PHENOTYPIC HETEROGENEITY OF CARDIAC MACROPHAGES  DURING WOUND HEALING FOLLOWING MYOCARDIAL INFARCTION:  PERSPECTIVES IN CLINICAL RESEARCH

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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Stabilin-1+/SMA- macrophages in diagnostics of postinfarction tissue inflammation associated with adverse cardiac remodeling in patients with myocardial infarction

European Heart Journal ◽

10.1093/ehjci/ehaa946.0917 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Gombozhapova ◽

Y Rogovskaya ◽

M Rebenkova ◽

J Kzhyshkowska ◽

V Ryabov

Keyword(s):

Myocardial Infarction ◽

Cardiac Remodeling ◽

Smooth Muscle Actin ◽

Width Ratio ◽

Tissue Samples ◽

Tissue Inflammation ◽

Analysis Group ◽

Inflammatory Phase ◽

Amount Of Knowledge ◽

Regenerative Phase

Abstract Introduction Molecular biomarkers of monocytes/macrophages identified to date have provided advanced diagnostic capabilities. We have accumulated a large amount of knowledge related to the role of innate immune response in the development of postinfarction cardiac remodeling. However, there is no significant advancement in clinical studies. Purpose The purpose was to assess prospects of macrophage biomarkers in diagnostics of postinfarction tissue inflammation associated with adverse cardiac remodeling in patients with myocardial infarction (MI). Methods The study included 41 patients with MI type 1, died in 2013–2014. We used a biobank of tissue samples for analysis. Group 1 (n=24) comprised patients who died within 72 hours of MI (the inflammatory phase), group 2 (n=17) comprised patients who died 4–28 days after MI (the regenerative phase). Macrophage infiltration in the heart was assessed by double immunofluorescence. We used stabilin-1 as a marker of M2 macrophages, while α-smooth muscle actin (α-SMA) was considered as a marker of cell transdifferentiation. Cells were counted in the infarct (IA) and non-infarct area (NIA). Morphological determination of adverse cardiac remodeling was based on the ratio of heart size, in particular, length/width ratio that was <1.1. Results We identified subpopulations of stabilin-1+/α-SMA− and stabilin-1+/α-SMA+ macrophages. In the IA the number of stabilin-1+/α-SMA− macrophages was lower during the inflammatory phase than during the regenerative phase (Table 1). The calculation of sensitivity and specificity of stabilin-1+/α-SMA− macrophages in the NIA for predicting of adverse cardiac remodeling has shown following: AUC=0.96, p<0.001. The cut-off value was 18 cells/mm2. The ROC curve is presented in Figure 1. Conclusions We identified that number of stabilin-1+/α-SMA− macrophages in the NIA ranged from 0 to 18 cells/mm2 was associated with adverse cardiac remodeling. The presence of stabilin-1+/α-SMA+ macrophages could indicate persistent tissue inflammation and possibility of macrophage transdifferentiation and plasticity. Our study supports prospects for implementation of macrophage biomarkers in clinical practice that might become a breakthrough in the development of new methods for management of MI and following complications. Figure 1 Funding Acknowledgement Type of funding source: None

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Nucleolin Improves Heart Function During Recovery From Myocardial Infarction by Modulating Macrophage Polarization

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248421989570 ◽

2021 ◽

pp. 107424842198957

Author(s):

Yuting Tang ◽

Xiaofang Lin ◽

Cheng Chen ◽

Zhongyi Tong ◽

Hui Sun ◽

...

Keyword(s):

