Dataset Information

Concomitant overexpression of triple antioxidant enzymes selectively increases circulating endothelial progenitor cells in mice with limb ischaemia.

ABSTRACT: Endothelial progenitor cells (EPCs) are a group of heterogeneous cells in bone marrow (BM) and blood. Ischaemia increases reactive oxygen species (ROS) production that regulates EPC number and function. The present study was conducted to determine if ischaemia-induced ROS differentially regulated individual EPC subpopulations using a mouse model concomitantly overexpressing superoxide dismutase (SOD)1, SOD3 and glutathione peroxidase. Limb ischaemia was induced by femoral artery ligation in male transgenic mice with their wild-type littermate as control. BM and blood cells were collected for EPCs analysis and mononuclear cell intracellular ROS production, apoptosis and proliferation at baseline, day 3 and day 21 after ischaemia. Cells positive for c-Kit⁺ /CD31⁺ or Sca-1⁺ /Flk-1⁺ or CD34⁺ /CD133⁺ or CD34⁺ /Flk-1⁺ were identified as EPCs. ischaemia significantly increased ROS production and cell apoptosis and decreased proliferation of circulating and BM mononuclear cells and increased BM and circulating EPCs levels. Overexpression of triple antioxidant enzymes effectively prevented ischaemia-induced ROS production with significantly decreased cell apoptosis and preserved proliferation and significantly increased circulating EPCs level without significant changes in BM EPC populations, associated with enhanced recovery of blood flow and function of the ischemic limb. These data suggested that ischaemia-induced ROS was differentially involved in the regulation of circulating EPC population.

SUBMITTER: Liu L

PROVIDER: S-EPMC6533526 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Concomitant overexpression of triple antioxidant enzymes selectively increases circulating endothelial progenitor cells in mice with limb ischaemia.

Liu Lingjuan L Cui Yuqi Y Li Xin X Que Xingyi X Xiao Yuan Y Yang Chunlin C Zhang Jia J Xie Xiaoyun X Cowan Peter J PJ Tian Jie J Hao Hong H Liu Zhenguo Z

Journal of cellular and molecular medicine 20190411 6

Endothelial progenitor cells (EPCs) are a group of heterogeneous cells in bone marrow (BM) and blood. Ischaemia increases reactive oxygen species (ROS) production that regulates EPC number and function. The present study was conducted to determine if ischaemia-induced ROS differentially regulated individual EPC subpopulations using a mouse model concomitantly overexpressing superoxide dismutase (SOD)1, SOD3 and glutathione peroxidase. Limb ischaemia was induced by femoral artery ligation in male ...[more]

PMID: 30973215

Similar Datasets

Project description:BACKGROUND:Peripheral arterial disease is a major health problem, and in about 1% to 2% of patients the disease progresses to critical limb ischaemia (CLI). In a substantial number of patients with CLI, no effective treatment option other than amputation is available and around a quarter of these patients will require a major amputation during the following year. This is an update of the review first published in 2011. OBJECTIVES:To determine the effectiveness and safety of local intramuscular transplantation of autologous adult bone marrow mononuclear cells (BMMNCs) as a treatment for critical limb ischaemia (CLI). SEARCH METHODS:For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched February 2014) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 1). SELECTION CRITERIA:We included all randomised controlled trials of CLI in which participants were randomly allocated to intramuscular administration of autologous adult BMMNCs or control (either no intervention or conventional conservative therapy). We excluded studies on patients with intermittent claudication. DATA COLLECTION AND ANALYSIS:Two authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. Disagreements were resolved by consensus or by the third author. MAIN RESULTS:Only two small studies, with a combined total of 57 participants, met our inclusion criteria and were finally included. They were classified as having a moderate risk of bias with unclear issues regarding their methods, and according to the GRADE approach, the overall quality of the evidence would be considered as moderate. In one study the effects of intramuscular injections of BMMNCs in the ischaemic lower limbs of patients with CLI were compared with control (standard conservative treatment). No deaths were reported and no significant difference was observed between the two groups for either pain (P = 0.37) or the ankle brachial index (ABI) parameter. However, the treatment group showed a significantly smaller proportion of participants undergoing amputation compared with the control group (P = 0.026).In the other study, following subcutaneous injections of granulocyte colony-stimulating factor (G-CSF) for five days, peripheral blood derived mononuclear cells were collected and then transplanted by intramuscular injections into ischaemic lower limbs. The effects were compared with daily intravenous prostaglandin E1 injections (control group). No deaths were reported. Pain reduction was greater in the treatment group than in the control group (P < 0.001) as was increase in ABI (mean increase 0.13 versus 0.02, P < 0.01). The treatment group experienced a statistically significant increase in pain-free walking distance (PFWD) compared with the control group (mean increase 306.4 m versus 78.6 m, P = 0.007). A smaller proportion of participants underwent amputation in the treatment group compared with the control group (0% versus 36%, P = 0.007). AUTHORS' CONCLUSIONS:The data from the published trials suggest that there is insufficient evidence to support this treatment. These results were based on only two trials which had a very small number of participants. Therefore evidence from larger randomised controlled trials is needed in order to provide adequate statistical power to assess the role of intramuscular mononuclear cell implantation in patients with CLI.

Project description:ObjectivePrevious studies have demonstrated amputation and mortality rates to be 14.3% - 30% and 11.4% - 28.9%, respectively, for all patients presenting with acute limb ischaemia (ALI). Rates of ALI are higher in patients with malignancy than in those without. Despite this, there remains uncertainty with regards to the most appropriate management for patients with cancer presenting with ALI. This is because of previously published high rates of associated morbidity and mortality in this population. The aim of this review was to summarise the available evidence reporting on outcomes of ALI in patients with underlying malignancy.MethodA systematic review was performed in August 2020 in accordance with the PRISMA guidelines. The Medline, Scopus, Cochrane, and Embase databases were searched with the following search string ((acute limb ischaemia) OR (acute limb ischemia)) AND ((cancer) OR (malignancy)). A total of 849 papers were identified and reviewed; six studies were included. Studies were assessed for bias using the National Institute of Health/National Heart, Lung and Blood Institute Quality Assessment Tool. Data including demographics, Rutherford classification, baseline performance scores, method of revascularisation, and peri-procedural outcomes were extracted and analysed. Data were pooled based on outcomes of interest and pooled prevalence was reported with 95% confidence intervals (CI).ResultsSix studies with 284 patients with cancer were included for analysis. The pooled overall risk of amputation was 15% (95% CI 5.9 - 26.9). The pooled 30 day mortality rate was 24% (95% CI 14.7 - 34.6).ConclusionDespite limitations of interstudy selection bias and some clinical heterogeneity, the included studies demonstrated acceptable short and medium term outcomes for patients with cancer undergoing revascularisation for acute limb ischaemia. This is in line with current recommendations that patients with underlying malignancy should be considered strongly for revascularisation.

Dataset Information

Concomitant overexpression of triple antioxidant enzymes selectively increases circulating endothelial progenitor cells in mice with limb ischaemia.

Publications

Concomitant overexpression of triple antioxidant enzymes selectively increases circulating endothelial progenitor cells in mice with limb ischaemia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets