scholarly journals Myoblast transplantation improves cardiac function after myocardial infarction through attenuating inflammatory responses

Oncotarget ◽  
2017 ◽  
Vol 8 (40) ◽  
pp. 68780-68794 ◽  
Author(s):  
Bo Wang ◽  
Likui Zhang ◽  
Hao Cao ◽  
Junqi Yang ◽  
Manya Wu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Inflammatory Responses ◽  
Myoblast Transplantation

Butyrate improves cardiac function and sympathetic neural remodeling following myocardial infarction in rats

2020 ◽  
Vol 98 (6) ◽  
pp. 391-399
Author(s):  
Xiaojie Jiang ◽  
Xin Huang ◽  
Yifan Tong ◽  
Hong Gao
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Nerve Fibers ◽  
Border Zone ◽  
M2 Macrophage ◽  
Butyrate Treatment ◽  
Infarct Border Zone ◽  
Neural Remodeling

Increased inflammation is found in cardiac sympathetic neural remodeling with malignant ventricular arrhythmia (VA) following myocardial infarction (MI). Butyrate, as a microbiota-derived short-chain fatty acid, can inhibit inflammation and myocardial hypertrophy. However, the role of butyrate in sympathetic neural remodeling after MI is unknown. This study aimed to investigate whether butyrate could improve cardiac dysfunction and VA following MI by regulating inflammation and sympathetic neural remodeling. MI rats were randomized to administrate the butyrate or vehicle through intraperitoneal injection to undergo the study. Our data demonstrated that butyrate treatment preserved the partial cardiac function at 7 days post-MI. Butyrate downregulated the expression of essential for inflammatory response in the infarct border zone at 3 days post-MI. Particularly, butyrate promoted expression of M2 macrophage markers. Increased expressions of nerve growth factor and norephinephrine at 7 days after MI were inhibited in butyrate-treated rats. Furthermore, butyrate significantly decreased the density of nerve fibers for growth-associated protein-43 and tyrosine hydroxylase and resulted in fewer episodes of inducible VA. In conclusion, butyrate administration ameliorated cardiac function and VA after MI possibly through promoting M2 macrophage polarization to suppress inflammatory responses and inhibit sympathetic neural remodeling and may present an effective pharmacological strategy for the prevention of MI-related remodeling.

scholarly journals Combinatorial treatment of acute myocardial infarction using stem cells and their derived exosomes resulted in improved heart performance

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Peisen Huang ◽  
Li Wang ◽  
Qing Li ◽  
Jun Xu ◽  
Junyan Xu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Stem Cell ◽  
Cardiac Function ◽  
Inflammatory Responses ◽  
Heart Function ◽  
Border Zone ◽  
Inflammatory Factor ◽  
Intramyocardial Injection

Abstract Background Bone marrow mesenchymal stem cells (MSCs) are among the most common cell types to be used and studied for cardiac regeneration. Low survival rate and difficult retention of delivered MSCs in infarcted heart remain as major challenges in the field. Co-delivery of stem cell-derived exosomes (Exo) is expected to improve the recruitment and survival of transplanted MSCs. Methods Exo was isolated from MSCs and delivered to an acute myocardial infarction (AMI) rat heart through intramyocardial injection with or without intravenous infusion of atrovastatin-pretreated MSCs on day 1, day 3, or day 7 after infarction. Echocardiography was performed to evaluate cardiac function. Histological analysis and ELISA test were performed to assess angiogenesis, SDF-1, and inflammatory factor expression in the infarct border zone. The anti-apoptosis effect of Exo on MSCs was evaluated using flow cytometry and Hoechst 33342 staining assay. Results We found that intramyocardial delivery of Exo followed by MSC transplantation (in brief, Exo+MSC treatment) into MI hearts further improved cardiac function, reduced infarct size, and increased neovascularization when compared to controls treated with Exo or MSCs alone. Of note, comparing the three co-transplanting groups, intramyocardially injecting Exo 30 min after AMI combined with MSCs transplantation at day 3 after AMI achieved the highest improvement in heart function. The observed enhanced heart function is likely due to an improved microenvironment via Exo injection, which is exemplified as reduced inflammatory responses and better MSC recruitment and retention. Furthermore, we demonstrated that pre-transplantation injection of Exo enhanced survival of MSCs and reduced their apoptosis both in vitro and in vivo. Conclusions Combinatorial delivery of exosomes and stem cells in a sequential manner effectively reduces scar size and restores heart function after AMI. This approach may represent as an alternative promising strategy for stem cell-based heart repair and therapy.