Myocardial Infarction ◽

Early Phase ◽

Heart Function ◽

Macrophage Polarization ◽

Late Phase ◽

Macrophage Infiltration ◽

Enzyme Linked Immunosorbent Assay ◽

M2 Macrophage ◽

M2 Macrophage Polarization ◽

Nucleolin Expression

Background: Nucleolin has multiple functions within cell survival and proliferation pathways. Our previous studies have revealed that nucleolin can significantly reduce myocardial ischemia-reperfusion injury by promoting myocardial angiogenesis and reducing myocardial apoptosis. In this study, we attempted to determine the role of nucleolin in myocardial infarction (MI) injury recovery and the underlying mechanism. Methods: Male BALB/c mice aged 6–8 weeks were used to set up MI models by ligating the left anterior descending coronary artery. Nucleolin expression in the heart was downregulated by intramyocardial injection of a lentiviral vector expressing nucleolin-specific small interfering RNA. Macrophage infiltration and polarization were measured by real-time polymerase chain reaction, flow cytometry, and immunofluorescence. Cytokines were detected by enzyme-linked immunosorbent assay. Results: Nucleolin expression in myocardium after MI induction decreased a lot at early phase and elevated at late phase. Nucleolin knockdown impaired heart systolic and diastolic functions and decreased the survival rate after MI. Macrophage infiltration increased in the myocardium after MI. Most macrophages belonged to the M1 phenotype at early phase (2 days) and the M2 phenotype increased greatly at late phase after MI. Nucleolin knockdown in the myocardium led to a decrease in M2 macrophage polarization with no effect on macrophage infiltration after MI. Furthermore, Notch3 and STAT6, key regulators of M2 macrophage polarization, were upregulated by nucleolin in RAW 264.7 macrophages. Conclusions: Lack of nucleolin impaired heart function during recovery after MI by reducing M2 macrophage polarization. This finding probably points to a new therapeutic option for ischemic heart disease.

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Production of vegetable oil blends and structured lipids and their effect on wound healing

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502015000200019 ◽

2015 ◽

Vol 51 (2) ◽

pp. 415-427 ◽

Cited By ~ 5

Author(s):

Juliana Neves Rodrigues Ract ◽

Fabiana Andreia Schäfer De Martini Soares ◽

Hosana Gomes Rodrigues ◽

José Ricardo Bortolon ◽

Gilson Masahiro Murata ◽

...

Keyword(s):

Wound Healing ◽

Healing Process ◽

Structured Lipids ◽

Physiological Saline ◽

Structured Lipid ◽

Control Group ◽

Wound Healing Process ◽

Oil Blends ◽

Inflammatory Phase ◽

Canola Oils

<p>Two oil blends (sunflower/canola oils 85/15 (BL1) and canola/linseed oils 70/30 (BL2)), were prepared and enzymatically interesterified to be applied to surgically-induced wounds in rats. Following surgery, the animals were submitted to the Treatment with Physiological Saline (TPS) (control group), Blends (TBL), and Structured Lipids (TSL). The control group (TPS) received physiological saline solution for 15 days. In TBL, BL1 was administered during the inflammation phase (days 0-3) and BL2 in the tissue formation and remodeling phase (days 4-15). In TSL, Structured Lipid 1 (SL1) and Structured Lipid 2 (SL2) were used instead of BL1 and BL2, respectively. The aim of this study was to compare wound closure evolution among rats treated with the blends or structured lipids versus control rats treated with physiological saline. The wound healing process was evaluated by measuring the wound areas along the treatments and the concentrations of cytokines. An increase in the areas of wounds treated with the blends and structured lipids in the inflammatory phase was observed, followed by a steeper closure curve compared to wounds treated with physiological saline. The changes observed during the inflammatory phase suggest a potential therapeutic application in cutaneous wound healing which should be further investigated.</p>

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Efektivitas Gel Ekstrak Bawang Putih terhadap Proses Penyembuhan Luka Fase Inflamasi

Jurnal Vokasi Kesehatan ◽

10.30602/jvk.v4i2.159 ◽

2018 ◽

Vol 4 (2) ◽

pp. 109

Author(s):

Mufimah Mufimah ◽

Uti Rusdian Hidayat ◽

Ichsan Budiharto

Keyword(s):

