Abstract 16841: Coaxial Anti-Inflammatory Scaffold Preserves the Phenotype of MSCs Under Stress

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Naveen Nagiah ◽  
Federico Franchi ◽  
Michaela Olthoff ◽  
Karen Peterson ◽  
Martin Rodriguez-Porcel
Keyword(s):  
Cardiac Remodeling ◽  
Animal Studies ◽  
Ischemia Reperfusion ◽  
Average Diameter ◽  
Rt Pcr ◽  
M1 Macrophages ◽  
Regional Cardiac Function ◽  
Anti Inflammatory ◽  
Myocardial Ischemia Reperfusion ◽  
Inflammatory Milieu

Introduction: Myocardial infarction is an inflammatory condition that leads to scar deposition and cardiac remodeling. Stem cells (SC) are an alternative to prevent cardiac remodeling, but have poor survival after transplanted to an pro-inflammatory ischemic myocardium. Polymeric biocompatible scaffolds are biomaterials that can improve SC retention and survival, with the goal to improve regional cardiac function. Methods: We electrospun fibers of a) uniaxial polycaprolactone (PCL) and b) coaxial PCL (core) and gelatin methacrylate (sheath), an anti-inflammatory substance. We first tested the SC retention of each scaffold. Then, adipose derived mesenchymal SCs (MSCs) were co-cultured with M1 macrophages (pro-inflammatory) with and without scaffold and we measure the expression of inflammatory-related genes (RT-PCR). Lastly, PCL+GelMA scaffolds with and without MSCs (3.5x10 3 MSCs) were implanted after myocardial ischemia/reperfusion (IR) and followed for 2 weeks. Results: The average diameter of PCL and PCL+GelMA fibers were 730±40nm and 1110±50nm, respectively. PCL+GelMA scaffolds increased MSCs adhesion compared to PCL (absorbance: 0.09±.03 for PCL and 0.24±0.02 for coaxial, p<0.05). Figure A shows that MSCs in presence of M1 macrophages had a significant increase in inflammatory genes, which was significantly ameliorated in the presence of GelMA. In preliminary animal studies (n=1-4), MSCs delivered in a PCL+GelMA scaffold had partial preservation of regional function parameteres compared to IR only or IR+PCL+GelMA (no MSCs) (Figure B). Conclusion: Coaxially PCL+gelMA scaffolds attenuate the pro-inflammatory milieu of MSCs under ischemic-like conditions, and may improve regional cardiac remodeling.

Abstract 17056: Nanoparticles-mediated Targeting of Pioglitazone Reduces Myocardial Ischemia-reperfusion Injury and Cardiac Remodeling by Antagonizing Monocyte-mediated Inflammation in Preclinical Animal Models

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Masaki Tokutome ◽  
Tetsuya Matoba ◽  
Yasuhiro Nakano ◽  
Kaku Nakano ◽  
Kensuke Egashira
Keyword(s):  
Animal Models ◽  
Myocardial Ischemia ◽  
Cardiac Remodeling ◽  
Ischemia Reperfusion ◽  
Therapeutic Effects ◽  
Inflammatory Monocytes ◽  
Intravenous Treatment ◽  
Anti Inflammatory ◽  
Myocardial Ischemia Reperfusion ◽  
Preclinical Animal Models

