorff ◽

Dietrich Pfeiffer ◽

Heinz-Gerd Zimmer ◽

Alexander Deten

Keyword(s):

Myocardial Infarction ◽

Cardiac Remodeling ◽

Contrast Enhanced ◽

And Function

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P305By promoting cardiac regeneration FGF10 preserves cardiac remodeling and function after myocardial infarction

Cardiovascular Research ◽

10.1093/cvr/cvy060.222 ◽

2018 ◽

Vol 114 (suppl_1) ◽

pp. S78-S78

Author(s):

S Payan ◽

F Hubert ◽

R Sturny ◽

R G Kelly ◽

F Rochais

Keyword(s):

Myocardial Infarction ◽

Cardiac Remodeling ◽

Cardiac Regeneration ◽

And Function

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Galectin-3 and post-myocardial infarction cardiac remodeling

European Journal of Pharmacology ◽

10.1016/j.ejphar.2015.06.025 ◽

2015 ◽

Vol 763 ◽

pp. 115-121 ◽

Cited By ~ 34

Author(s):

Wouter C. Meijers ◽

A. Rogier van der Velde ◽

Domingo A. Pascual-Figal ◽

Rudolf A. de Boer

Keyword(s):

Myocardial Infarction ◽

Cardiac Remodeling ◽

Post Myocardial Infarction ◽

Galectin 3

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Podoplanin neutralization improves cardiac remodeling and function after myocardial infarction

JCI Insight ◽

10.1172/jci.insight.126967 ◽

2019 ◽

Vol 4 (15) ◽

Cited By ~ 3

Author(s):

Maria Cimini ◽

Venkata Naga Srikanth Garikipati ◽

Claudio de Lucia ◽

Zhongjian Cheng ◽

Chunlin Wang ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Remodeling ◽

And Function

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Interleukin-1α dependent survival of cardiac fibroblasts is associated with StAR/STARD1 expression and improved cardiac remodeling and function after myocardial infarction

Journal of Molecular and Cellular Cardiology ◽

10.1016/j.yjmcc.2020.10.013 ◽

2020 ◽

Author(s):

Talya Razin ◽

Naomi Melamed-Book ◽

Jasmin Argaman ◽

Iris Galin ◽

Yosef Lowy ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Remodeling ◽

Cardiac Fibroblasts ◽

Interleukin 1Α ◽

And Function

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Increased syndecan expression following myocardial infarction indicates a role in cardiac remodeling

Physiological Genomics ◽

10.1152/physiolgenomics.00144.2002 ◽

2004 ◽

Vol 16 (3) ◽

pp. 301-308 ◽

Cited By ~ 30

Author(s):

Alexandra Vanessa Finsen ◽

Per Reidar Woldbaek ◽

Jian Li ◽

Jiaping Wu ◽

Torstein Lyberg ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Remodeling ◽

Wilms Tumor ◽

Northern Blotting ◽

Left Ventricular ◽

Fgf Receptor ◽

Protein Levels ◽

Primary Surgery ◽

Ventricular Tissue ◽

And Function

Finsen, Alexandra Vanessa, Per Reidar Woldbaek, Jian Li, Jiaping Wu, Torstein Lyberg, Theis Tonnessen, and Geir Christensen. Increased syndecan expression following myocardial infarction indicates a role in cardiac remodeling. Physiol Genomics 16: 301-308, 2004. First published November 18, 2003; 10.1152/physi-olgenomics. 00144.2002.—The purpose of this study was to identify essential genes involved in myocardial growth and remodeling following myocardial infarction (MI). Left ventricular noninfarcted tissues from six mice subjected to MI under general anesthesia and from six sham-operated mice were obtained 1 wk after primary surgery and analyzed by means of cDNA filter arrays. Out of a total of 1,176 genes, 641 were consistently expressed, twenty-three were upregulated and thirteen downregulated. Five genes were only expressed following MI. Syndecan-3, a transmembranous heparan sulfate proteoglycan, was found to be upregulated together with a transcriptional activator of syndecans, Wilms tumor protein 1 (WT-1). Northern blotting demonstrated a significant upregulation of syndecan-1, -2, -3, and -4, WT-1, fibronectin, and basic fibroblast growth factor (FGF) receptor 1. Furthermore, Western blot analysis showed statistically significant increases in protein levels for syndecan-3 and -4. In conclusion, we have identified a subset of genes with increased expression in noninfarcted left ventricular tissue following MI, including syndecans 1–4, WT-1, fibronectin, collagen 6A, and FGF receptor 1. Since the syndecans link the cytoskeleton to the extracellular matrix and function as required coreceptors for FGF, we suggest a role for the syndecans in cardiac remodeling following MI.