Wound Healing ◽

Wound Care ◽

Healing Process ◽

Garlic Extract ◽

Group Method ◽

Control Group ◽

Wound Healing Process ◽

Protection Mechanism ◽

Inflammatory Phase ◽

Post Test

Abstract: Efectiveness Gel Extract Of White On The Process Of Healing Inflamation Phase Heating. The inflammatory phase is a favorable body response as a protection mechanism. In the process of wound healing becomes a very important phase. Management of inflammation that is often used Non-Steroid Anti-Inflammatory class of salicylates on the skin that have side effects. The content of allicin in garlic can be used for problems that begin with the inflammatory phase. The use of gel from garlic extract is also easier to use and easier to clean. The study aim to determine the effectiveness of garlic extract gel to process wound inflammatory phase healing. This research is an experimental research with pre and post test with control group method with 24 samples. Conducted injury to the back area of rat length of wound 1 cm, depth to dermis. Conducted wound care, given gel extract of garlic concentration of 20%, 40%, 80% of the control using 0.9% NaCl compress. Using Kruskal Wallis test and Anova oneway showed concentration of 20%, 40%, and 80% of sig <0,05 ie 0.00. It was concluded that 20%, 40%, 80% garlic extract gel was effective against inflammatory wound healing process. The use of garlic extract gel is more effective in the wound inflammatory wound healing process.Abstrak: Efektivitas Gel Ekstrak Bawang Putih terhadap Proses Penyembuhan Luka Fase Inflamasi. Fase inflamasi merupakan respon tubuh yang menguntungkan sebagai mekanisme perlindungan. Pada proses penyembuhan luka menjadi fase yang sangat penting. Penatalaksanaan inflamasi yang sering digunakan Anti-Inflamasi Non Steroid golongan salisilat pada kulit yang memiliki efek samping. Kandungan zat allicin pada bawang putih dapat dimanfaatkan untuk masalah yang diawali dengan fase inflamasi. Pemanfaatan gel dari ekstrak bawang putih pun dalam penggunaannya lebih mudah diabsorsi dan mudah dibersihkan. Penelitian ini bertujuan untuk mengetahui efektifitas gel ekstrak bawang putih terhadap proses penyembuhan luka fase inflamasi. Penelitian ini merupakan penelitian eksperiment dengan metode pre and post test with control grup dengan jumlah sampel sebanyak 24 ekor tikus. Dilakukan perlukaan pada daerah punggung tikus panjang luka 1 cm, kedalaman sampai dermis. Dilakukan perawatan luka, diberi gel ekstrak bawang putih konsentrasi berbeda yaitu 20%, 40%, 80% kontrol menggunakan kompres NaCl 0,9%. Hasil uji Kruskal Wallis dan Anova oneway menunjukkan konsentrasi 20%, 40%, dan 80% nilai sig <0,05 yaitu 0,00. Disimpulkan bahwa 20%, 40%, 80% gel ekstrak bawang putih efektif terhadap proses penyembuhan luka inflamasi. Penggunaan gel ekstrak bawang putih lebih efektif dalam proses penyembuhan luka inflamasi luka. Disimpulkan bahwa 20%, 40%, 80% gel ekstrak bawang putih efektif terhadap proses penyembuhan luka inflamasi. Penggunaan gel ekstrak bawang putih lebih efektif dalam proses penyembuhan luka inflamasi luka.

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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

American Journal Of Pathology ◽

10.1016/j.ajpath.2020.05.010 ◽

2020 ◽

Vol 190 (9) ◽

pp. 1789-1800 ◽

Cited By ~ 1

Author(s):

Pablo Cassaglia ◽

Federico Penas ◽

Celeste Betazza ◽

Florencia Fontana Estevez ◽

Verónica Miksztowicz ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Remodeling ◽

Temporal Evolution ◽

Macrophage Infiltration ◽

Galectin 3 ◽

Genetic Deletion ◽

And Function

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Overcoming the Inflammatory Stage of Non-Healing Wounds: In Vitro Mechanism of Action of Negatively Charged Microspheres (NCMs)

Nanomaterials ◽

10.3390/nano10061108 ◽

2020 ◽

Vol 10 (6) ◽

pp. 1108

Author(s):

Edorta Santos-Vizcaino ◽

Aiala Salvador ◽

Claudia Vairo ◽

Manoli Igartua ◽

Rosa Maria Hernandez ◽

...

Keyword(s):

Wound Healing ◽

Mechanism Of Action ◽

Healing Process ◽

Dermal Fibroblasts ◽

Control Group ◽

Promote Cell Proliferation ◽

Inflammatory Phase ◽

Inflammatory State ◽

Diabetic Wounds

Negatively charged microspheres (NCMs) represent a new therapeutic approach for wound healing since recent clinical trials have shown NCM efficacy in the recovery of hard-to-heal wounds that tend to stay in the inflammatory phase, unlocking the healing process. The aim of this study was to elucidate the NCM mechanism of action. NCMs were extracted from a commercial microsphere formulation (PolyHeal® Micro) and cytotoxicity, attachment, proliferation and viability assays were performed in keratinocytes and dermal fibroblasts, while macrophages were used for the phagocytosis and polarization assays. We demonstrated that cells tend to attach to the microsphere surface, and that NCMs are biocompatible and promote cell proliferation at specific concentrations (50 and 10 NCM/cell) by a minimum of 3 fold compared to the control group. Furthermore, NCM internalization by macrophages seemed to drive these cells to a noninflammatory condition, as demonstrated by the over-expression of CD206 and the under-expression of CD64, M2 and M1 markers, respectively. NCMs are an effective approach for reverting the chronic inflammatory state of stagnant wounds (such as diabetic wounds) and thus for improving wound healing.