Abstract 14871: APD588, a Novel, Selective S1P Receptor Modulator, Regulates Inflammatory Responses and Attenuates Cardiac Dysfunction Following Experimental Myocardial Infarction in Mice

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nathalie Nguyen ◽  
Martina Zarak Crnkovic ◽  
Liomar A Neves ◽  
Hongjian Wang ◽  
Teresa Martinez ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
T Lymphocyte ◽  
Cardiac Remodeling ◽  
Cardiac Dysfunction ◽  
Lymphocyte Count ◽  
Inflammatory Responses ◽  
Receptor Modulator ◽  
S1p Receptor ◽  
Anti Inflammatory

Recent studies have determined that chronic inflammation contributes to left ventricular (LV) remodeling following myocardial infarction (MI) leading to heart failure (HF). Evidence points to a critical role of T lymphocytes in driving the maladaptive inflammatory process associated with adverse tissue remodeling and cardiac dysfunction. FTY720, a non-selective sphingosine 1-phosphate (S1P) receptor modulator, elicits anti-inflammatory effects via inhibition of lymphocyte egress from secondary lymphoid organs and has been reported to improve cardiac remodeling and function post-MI. We hypothesized that APD588, a next-generation S1P receptor modulator with optimized S1P 1,5 receptor selectivity, would prevent cardiac remodeling and dysfunction following MI through modulation of T lymphocyte-mediated inflammatory responses. Efficacy of APD588 on cardiac function was assessed using C57BL/6N mice (n=7-10 mice/group) with experimental MI induced by coronary artery occlusion. Vehicle (VEH) or APD588 (0.3 mg/kg) was administered orally once daily starting at Day 3 post-MI and continued until Day 28. Blood samples were collected at Days 7 and 28 for lymphocyte count. Echocardiographic measurements, including LV ejection fraction (LVEF), were performed on Days 7, 14, and 28 post-MI. Administration of APD588 following MI resulted in a reduction of lymphocyte count at Days 7 and 28 post-MI, but only reached significance in the latter (VEH: 3.3 ± 0.5 x10 3 /μL; APD588: 1.3 ± 0.2 x10 3 /μL). Decreased cardiac function was observed at Day 7 post-MI (LVEF: 27.7 ± 3.6%, MI vs 45.7 ± 0.6%, Sham). No difference in LVEF was observed 7 days post-MI, however APD588 significantly improved LVEF at Day 28 post-MI, compared to vehicle (APD588: 35.7 ± 3.9%; VEH: 25.3 ± 3.9%). Therapies targeting inflammation in the pathophysiology of HF have shown limited success in the clinic. Novel strategies based on advancements in understanding the underlying immunobiology are warranted. Our results demonstrate that APD588 was effective at regulating lymphocyte activity and improved cardiac functional recovery following MI in mice. This supports the potential of S1P receptor modulation and other T lymphocyte-directed strategies as a targeted anti-inflammatory approach in HF.

Abstract 16796: β2-Adrenergic Receptor Expression on Hematopoietic Cells is Critical for Survival Following Myocardial Infarction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Laurel A Grisanti ◽  
Ashley A Repas ◽  
Erhe Gao ◽  
Anna M Gumpert ◽  
Rhonda L Carter ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Bone Marrow ◽  
Cardiac Function ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Flow Cytometric Analysis ◽  
Receptor Expression ◽  
Cellular Migration ◽  
Chimeric Mice