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Serum and Echocardiographic Markers May Synergistically Predict Adverse Cardiac Remodeling after ST-Segment Elevation Myocardial Infarction in Patients with Preserved Ejection Fraction

Diagnostics ◽

10.3390/diagnostics10050301 ◽

2020 ◽

Vol 10 (5) ◽

pp. 301

Author(s):

Tamara Pecherina ◽

Anton Kutikhin ◽

Vasily Kashtalap ◽

Victoria Karetnikova ◽

Olga Gruzdeva ◽

...

Keyword(s):

Myocardial Infarction ◽

Ejection Fraction ◽

Cardiac Remodeling ◽

Left Ventricular ◽

Serum Biomarkers ◽

St Segment Elevation ◽

Segment Elevation Myocardial Infarction ◽

St Segment ◽

Galectin 3 ◽

Echocardiographic Parameters

Improvement of risk scoring is particularly important for patients with preserved left ventricular ejection fraction (LVEF) who generally lack efficient monitoring of progressing heart failure. Here, we evaluated whether the combination of serum biomarkers and echocardiographic parameters may be useful to predict the remodeling-related outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and preserved LVEF (HFpEF) as compared to those with reduced LVEF (HFrEF). Echocardiographic assessment and measurement of the serum levels of NT-proBNP, sST2, galectin-3, matrix metalloproteinases, and their inhibitors (MMP-1, MMP-2, MMP-3, TIMP-1) was performed at the time of admission (1st day) and on the 10th–12th day upon STEMI onset. We found a reduction in NT-proBNP, sST2, galectin-3, and TIMP-1 in both patient categories from hospital admission to the discharge, as well as numerous correlations between the indicated biomarkers and echocardiographic parameters, testifying to the ongoing ventricular remodeling. In patients with HFpEF, NT-proBNP, sST2, galectin-3, and MMP-3 correlated with the parameters reflecting the diastolic dysfunction, while in patients with HFrEF, these markers were mainly associated with LVEF and left ventricular end-systolic volume/diameter. Therefore, the combination of the mentioned serum biomarkers and echocardiographic parameters might be useful for the prediction of adverse cardiac remodeling in patients with HFpEF.

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miR155 Deficiency Reduces Myofibroblast Density but Fails to Improve Cardiac Function after Myocardial Infarction in Dyslipidemic Mouse Model

International Journal of Molecular Sciences ◽

10.3390/ijms22115480 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5480

Author(s):

David Schumacher ◽

Adelina Curaj ◽

Sakine Simsekyilmaz ◽

Andreas Schober ◽

Elisa A. Liehn ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Mouse Model ◽

Cardiac Remodeling ◽

Left Ventricular ◽

Cardiomyocyte Hypertrophy ◽

Cardiac Inflammation ◽

Infarction Size ◽

Adverse Remodeling ◽

And Function

Myocardial infarction remains the most common cause of heart failure with adverse remodeling. MicroRNA (miR)155 is upregulated following myocardial infarction and represents a relevant regulatory factor for cardiac remodeling by engagement in cardiac inflammation, fibrosis and cardiomyocyte hypertrophy. Here, we investigated the role of miR155 in cardiac remodeling and dysfunction following myocardial infarction in a dyslipidemic mouse model. Myocardial infarction was induced in dyslipidemic apolipoprotein E-deficient (ApoE−/−) mice with and without additional miR155 knockout by ligation of the LAD. Four weeks later, echocardiography was performed to assess left ventricular (LV) dimensions and function, and mice were subsequently sacrificed for histological analysis. Echocardiography revealed no difference in LV ejection fractions, LV mass and LV volumes between ApoE−/− and ApoE−/−/miR155−/− mice. Histology confirmed comparable infarction size and unaltered neoangiogenesis in the myocardial scar. Notably, myofibroblast density was significantly decreased in ApoE−/−/miR155−/− mice compared to the control, but no difference was observed for total collagen deposition. Our findings reveal that genetic depletion of miR155 in a dyslipidemic mouse model of myocardial infarction does not reduce infarction size and consecutive heart failure but does decrease myofibroblast density in the post-ischemic scar.

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