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Bone marrow MiR-181a/b-CXCR4 signaling axis impairs hematopoiesis, monocytosis, and angiogenesis in diabetic critical limb ischemia [BM_HFSC]

ABSTRACT: We report transcriptomic changes in bone marrow cells of systemic miR-181a2b2 KO mice in response after HFSC diet feeding and hindlimb ischemia

ORGANISM(S): Mus musculus

PROVIDER: GSE196561 | GEO | 2023/10/01

REPOSITORIES: GEO

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Bone marrow MiR-181a/b-CXCR4 signaling axis impairs hematopoiesis, monocytosis, and angiogenesis in diabetic critical limb ischemia [SM_CHOW_HFSC]

Project description:We report transcriptomic changes in skeletal muscle of systemic miR-181a2b2 KO mice in response to chow and HFSC diet feeding and hindlimb ischemia

2023-10-01 | GSE196565 | GEO

Bone marrow MiR-181a/b-CXCR4 signaling axis impairs hematopoiesis, monocytosis, and angiogenesis in diabetic critical limb ischemia [BM_CHOW]

Project description:We report transcriptomic changes in bone marrow cells of systemic miR-181a2b2 KO mice in response after chow diet feeding and hindlimb ischemia

2023-10-01 | GSE196562 | GEO

Bone marrow MiR-181a/b-CXCR4 signaling axis impairs hematopoiesis, monocytosis, and angiogenesis in diabetic critical limb ischemia

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-10-01 | GSE196566 | GEO

Bone marrow MiR-181a/b-CXCR4 signaling axis impairs hematopoiesis, monocytosis, and angiogenesis in diabetic critical limb ischemia

Project description:Bone marrow MiR-181a/b-CXCR4 signaling axis impairs hematopoiesis, monocytosis, and angiogenesis in diabetic critical limb ischemia

| PRJNA805507 | ENA

Bone marrow MiR-181a/b-CXCR4 signaling axis impairs hematopoiesis, monocytosis, and angiogenesis in diabetic critical limb ischemia [BM_CHOW]

Project description:Bone marrow MiR-181a/b-CXCR4 signaling axis impairs hematopoiesis, monocytosis, and angiogenesis in diabetic critical limb ischemia [BM_CHOW]

| PRJNA806350 | ENA

Bone marrow MiR-181a/b-CXCR4 signaling axis impairs hematopoiesis, monocytosis, and angiogenesis in diabetic critical limb ischemia [SM_CHOW_HFSC]

Project description:Bone marrow MiR-181a/b-CXCR4 signaling axis impairs hematopoiesis, monocytosis, and angiogenesis in diabetic critical limb ischemia [SM_CHOW_HFSC]

| PRJNA806349 | ENA

Bone marrow MiR-181a/b-CXCR4 signaling axis impairs hematopoiesis, monocytosis, and angiogenesis in diabetic critical limb ischemia [BM_HFSC]

Project description:Bone marrow MiR-181a/b-CXCR4 signaling axis impairs hematopoiesis, monocytosis, and angiogenesis in diabetic critical limb ischemia [BM_HFSC]

| PRJNA805508 | ENA

A miRNA/CXCR4 signaling axis impairs monopoiesis and angiogenesis in diabetic critical limb ischemia.

Project description:Patients with peripheral artery disease (PAD) and diabetes have the highest risk of critical limb ischemia (CLI) and amputation, yet the underlying mechanisms remain incompletely understood. MicroRNA (miRNA) sequencing of plasma from diabetic patients with or without CLI was compared to diabetic mice with acute or subacute limb ischemia to identify conserved miRNAs. miRNA-KO mice on high-fat diet were generated to explore the impact on CLI. Comparison of dysregulated miRNAs from diabetic individuals with PAD and diabetic mice with limb ischemia revealed conserved miR-181 family members. High-fat-fed, diabetic Mir181a2b2-KO mice had impaired revascularization in limbs due to abrogation of circulating Ly6Chi monocytes, with reduced accumulation in ischemic skeletal muscles. M2-like KO macrophages under diabetic conditions failed to produce proangiogenic cytokines. Single-cell transcriptomics of the bone marrow niche revealed that the reduced monocytosis in diabetic KO mice was a result of impaired hematopoiesis, with increased CXCR4 signaling in bone marrow Lineage-Sca1+Kit+ (LSK) cells. Exogenous Ly6Chi monocytes from nondiabetic KO mice rescued the impaired revascularization in ischemic limbs of diabetic KO mice. Increased Cxcr4 expression was mediated by the miR-181 target, Plac8. Taken together, our results show that MiR-181a/b is a putative mediator of diabetic CLI and contributes to changes in hematopoiesis, monocytosis, and macrophage polarization.

| S-EPMC10132154 | biostudies-literature

Myocyte specific overexpression of myoglobin impairs angiogenesis after hind-limb ischemia.

Project description:ObjectiveIn preclinical models of peripheral arterial disease the angiogenic response is typically robust, though it can be impaired in conditions such as hypercholesterolemia and diabetes where the endothelium is dysfunctional. Myoglobin (Mb) is expressed exclusively in striated muscle cells. We hypothesized that myocyte specific overexpression of myoglobin attenuates ischemia-induced angiogenesis even in the presence of normal endothelium.Methods and resultsMb overexpressing transgenic (MbTg, n=59) and wild-type (WT, n=56) C57Bl/6 mice underwent unilateral femoral artery ligation/excision. Perfusion recovery was monitored using Laser Doppler. Ischemia-induced changes in muscle were assessed by protein and immunohistochemistry assays. Nitrite/nitrate and protein-bound NO, and vasoreactivity was measured. Vasoreactivity was similar between MbTg and WT. In ischemic muscle, at d14 postligation, MbTg increased VEGF-A, and activated eNOS the same as WT mice but nitrate/nitrite were reduced whereas protein-bound NO was higher. MbTg had attenuated perfusion recovery at d21 (0.37+/-0.03 versus 0.47+/-0.02, P<0.05), d28 (0.40+/-0.03 versus 0.50+/-0.04, P<0.05), greater limb necrosis (65.2% versus 15%, P<0.001), a lower capillary density, and greater apoptosis versus WT.ConclusionsIncreased Mb expression in myocytes attenuates angiogenesis after hind-limb ischemia by binding NO and reducing its bioavailability. Myoglobin can modulate the angiogenic response to ischemia even in the setting of normal endothelium.

| S-EPMC3152376 | biostudies-literature

A novel model of chronic limb ischemia with translational significance enables proper evaluation of therapeutic angiogenesis

Project description:We aimed to develop a novel chronic and severe hindlimb ischemia mice model to properly evaluate the therapeutic effects of drug candidates in translational research for critical limb ischemia treatments. We used microarray to compare the gene expression patterns of gastrocnemius muscles at 1st week and 9th week after hindlimb ischemia model operation.

2020-06-10 | GSE152139 | GEO

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