Targeting Wnt Signaling to Improve Wound Healing After Myocardial Infarction

2013 ◽  
pp. 355-380 ◽  
Author(s):  
Evangelos P. Daskalopoulos ◽  
Ben J. A. Janssen ◽  
W. Matthijs Blankesteijn
Keyword(s):  
Myocardial Infarction ◽  
Wound Healing ◽  
Wnt Signaling ◽  
Improve Wound Healing

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

2018 ◽  
Vol 33 (2) ◽  
pp. 70-76 ◽  
Author(s):  
A. E. Gombozhapova ◽  
Yu. V. Rogovskaya ◽  
M. S. Rebenkova ◽  
J. G. Kzhyshkowska ◽  
V. V. Ryabov
Keyword(s):  
Myocardial Infarction ◽  
Wound Healing ◽  
Cardiac Remodeling ◽  
Phenotypic Heterogeneity ◽  
Macrophage Infiltration ◽  
Myocardial Regeneration ◽  
Control Group ◽  
M2 Macrophage ◽  
Inflammatory Phase ◽  
Regenerative Phase

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.

Modulating senescent cells to improve wound healing with age

Cytotherapy ◽  
2021 ◽  
Vol 23 (5) ◽  
pp. S147
Author(s):  
U. Niyogi ◽  
M.J. Ouellette ◽  
M.A. Carlson
Keyword(s):  
Wound Healing ◽  
Improve Wound Healing

Foslip®-based photodynamic therapy as a means to improve wound healing

2011 ◽  
Vol 8 (4) ◽  
pp. 321-327 ◽  
Author(s):  
Julie Garrier ◽  
Lina Bezdetnaya ◽  
Catherine Barlier ◽  
Susanna Gräfe ◽  
François Guillemin ◽  
...  
Keyword(s):  
Wound Healing ◽  
Photodynamic Therapy ◽  
Improve Wound Healing

Abstract 17166: Myeloid-specific Deletion of the Glucocorticoid Receptor Increases Mitochondrial Oxidative Stress and Impairs Wound Healing After Myocardial Infarction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jonas Neuser ◽  
Daniela Fraccarollo ◽  
Jan P Tuckermann ◽  
Paolo Galuppo ◽  
Johann Bauersachs
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Wound Healing ◽  
Glucocorticoid Receptor ◽  
Mononuclear Cells ◽  
Flow Cytometric Analysis ◽  
Myeloid Cells ◽  
Coronary Artery Ligation ◽  
Mitochondrial Oxidative Stress ◽  
Specific Deletion

Background: Glucocorticoid administration impairs ischemic wound healing by inhibiting inflammation and angiogenesis via a glucocorticoid receptor (GR)-mediated transcriptional response. However, there are also apparently contradictory reports claiming protective effects of glucorticoid administration after myocardial infarction (MI). We investigated the role of the GR in myeloid cells for infarct wound healing, using GR deficient mice (GRLysMCre). Methods and Results: MI was induced by permanent left coronary artery ligation in GRflox (wild-type [WT] controls) and GRLysMCre mice. The 7-day mortality was significantly lower in WT compared with GRLysMCre mice. At 7 days post MI, GRLysMCre mice exhibited significantly enhanced thinning and dilatation of the infarcted wall, LV chamber enlargement and functional deterioration. This was associated with altered granulation tissue formation and impaired neoangiogenesis at the site of ischemic injury. Multicolor flow cytometric analysis and immunohistochemical studies revealed at the 2nd day post infarction less infiltrating mononuclear cells [CD11bhigh and (CD49b, NK1.1, B220, CD90, Ly6G)low] in the healing myocardium of GRLysMCre mice. Mononuclear cells were identified as monocytes (F4/80, I-Ab, CD11c)low and as macrophages/dendritic cells (F4/80, I-Ab, CD11c)high. Monocytes lacking GR, isolated from peripheral blood and spleen by magnetic-activated cell sorting 1 day after MI, displayed reduced migration capacity and increased superoxide anion production in mitochondria, which was detected by HPLC-electrochemical analysis of Mito-2-hydroxy-E+. Moreover, at day 2 and 3 we found enhanced cellular and mitochondrial oxidative stress in the healing myocardium of GRLysMCre mice. Conclusions: Myeloid-specific deletion of the GR increasing mitochondrial oxidative stress alters wound healing and promotes infarct expansion. Our results suggest that the GR in myeloid cells play a crucial role during cardiac repair after myocardial infarction.

scholarly journals Quantitative and qualitative composition of the innate immune response are equally important in wound healing after myocardial infarction

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
J Wrobel ◽  
J Rettkowski ◽  
H Seung ◽  
C Wadle ◽  
P Stachon ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cell Cycle ◽  
Wound Healing ◽  
Innate Immunity ◽  
Cardiac Function ◽  
Ventricular Remodeling ◽  
Myeloid Cells ◽  
Fold Increase ◽  
Remote Myocardium ◽  
Inflammatory Phenotype

Abstract Background Emergency hematopoiesis (EH) serves as the foundation of monocyte-derived and macrophage (Mφ) driven efferocytosis and ventricular remodeling after myocardial infarction (MI). Excessive myelopoiesis, however, can stipulate maladaptive wound healing and its therapeutic reduction may be a novel approach to preserve cardiac function. All-trans retinoic acid (ATRA) is a pleiotropic modulator of EH and innate immunity shielding hematopoietic stem cells from activation and driving survival and differentiation of myeloid cells. Purpose This study aimed to investigate this intriguing interplay of ATRA in wound healing after MI. Methods MI was induced by permanent coronary ligation in C57BL/6 mice and treated with daily injections of either ATRA (30mg/kg) or DMSO (vehicle) up to five days, starting 24h after ligation. Flow cytometry (FACS) was used for cell cycle analysis and immunophenotyping of leukocytes in bone marrow (BM), blood and heart. Immunohistochemistry (IH), masson trichrome (MT) staining and echocardiography evaluated inflammatory-fibrotic and functional development. Cytokine expression was analyzed by qPCR in bulk infarct and isolated, polarized Mφ-populations of BM-derived and cardiac resident origin. Results On day 2 after MI, EH was significantly reduced in ATRA-treated mice as compared to vehicle controls by means of cell cycle activity (n=6–13 per group; p<0,01) and myeloid cells in BM, blood and infarct tissue (n=5–13; p<0,05). Consequently, mRNA-expression of key inflammatory cytokines, IL-1β and TNFα, was diminished in the infarct tissue in this early phase (n=5–12; p<0,05). These changes, however, failed to preserve cardiac function and ventricular remodeling, 21 days after MI (n=10–11; not significant). By qPCR, non-canonical activation of recruited ATRA-primed monocyte-derived Mφ, was found to propagate a pro-inflammatory phenotype with higher expression of MMP2 and MMP9 in sorted cardiac Mφ (n=4–5; p<0,001). Furthermore, prominent IL-1β-expression in M2-polarized BM-derived Mφ indicated an impaired anti-inflammatory phenotype after ATRA treatment (n=4–6; p<0,05). Strikingly, these changes also occurred in remote myocardium where IH revealed a 2-fold increase of CD11b - positive myeloid cells accompanied by increased expression of TNFα and TGFβ (n=9; p<0,001). MT-staining, performed 21 days after MI, demonstrated an almost 3-fold increase in collagen deposition in remote myocardium of ATRA treated mice in contrast to vehicle controls (n=4–6; p<0,0001). Conclusion Despite a beneficial reduction of EH after MI, short-term treatment with ATRA induced profound and persisting changes in the cytokine expression of monocyte-derived Mφ, which significantly altered their function and thus prevented improvements in cardiac function. Our data provide evidence that quantitative and qualitative changes in innate immunity are equally important for cardiac remodeling after MI. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft

scholarly journals Surgical Suture Assembled with Tadalafil/Polycaprolactone Drug-Delivery for Vascular Stimulation Around Wound: Validated in a Preclinical Model

2020 ◽  
Vol 10 (5) ◽  
pp. 6317-6327 ◽  
Keyword(s):  
Wound Healing ◽  
Tensile Strength ◽  
Drug Release ◽  
Study Groups ◽  
Preclinical Model ◽  
Surgical Suture ◽  
Electrospinning Method ◽  
Hematoxylin And Eosin ◽  
Improve Wound Healing

In this study, a novel Polycaprolactone suture assembled with Tadalafil was investigated to improve wound healing processes via vascular stimulation. Tadalafil/Polycaprolactone (TP) suture was developed by the electrospinning method. The designed suture was characterized by SEM, mechanical properties assessments, tensile strength measurements and the drug release study. For in vivo tests, rats were classified into two study groups. An incision was made on their back skin and they were sutured with TP suture and Polycaprolactone suture as control. Rats were sacrificed at 7 days following surgery for histopathological examinations with Hematoxylin and Eosin staining. Results of Tensile test demonstrated that the lowest tensile strength belonged to 3 and 4 % wt and the highest tensile strength belonged to 1 and 2 % wt of TP suture. The rate of Tadalafil release showed that the highest drug release was related to 3 and 4% wt which were about 125 to 210 μg during 15 days. The histopathology revealed that the number of blood vessels, collagen fibers, fibroblast, polymorphonuclear leukocytes, and epithelization was remarkable in Tadalafil/Polycaprolactone group during 7-day. A novel Tadalafil/Polycaprolactone suture improved the processes of wound healing by releasing the Tadalafil drug around the sutured wound and can be used in medical applications.

scholarly journals Matrix regeneration agents improve wound healing in non-stressed human corneal epithelial cells

Eye ◽  
2017 ◽  
Vol 32 (4) ◽  
pp. 813-819 ◽  
Author(s):  
A Robciuc ◽  
R P J Arvola ◽  
M Jauhiainen ◽  
J M Holopainen
Keyword(s):  
Wound Healing ◽  
Epithelial Cells ◽  
Corneal Epithelial Cells ◽  
Corneal Epithelial ◽  
Human Corneal Epithelial Cells ◽  
Improve Wound Healing

Dynamics of cardiac wound healing following myocardial infarction: observations in genetically altered mice

2001 ◽  
Vol 173 (1) ◽  
pp. 75-82 ◽  
Author(s):  
W. M. Blankesteijn ◽  
E. Creemers ◽  
E. Lutgens ◽  
J. P. M. Cleutjens ◽  
M. J. A. P. Daemen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Wound Healing ◽  
Cardiac Wound Healing
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