β-adrenergic receptors (βAR) are critical regulators of cardiac function normally and during (HF). The importance of βAR on cardiomyocyte contractility and survival is well defined however, following myocardial infarction (MI), inflammatory responses occur, which are critical for healing and scar formation. Catecholamines acting through βAR, particularly the β2AR subtype, are known to modulate immune responses, however, the influence of β2AR in regulating the inflammatory response following MI is unknown. To investigate the contribution of β2AR on immune cells following myocardial infarction (MI), wild-type (WT) mice were irradiated and then received β2ARKO or WT control BM transplants to create immune cell specific knockout (KO) animals. Following bone marrow reconstitution, mice were subjected to MI and cardiac function and survival were monitored. Cardiac function, as assessed by echocardiography, did not differ between WT and β2ARKO chimeric mice. However, mice lacking β2ARKO in their BM resulted in 100% mortality from cardiac rupture within two weeks of receiving MI in contrast to their WT counterparts that had ~20% death. Masson trichrome staining demonstrated infarct expansion in β2ARKO chimeric mice occurred more rapidly than their WT counterparts. Flow cytometric analysis showed decreased mobilization of granulocytes from bone marrow in β2ARKO mice. Additionally, β2ARKO chimeric mice reductions in infiltrating monocyte/macrophage, neutrophil and mast cell populations in the heart with no change in total cell infiltration suggesting a disruption in the ratio of infiltrating immune cells. Alterations in chemokine receptor levels, particularly CCR2, on BM resulted in decreased cellular migration. These results demonstrate the critical role of β2AR in mounting an immune response and promoting healing following MI.

scholarly journals Activation of Aryl Hydrocarbon Receptor by ITE Improves Cardiac Function in Mice After Myocardial Infarction

2021 ◽  
Author(s):  
Eunhwa Seong ◽  
Jun‐Ho Lee ◽  
Sungmin Lim ◽  
Eun‐Hye Park ◽  
Eunmin Kim ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
T Cells ◽  
Regulatory T Cells ◽  
Cardiac Function ◽  
Aryl Hydrocarbon Receptor ◽  
Inflammatory Responses ◽  
Left Ventricular ◽  
M2 Macrophage ◽  
Aryl Hydrocarbon ◽  
Acute Mi

Background The immune and inflammatory responses play a considerable role in left ventricular remodeling after myocardial infarction (MI). Binding of AhR (aryl hydrocarbon receptor) to its ligands modulates immune and inflammatory responses; however, the effects of AhR in the context of MI are unknown. Therefore, we evaluated the potential association between AhR and MI by treating mice with a nontoxic endogenous AhR ligand, ITE (2‐[1’H‐indole‐3’‐carbonyl]‐thiazole‐4‐carboxylic acid methyl ester). We hypothesized that activation of AhR by ITE in MI mice would boost regulatory T‐cell differentiation, modulate macrophage activity, and facilitate infarct healing. Methods and Results Acute MI was induced in C57BL/6 mice by ligation of the left anterior descending coronary artery. Then, the mice were randomized to daily intraperitoneal injection of ITE (200 µg/mouse, n=19) or vehicle (n=16) to examine the therapeutic effects of ITE during the postinfarct healing process. Echocardiographic and histopathological analyses revealed that ITE‐treated mice exhibited significantly improved systolic function ( P <0.001) and reduced infarct size compared with control mice ( P <0.001). In addition, we found that ITE increased regulatory T cells in the mediastinal lymph node, spleen, and infarcted myocardium, and shifted the M1/M2 macrophage balance toward the M2 phenotype in vivo, which plays vital roles in the induction and resolution of inflammation after acute MI. In vitro, ITE expanded the Foxp3 + (forkhead box protein P3‐positive) regulatory T cells and tolerogenic dendritic cell populations. Conclusions Activation of AhR by a nontoxic endogenous ligand, ITE, improves cardiac function after MI. Post‐MI mice treated with ITE have a significantly lower risk of developing advanced left ventricular systolic dysfunction than nontreated mice. Thus, the results imply that ITE has a potential as a stimulator of cardiac repair after MI to prevent heart failure.

scholarly journals Author Correction: In vivo transduction of ETV2 improves cardiac function and induces vascular regeneration following myocardial infarction

2019 ◽  
Vol 51 (9) ◽  
pp. 1-1 ◽  
Author(s):  
Sunghun Lee ◽  
Dong Hun Lee ◽  
Bong-Woo Park ◽  
Ri Youn Kim ◽  
Anh Duc Hoang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Vascular Regeneration

Autologous skeletal myoblast transplantation attenuates left ventricular dilatation without improving cardiac function

2003 ◽  
Vol 9 (5) ◽  
pp. S1
Author(s):  
Patrick I. McConnell ◽  
Louis Astra ◽  
E.William Schneeberger ◽  
Doug Jacoby ◽  
Jonathan Dinsmore ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Left Ventricular ◽  
Ventricular Dilatation ◽  
Skeletal Myoblast ◽  
Left Ventricular Dilatation ◽  
Myoblast Transplantation
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