Dataset Information

Inhibiting the mobilization of Ly6C(high) monocytes after acute myocardial infarction enhances the efficiency of mesenchymal stromal cell transplantation and curbs myocardial remodeling.

ABSTRACT: BACKGROUND:Ischemia related inflammation is the most critical factor for the survival of transplanted mesenchymal stem cells (MSCs), and strategies for controlling excessive inflammation after acute myocardial infarction (AMI) are essential and necessary for cell transplantation therapy. Our present study tested the effect of decreased Ly6C(high) monocytes on mouse MSCs transplantation after AMI. METHODS:BALB/c AMI mice were treated systemically with a CCR2 antagonist (RS 504393, 2 mg/kg, subcutaneously) or normal saline (control group). Next, 10(5) EdU-labeled MSCs were administered by intramyocardial injection to the mice in each group. TUNEL kits were used to identify the apoptotic cardiomyocytes in the infarct. The slides of the infarct border zone were stained with wheat germ agglutinin to measure the vessel density, and anti-myosin heavy chain eFluor 660 was used to measure the cardiac myosin-positive area. A transwell chamber was used to examine the interactions between Ly6C(high) monocytes and MSCs. The inflammatory cytokines expressed by Ly6C(high) monocytes and the SDF-1 expressed by MSCs were detected using ELISA kits. MSC viability was further examined by MTT and mitochondrial membrane potential assays by flow cytometry using JC-1 kits. RESULTS:We first observed the increased survival of transplanted MSCs (11.2 ± 3.4/mm(2) vs. 3.5 ± 1.6/mm(2), p < 0.001), and the decreased apoptosis of cardiomyocytes (11.20% ± 3.55% vs. 20.51% ± 8.17%, p < 0.001) in the infarcts at 3 days in the CCR2 antagonist group. An increased number of capillaries and small arterioles (139.6 ± 21.7/mm(2) vs. 95.4 ± 17.6/mm(2), p < 0.001) and an increased cardiac myosin-positive area (17.9% ± 6.6% vs. 11.8% ± 3.5%, p < 0.001) were also observed in the infarct zone at 21 days post MSC infusion in the CCR2 antagonist group. In addition, a significantly increased LvEF% (50.17 ± 10.06 vs. 45.44 ± 9.45, p < 0.001) was detected at the same time compared to the control mice. We further demonstrated that both the mitochondrial membrane potential of the MSCs (0.45 ± 0.11 vs. 3.4 ± 0.3, p < 0.001) and stromal cell-derived factor-1 (SDF-1) secreted by the MSCs significantly decreased (80.77 ± 39.02 pg/ml vs. 435.5 ± 77.41 pg/ml, p < 0.001) when co-cultured with Ly6C(high) monocytes. This is possibly mediated by the over-expressed cytokines secreted by the Ly6C(high) monocytes compared to the Ly6C(low) monocytes, including IL-1 (139.45 ± 30.44 vs. 80.05 ± 19.33, p < 0.001), IL-6 (187.82 ± 40.43 vs. 135.5 ± 22.09, p < 0.001), TNF-? (121.77 ± 31.65 vs. 75.3 ± 22.14, p < 0.001) and IFN-? (142.46 ± 27.55 vs. 88.25 ± 19.91, p < 0.001).

SUBMITTER: Lu W

PROVIDER: S-EPMC4448197 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Inhibiting the mobilization of Ly6C(high) monocytes after acute myocardial infarction enhances the efficiency of mesenchymal stromal cell transplantation and curbs myocardial remodeling.

Lu Wenbin W Tang Yong Y Zhang Ziwei Z Zhang Xiaofeng X Yao Yuyu Y Fu Cong C Wang Xin X Ma Genshan G

American journal of translational research 20150315 3

<h4>Background</h4>Ischemia related inflammation is the most critical factor for the survival of transplanted mesenchymal stem cells (MSCs), and strategies for controlling excessive inflammation after acute myocardial infarction (AMI) are essential and necessary for cell transplantation therapy. Our present study tested the effect of decreased Ly6C(high) monocytes on mouse MSCs transplantation after AMI.<h4>Methods</h4>BALB/c AMI mice were treated systemically with a CCR2 antagonist (RS 504393, ...[more]

PMID: 26045897

Similar Datasets

Project description:Background Ventricular arrhythmia after myocardial infarction is the most important risk factor for sudden cardiac death, which poses a serious threat to human health. As the correlation between autonomic nervous systemic dysfunction and heart rhythm abnormality has been gradually revealed, remedies targeting autonomic nervous system dysfunction, especially the sympathetic nerve, have emerged. Among them, renal denervation is noted for its powerful effect on the inhibition of sympathetic nerve activity. We aim to investigate whether renal denervation can reduce ventricular arrhythmia after myocardial infarction and thus decrease the risk of sudden cardiac death. In addition, we explore the potential mechanism with respect to nerve activity and remodeling. Methods and Results Twenty-four beagles were randomized into the control (n=4), renal denervation (n=10), and sham (n=10) groups. Permanent left anterior descending artery ligation was performed to establish myocardial infarction in the latter 2 groups. Animals in the renal denervation group underwent both surgical and chemical renal denervation. Compared with dogs in the sham group, dogs in the renal denervation group demonstrated attenuated effective refractory period shortening and inhomogeneity, flattened restitution curve, increased ventricular threshold, and decreased ventricular arrhythmia. Heart rate variability assessment, catecholamine measurement, and nerve discharge recordings all indicated that renal denervation could reduce whole-body and local tissue sympathetic tone. Tissue analysis revealed a significant decrease in neural remodeling in both the heart and stellate ganglion. Conclusions Surgical and chemical renal denervation decreased whole-body and local tissue sympathetic activity and reversed neural remodeling in the heart and stellate ganglion. Consequently, renal denervation led to beneficial remodeling of the electrophysiological characteristics in the infarction border zone, translating to a decrease in ventricular arrhythmia after myocardial infarction.