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Effects of montelukast on burn wound healing in a rat model

Clinical & Investigative Medicine ◽

10.25011/cim.v33i6.14593 ◽

2010 ◽

Vol 33 (6) ◽

pp. 413 ◽

Cited By ~ 11

Author(s):

Muhammet G Turtay ◽

Cemal Firat ◽

Emine Samdanci ◽

Hakan Oguzturk ◽

Serkan Erbatur ◽

...

Keyword(s):

Wound Healing ◽

Rat Model ◽

Macrophage Infiltration ◽

Control Group ◽

Fibroblast Proliferation ◽

Burn Wound ◽

Leukotriene D4 ◽

Topical Antibiotics ◽

Burn Wound Healing ◽

Local Burn

Purpose: Montelukast, a selective cysteinyl leukotriene D4-receptor antagonist, is used in the treatment of asthma. In a rat model, our aim was to investigate the effects of montelukast, alone or in combination with topical antibiotics, on local burn wound healing. Methods: Rats were randomly allocated to four groups after local burn development: Group 1; rats were left to secondary healing without treatment, Group 2; a dose of 10 mg/kg montelukast was given by gastric gavage once a day for 10 days, Group 3; rats were treated with topical pomade (bacitracin neomycin sulphate), and Group 4; rats were treat with a combination of topical antibiotic and montelukast (10 mg/kg were given by gastric gavage once a day for 10 days). Skin biopsies were taken on days 3, 10, 14, and 20 relative to burn induction. Results: Reepithelialization in the pomade and montelukast+pomade groups on the 10th day was significantly greater, in comparison with control and montelukast groups (p < 0.05). For the montelukast group, edema (on the 14th day) and angiogenesis, fibroblast proliferation, edema and macrophage infiltration (on the 20th day) were statistically improved in comparison with the control group (p < 0.05). For the montelukast+pomade group, angiogenesis, fibroblast proliferation and macrophage infiltration (on the 10th day), and angiogenesis, fibroblast proliferation, edema and macrophage infiltration (on the 14th and 20th days) were statistically improved in comparison with the control group (p < 0.05). Conclusion: In conclusion, montelukast was effective on burn wound healing. Moreover, the effect was amplified when combined with topical antibiotics applied in the early stage of burn wound healing.

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HE EFFECT OF BINJAI LEAVES EXTRACT (Mangifera caesia) ON INCISIONAL BACK WOUND OF MICE (Mus musculus) TO THE NUMBER OF NEUTROPHIL CELLS (Preliminary Study of Drug Preparations for Wound Healing)

Dentino : Jurnal Kedokteran Gigi ◽

10.20527/dentino.v5i1.8116 ◽

2020 ◽

Vol 5 (1) ◽

pp. 21

Author(s):

Desty Ayu Dwiyanti ◽

Irham Taufiqurrahman ◽

Didit Aspriyanto

Keyword(s):

Wound Healing ◽

Healing Process ◽

Negative Control Group ◽

Negative Control ◽

Control Group ◽

Wound Healing Process ◽

Control Group Design ◽

Group Design ◽

Inflammatory Phase ◽

Significant Difference

Background: Ethanol extract of binjai leaves contain bioactive compounds in the form of flavonoid and saponin which is potential as anti-inflammatory, so it will be able to control the wound healing process. Binjai leaves extract can affect the number of neutrophil on inflammatory phase, as it is characterized by neutrophil cells infiltration to the wound tissue, so its number will increase at the beginning of inflammatory phase and decrease on the 3rd day. Objective: To prove the effect of binjai leaves extract in 1 mg/mL, 2 mg/mL, and 3 mg/mL which given topically to the number of neutrophil in day 1, 3, and 5 of wound incision on the back of male mice. Methods: The study design was a pure laboratory experimental study with post-test only with control group design which involved 36 mice divided into 4 groups: negative control group design which was given BR2 feed, treatment group which was given binjai leaves extract in 1 mg/mL, 2 mg/mL, and 3 mg/mL. Results: The result of One-way ANOVA showed that there was significant difference of all groups in day 1 (p=0.000), day 3 (p=0.001), and day 5 (p=0.000). Post-Hoc LSD test showed that there was significant difference (p<0.05) between the negative control group and treatment groups. Conclusion: Binjai leaves extract has an effect to increase the number of neutrophil in day 1 and decrease the number of neutrophil in day 3 and 5 on the healing of back wound incision in mice.

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