Background: Monocyte-mediated inflammation is a major mechanism of myocardial ischemia-reperfusion (IR) injury and cardiac remodeling. However, no anti-inflammatory therapy has been developed for clinical myocardial IR injury. Pioglitazone, a peroxisome proliferator-activated receptor (PPAR)γ agonist, has unique anti-inflammatory effects on monocyte/macrophage. Here we tested the hypothesis that nanoparticle-mediated targeting of pioglitazone into cardiomyocytes and inflammatory monocytes ameliorates IR injury and cardiac remodeling in preclinical animal models. Methods and Results: We formulated poly (lactic acid/glycolic acid) nanoparticle containing pioglitazone (Pio-NPs). In mouse IR model, nanoparticles were delivered predominantly to circulating monocytes and to cardiomyocytes and macrophages in the IR heart. Intravenous treatment with Pio-NPs containing ≥0.1 mg/kg of pioglitazone at the time of reperfusion reduced IR injury, which was canceled by the pretreatment with PPARγ antagonist GW9662 (Fig. A). In contrast, pioglitazone solution at doses up to 3.0 mg/kg showed no therapeutic effects (Fig. A). Pio-NPs reduced inflammatory gene expression and inhibited the recruitment of Ly6Chigh inflammatory monocytes into IR heart (Fig. B). Pio-NPs showed no therapeutic effects in mice lacking CCR2. In a mouse model of myocardial infarction, intravenous treatment with Pio-NPs for 3 days after LAD ligation attenuated cardiac remodeling, improved cardiac function, and reduced recruitment of macrophage and polarization of macrophages toward M2 phenotype (Fig. C, D). Finally, in a mini-pig model of myocardial IR injury, Pio-NPs induced cardioprotection from IR injury, indicating the pre-clinical proof of concept. Conclusion: Nanoparticle-mediated targeting of pioglitazone into cardiomyocytes and monocytes can be developed as a novel modality that offers organ protection by antagonizing monocyte-mediated inflammation in acute MI.

Inhibition of RIP1-dependent necrosis prevents adverse cardiac remodeling after myocardial ischemia–reperfusion in vivo

2012 ◽  
Vol 107 (4) ◽  
Author(s):  
Martinus I. F. J. Oerlemans ◽  
Jia Liu ◽  
Fatih Arslan ◽  
Krista Ouden ◽  
Ben J. Middelaar ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Cardiac Remodeling ◽  
Ischemia Reperfusion ◽  
Myocardial Ischemia Reperfusion

scholarly journals Light Emitting Diode Therapy Protects against Myocardial Ischemia/Reperfusion Injury through Mitigating Neuroinflammation

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Songyun Wang ◽  
Qinyu Luo ◽  
Hui Chen ◽  
Jingyu Huang ◽  
Xuemeng Li ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Light Emitting Diode ◽  
Ischemia Reperfusion ◽  
Microglia Activation ◽  
Light Emitting ◽  
M2 Microglia ◽  
Led Therapy ◽  
Anti Inflammatory ◽  
Myocardial Ischemia Reperfusion

Background. Neuroinflammation plays a key role in myocardial ischemia-reperfusion (I/R) injury. Previous studies showed that light-emitting diode (LED) therapy might improve M2 microglia activation and brain-derived neurotrophic factor (BDNF) expression, thereby exerting anti-inflammatory effects. Therefore, we hypothesized that LED therapy might reduce myocardial I/R injury by neuroinflammation modulation. Objective. To explore the effect of LED therapy on myocardial I/R-induced injury and seek the underlying mechanism. Methods. Thirty rats were randomly divided into three groups: Control group (without LED treatment or myocardial I/R, n=6), I/R group (with myocardial I/R only, n=12), and LED+I/R group (with myocardial I/R and LED therapy, n=12). Electrocardiogram was recorded continuously during the procedure. In addition, brain tissue was extracted for BDNF, Iba1, and CD206 analyses, and heart tissue for myocardial injury (ischemic size and infarct size), IL-4 and IL-10 mRNA analysis. Results. In comparison with the I/R group, the ischemia size and the infarct size were significantly attenuated by LED therapy in the LED+I/R group. Meanwhile, the microglia activation induced by I/R injury was prominently attenuated by LED treatment either. And it is apparent that there was also an increase in the beneficial neuroinflammation markers (BDNF and CD206) in the paraventricular nucleus (PVN) in the LED+I/R group. Furthermore, the anti-inflammatory cytokines, IL-4 and IL-10, were greatly decreased by I/R while improved by LED treatment in myocardium. Conclusion. LED therapy might reduce neuroinflammation in PVN and decrease myocardium injury by elevating BDNF and M2 microglia.