Project description:Monocytes consist of two well-defined subsets, the Ly6C+ and Ly6C- monocytes. Both CD11b+ myeloid cells populations have been proposed to infiltrate tissues during inflammation. While infiltration of Ly6C+ monocytes is an established pathogenic factor during hepatic inflammation, the role of Ly6C- monocytes remains elusive. Mice suffering experimental African trypanosome infection die from systemic inflammatory response syndrome (SIRS) that is initiated by phagocytosis of parasites by liver myeloid cells and culminates in apoptosis/necrosis of liver myeloid and parenchymal cells that reduces host survival. C57BL/6 mice are considered as trypanotolerant to Trypanosoma congolense infection. We have reported that in these animals, IL-10, produced among others by myeloid cells, limits the liver damage caused by pathogenic TNF-producing Ly6C+ monocytes, ensuring prolonged survival. Here, the heterogeneity and dynamics of liver myeloid cells in T. congolense-infected C57/BL6 mice was further dissected. Moreover, the contribution of Ly6C- monocytes to trypanotolerance was investigated. By using FACS analysis and adoptive transfer experiments, we found that the accumulation of Ly6C- monocytes and macrophages in the liver of infected mice coincided with a drop in the pool of Ly6C+ monocytes. Pathogenic TNF mainly originated from Ly6C+ monocytes while Ly6C- monocytes and macrophages were major and equipotent sources of IL-10 within myeloid cells. Moreover, Nr4a1 (Nur77) transcription factor-dependent Ly6C- monocytes exhibited IL-10-dependent and cell contact-dependent regulatory properties contributing to trypanotolerance by suppressing the production of TNF by Ly6C+ monocytes and by promoting the differentiation of the latter cells into macrophages. Thus, Ly6C- monocytes can dampen liver damage caused by an extensive Ly6C+ monocyte-associated inflammatory immune response in T. congolense trypanotolerant animals. In a more general context, Ly6C- or Ly6C+ monocyte targeting may represent a therapeutic approach in liver pathogenicity induced by chronic infection.

Project description:BackgroundThis study aimed to investigate the hypothesis that specific pattern of myocardial work (MW) distribution in patients with acute anterior ST-segment elevation myocardial infarction (STEMI) could provide prognostic value for predicting left ventricular (LV) remodeling.MethodsA total of 98 first anterior wall STEMI patients treated with primary percutaneous coronary intervention [85 men (86.7%), mean age: 58 ± 12 years] were enrolled. Transthoracic echocardiography was performed 24-72 h after angioplasty and during 3-month follow-up. MW was estimated from the left ventricular pressure-strain loop derived from speckle tracking echocardiography and simultaneous noninvasive brachial artery cuff pressure. The primary endpoint was early LV remodeling, defined as an increase in LV end-diastolic volume ≥20% compared with baseline at 3 months after STEMI. Major adverse cardiac events and combined clinical outcomes were recorded.ResultsLV remodeling was present in 32 patients (33%), who exhibited lower global and culprit-regional work index (WI), constructive work (CW), work efficiency (WE), and specifically, greater differences of WE (delta-WE) and CW (delta-CW) between the culprit and non-culprit region than those without LV remodeling both at the acute phase and follow-up (all P < 0.0125). During follow-up, all global and regional WI, CW, and WE were improved (P < 0.0125 compared with baseline), with less improvement in patients with LV remodeling. In multivariate analysis, baseline delta-WE (odds ratio: 2.304; 95% CI: 1.093-4.856, P = 0.028) and peak troponin I level (odds ratio: 1.035; 95%CI: 1.008-1.063, P = 0.010) were independently associated with early LV remodeling. Patients with greater delta-WE at baseline were associated with a higher incidence of heart failure and combined clinical outcomes during follow-up.ConclusionAfter reperfused acute anterior STEMI, patients with LV remodeling presented with more inhomogeneous MW distribution. The absolute difference of WE between culprit and non-culprit territory at the acute phase is an independent predictor for early LV remodeling.Clinical trial registrationwww.ClinicalTrials.gov, identifier: NCT05107102.

Dataset Information

Inhibiting the mobilization of Ly6C(high) monocytes after acute myocardial infarction enhances the efficiency of mesenchymal stromal cell transplantation and curbs myocardial remodeling.

Publications

Inhibiting the mobilization of Ly6C(high) monocytes after acute myocardial infarction enhances the efficiency of mesenchymal stromal cell transplantation and curbs myocardial remodeling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets