Mouse carotid artery ligation tissue about neointimal formation
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus
SUBMITTER: 
Ningning Liu
PROVIDER: PXD073903 | iProX | Sat Jan 31 00:00:00 GMT 2026
REPOSITORIES: iProX
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Project description:Recently, we showed that disturbed flow caused by a partial ligation ofmouse carotid artery rapidly induces atherosclerosis. Analysis of mechanosenstive microRNA in the mouse carotid endothelium. In this study, we examined the microRNAs that respond differentially to blood flow pattern in the mouse carotid endothelium. We surgically induced disturbed blood flow in the left common carotid cartery (LCA) using partial carotid ligation surgery while the right carotid artery was left undisturbed. The hypothesis tested here is that turbulent or disturbed blood flow across the left carotid artery endothelium will affect endothelial genes and microRNAS. Identifying flow-sensitive microRNAs will provide important information about how endothelium responds to d-flow and regulates endothelial function and progression of atherosclerosis. Deter- mining the functional importance of these novel mechanosensitive microRNAS may provide important insights into understanding vascular biology and atherosclerosis.
2014-01-13 | GSE52243 | GEO
Project description:Recently, we showed that disturbed flow caused by a partial ligation ofmouse carotid artery rapidly induces atherosclerosis. Analysis of mechanosenstive microRNA in the mouse carotid endothelium. In this study, we examined the microRNAs that respond differentially to blood flow pattern in the mouse carotid endothelium. We surgically induced disturbed blood flow in the left common carotid cartery (LCA) using partial carotid ligation surgery while the right carotid artery was left undisturbed. The hypothesis tested here is that turbulent or disturbed blood flow across the left carotid artery endothelium will affect endothelial genes and microRNAS. Identifying flow-sensitive microRNAs will provide important information about how endothelium responds to d-flow and regulates endothelial function and progression of atherosclerosis. Deter- mining the functional importance of these novel mechanosensitive microRNAS may provide important insights into understanding vascular biology and atherosclerosis. We used 6- to 8-week-old male C57Bl/6 mice (The Jackson Laboratory) according to the approved Institutional Animal Care and Use Committee protocol by Emory University. Mice were subjected to partial carotid ligation surgery under anesthesia. Briefly, 3 of 4 caudal branches of LCA (left external carotid, internal carotid, and occipital artery) were ligated with 6-0 silk suture, although the superior thyroid artery was left intact. Development of low and oscillatory blood flow in the Left Carotid Artery of each mouse was determined by ultrasound measurements.
2014-01-13 | E-GEOD-52243 | biostudies-arrayexpress
Project description:Surgical interventions on blood vessels bear a risk for intimal hyperplasia and atherosclerosis as a consequence of injury. A specific feature of intimal hyperplasia is the loss of vascular smooth muscle cell (VSMC) differentiation gene expression. We hypothesized that immediate responses following injury induce vascular remodeling. To differentiate injury due to trauma, reperfusion and pressure changes we analyzed vascular responses to carotid artery bypass grafting in mice compared to transient ligation. As a control, the carotid artery was surgically laid open only. In both, bypass or ligation models, the inflammatory responses were transient, peaking after 6h, whereas the loss of VSMC differentiation gene expression persisted. Extended time kinetics showed that transient carotid artery ligation was sufficient to induce a persistent VSMC phenotype change throughout 28 days. Transient arterial ligation in ApoE knockout mice resulted in atherosclerosis in the transiently ligated vascular segment but not on the not-ligated contralateral side. The VSMC phenotype change could not be prevented by anti-TNF antibodies, Sorafenib, Cytosporone B or N-acetylcysteine treatment. Surgical interventions involving hypoxia/reperfusion are sufficient to induce VSMC phenotype changes and vascular remodeling. In situations of a perturbed lipid metabolism this bears the risk to precipitate atherosclerosis.
2018-09-06 | GSE119549 | GEO
Project description:Recently, we have shown that disturbed flow caused by partial ligation of mouse carotid artery rapidly induces endothelial dysfunction and atherosclerosis within two weeks. To understand the molecular mechanisms by which disturbed flow induces atherosclerosis, we carried out genome-wide microarray study using endothelial RNAs isolated from the flow-disturbed left and the contralateral right common carotid artery (LCA and RCA) in C57BL/6 mice. Total intimal RNAs were obtained from LCA and RCA at 12hr and at 48hr post-ligation. Intimal RNAs from three LCAs or RCAs were pooled to obtain ~30ng total RNA.