The Influence of Obese Insulin-Resistance on the Outcome of the Ischemia/Reperfusion Insult to the Heart

2018 ◽  
Vol 25 (13) ◽  
pp. 1501-1509 ◽  
Author(s):  
Krekwit Shinlapawittayatorn ◽  
Siriporn C. Chattipakorn ◽  
Nipon Chattipakorn
Keyword(s):  
Myocardial Infarction ◽  
Insulin Resistance ◽  
Clinical Trials ◽  
Reperfusion Injury ◽  
Clinical Studies ◽  
Animal Studies ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Ischemia Reperfusion ◽  
Underlying Mechanisms

Background: Obese insulin-resistance is one of the most important risk factor for cardiovascular diseases including ischemic heart disease (IHD). Growing evidences suggest that the susceptibility to myocardial ischemia-reperfusion (I/R) injury is increased in an obese insulin-resistance condition. Based on the currently available evidence from human and animal studies, this review mainly focuses on the influence of obese insulinresistance on the outcome of the I/R insult to the heart. Moreover, we have discussed whether improving insulin sensitivity by pharmacological interventions could ameliorate reperfusion induced myocardial injury. Methods: The electronic database Pubmed was used as the source of selected peerreviewed research articles published in English. Both pre-clinical studies and clinical trials were obtained using obesity, insulin resistance, ischemia-reperfusion injury and myocardial infarction as keywords. Results: Twenty-seven pre-clinical studies were obtained using obesity, insulin resistance, and cardiac ischemia-reperfusion injury as keywords, and five clinical trials were obtained using obesity, insulin resistance, and myocardial infarction as keywords. The underlying mechanisms responsible for the exacerbation of I/R injury in obese insulinresistance were the main subject of our review. Conclusion: The findings of this review suggest that the susceptibility to I/R injury is increased in an obese insulin-resistance condition. However, the underlying mechanisms responsible for the exacerbation of I/R injury in obese insulin-resistance have not been fully elucidated, but increased basal oxidative stress, the impairment of anti-oxidant capacities, insulin signaling and pro-survival signaling and increased inflammation, likely play an important role.

scholarly journals Atorvastatin Protects Myocardium Against Ischemia-Reperfusion Injury Through Inhibiting miR-199a-5p

2016 ◽  
Vol 39 (3) ◽  
pp. 1021-1030 ◽  
Author(s):  
YaBei Zuo ◽  
YuZhao Wang ◽  
HaiJuan Hu ◽  
Wei Cui
Keyword(s):  
Western Blot ◽  
Protein Level ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mrna Level ◽  
Underlying Mechanism ◽  
Protective Effects ◽  
Rt Pcr ◽  
Myocardial Ischemia Reperfusion ◽  
Gsk 3Β

Objective: This study aimed to evaluate the protective effects of atorvastatin against myocardial ischemia/reperfusion (I/R) injury in cardiomyocytes and its possible underlying mechanism. Method: Direct cytotoxic effect of OGD/R on cardiomyocytes with and without atorvastatin pretreatment was evaluated. Effects of atorvastatin on expression of GSK-3β and miR-199a-5p were determined using RT-PCR and Western blot. In addition, GSK-3β expression with miR-199a-5p upregulation and downregulation was detected using RT-PCR, Western blot, and immunohistochemistry. Results: Pretreatment with atorvastatin significantly improved the recovery of cells viability from OGD/R (p<0.05). In addition, the atorvastatin pretreatment significantly increased GSK-3β expression both in mRNA level and protein level and decreased miR-199a-5p expression in mRNA level (p<0.05). Upregulation and downregulation of miR-199a-5p respectively decreased and increased GSK-3β expression both in mRNA level and protein level. Conclusion: These results suggested that atorvastatin provides the cardioprotective effects against I/R injury via increasing GSK-3β through inhibition of miR-199a-5p.

scholarly journals Exosome Treatment Enhances Anti-Inflammatory M2 Macrophages and Reduces Inflammation-Induced Pyroptosis in Doxorubicin-Induced Cardiomyopathy

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1224 ◽  
Author(s):  
Dinender K. Singla ◽  
Taylor A. Johnson ◽  
Zahra Tavakoli Dargani
Keyword(s):  
Cell Signaling ◽  
Cardiac Remodeling ◽  
Heart Function ◽  
Es Cells ◽  
Antineoplastic Agent ◽  
Embryonic Stem ◽  
Signaling Proteins ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Anti Inflammatory

Doxorubicin (Dox) is an effective antineoplastic agent used to treat cancers, but its use is limited as Dox induces adverse cardiotoxic effects. Dox-induced cardiotoxicity (DIC) can lead to heart failure and death. There is no study that investigates whether embryonic stem cell-derived exosomes (ES-Exos) in DIC can attenuate inflammation-induced pyroptosis, pro-inflammatory M1 macrophages, inflammatory cell signaling, and adverse cardiac remodeling. For this purpose, we transplanted ES-Exos and compared with ES-cells (ESCs) to examine pyroptosis, inflammation, cell signaling, adverse cardiac remodeling, and their influence on DIC induced cardiac dysfunction. Therefore, we used C57BL/6J mice ages 10 ± 2 weeks and divided them into four groups (n = 6–8/group): Control, Dox, Dox + ESCs, and Dox + ES-Exos. Our data shows that the Dox treatment significantly increased expression of inflammasome markers (TLR4 and NLRP3), pyroptotic markers (caspase-1, IL1-β, and IL-18), cell signaling proteins (MyD88, p-P38, and p-JNK), pro-inflammatory M1 macrophages, and TNF-α cytokine. This increased pyroptosis, inflammation, and cell signaling proteins were inhibited with ES-Exos or ESCs. Moreover, ES-Exos or ESCs increased M2 macrophages and anti-inflammatory cytokine, IL-10. Additionally, ES-Exos or ESCs treatment inhibited significantly cytoplasmic vacuolization, myofibril loss, hypertrophy, and improved heart function. In conclusion, for the first time we demonstrated that Dox-induced pyroptosis and cardiac remodeling are ameliorated by ES-Exos or ESCs.

scholarly journals Protective anti-inflammatory effect of ADAMTS13 on myocardial ischemia/reperfusion injury in mice

Blood ◽  
2012 ◽  
Vol 120 (26) ◽  
pp. 5217-5223 ◽  
Author(s):  
Simon F. De Meyer ◽  
Alexander S. Savchenko ◽  
Michael S. Haas ◽  
Daphne Schatzberg ◽  
Michael C. Carroll ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ischemic Myocardium ◽  
Wild Type ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Anti Inflammatory ◽  
Myocardial Ischemia Reperfusion ◽  
Inflammatory Effect

Abstract Coronary heart disease is a major cause of death in the western world. Although essential for successful recovery, reperfusion of ischemic myocardium is inevitably associated with reperfusion injury. To investigate a potential protective role of ADAMTS13, a protease cleaving von Willebrand factor multimers, during myocardial ischemia/reperfusion, we used a mouse model of acute myocardial infarction. We found that Adamts13−/− mice developed larger myocardial infarctions than wild-type control mice, whereas treatment of wild-type mice with recombinant human ADAMTS13 (rhADAMTS13) led to smaller infarctions. The protective effect of ADAMTS13 was further confirmed by a significant reduction of cardiac troponin-I release and less myocardial apoptosis in mice that received rhADAMTS13 compared with controls. Platelets adherent to the blood vessel wall were observed in few areas in the heart samples from mice treated with vehicle and were not detected in samples from mice treated with rhADAMTS13. However, we observed a 9-fold reduction in number of neutrophils infiltrating ischemic myocardium in mice that were treated with rhADAMTS13, suggesting a potent anti-inflammatory effect of ADAMTS13 during heart injury. Our data show that ADAMTS13 reduces myocardial ischemia/reperfusion injury in mice and indicate that rhADAMTS13 could be of therapeutic value to limit myocardial ischemia/reperfusion injury.

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