2011-03-10 | E-GEOD-20741 | biostudies-arrayexpress
Project description:Recently, we have shown that disturbed flow caused by partial ligation of mouse carotid artery rapidly induces endothelial dysfunction and atherosclerosis within two weeks. To understand the molecular mechanisms by which disturbed flow induces atherosclerosis, we carried out genome-wide microarray study using endothelial RNAs isolated from the flow-disturbed left and the contralateral right common carotid artery (LCA and RCA) in C57BL/6 mice.
2011-03-10 | GSE20741 | GEO
Project description:Acute vascular injury is an unwelcome consequence of invasive treatments designed to alleviate symptoms of vascular stenosis. Resulting fibrotic scarring and neointima formation may result in loss of lumen diameter and diminished vascular function. Understanding of the key phases of acute inflammation, resolution and remodeling has the potential to minimise unwanted effects on the vasculature and therefore improve patient outcomes. The cellular landscape of blood vessels is highly hetergeneous in nature, and therefore data at single-cell resolution is of high relevance to this problem. Herein, the cellularity of murine carotid artery tissue is described in a cell- and time-resolved manner. Single-cell RNA-sequencing of carotid tissue isolated at time-points ranging from uninjured vessel to 14 days post-injury enabled the recapitulation of all stages of vascular injury. In these data, a sub-population of smooth muscle cells which also arises in atherosclerosis and myocardial infarction was identified. So-called stem cells/endothelial cells/monocytes (SEM) cells are candidates for repopulating injured vessels, and were amongst the most proliferative cell clusters following wire-injury of the carotid artery. Transcriptional signatures reflecting SEM gene expression patterns could also be detected in bulk RNA-sequencing of neointimal tissue isolated by laser capture microdissection. These data indicate that phenotypic plasticity of smooth muscle cells is highly important to the progression of lumen loss following acute vascular insult.
2023-03-09 | GSE220779 | GEO
Project description:The proliferation and remodeling of vascular smooth muscle cells (VSMCs) is an important pathological event in atherosclerosis and restenosis. Here we report that microRNA-132 (miR-132) blocks vascular smooth muscle cells (VSMC) proliferation by inhibiting the expression of LRRFIP1 [leucine-rich repeat (in Flightless 1) interacting protein-1]. MicroRNA microarray revealed that miR-132 was upregulated in the rat carotid artery after catheter injury, which was further confirmed by quantitative real-time RT-PCR. Transfection of an miR-132 mimic significantly inhibited the proliferation of VSMCs, whereas transfection of an miR-132 antagomir increased it. Bioinformatics showed that LRRFIP1 is a target candidate of miR-132. miR-132 down-regulated luciferase activity driven by a vector containing the 3’-untranslated region of Lrrfip1 in a sequence-specific manner. LRRFIP1 induced VSMC proliferation. Immunohistochemical analysis revealed that Lrrfip1 was clearly expressed along with the basal laminar area of smooth muscle, and its expression pattern was disrupted 7 days after arterial injury LRRFIP1 mRNA was decreased 14 days after injury. Delivery of miR-132 to rat carotid artery attenuated neointimal proliferation in carotid artery injury models. Our results suggest that miR-132 is a novel regulator of VSMC proliferation that represses neointimal formation by inhibiting LRRFIP1 expression. Balloon injury was induced in the carotid arteries of male Sprague–Dawley rats weighing approximately 250 g. Total RNA were extracted from the arterial sections after 10 days. MicroRNA profile of the sample was compared with non-injured control.
2013-04-23 | E-GEOD-45433 | biostudies-arrayexpress
Project description:Atherosclerosis preferentially occurs in arterial regions of disturbed blood flow (d-flow), which alters gene expression, endothelial function, and atherosclerosis. Here, we show that d-flow regulates genome-wide DNA methylation patterns in a DNA methyltransferase (DNMT)-dependent manner. D-flow induced expression of DNMT1 in mouse arterial endothelium in vivo and in cultured endothelial cells by oscillatory shear (OS) in vitro. The DNMT inhibitor 5-Aza-2’deoxycytidine (5Aza) or DNMT1 siRNA significantly reduced OS-induced endothelial inflammation. Moreover, 5Aza reduced lesion formation in two ApoE-/- mouse atherosclerosis models. To identify the 5Aza mechanisms, we conducted two genome-wide studies: reduced representation bisulfite sequencing (RRBS) and microarray using endothelial-enriched gDNA and RNA, respectively, from the partially-ligated left carotid artery (LCA exposed to d-flow) and the right contralateral control (RCA) of mice treated with 5Aza or vehicle. Systems biological analyses using RRBS and transcriptome data revealed 11 mechanosensitive genes whose promoters were hypermethylated under d-flow conditions, but rescued by 5Aza treatment. Of those, the two transcription factors HoxA5 and Klf3 contain cAMP- response-elements, and their methylation status could serve as a mechanosensitive master switch in gene expression. Our results demonstrate that d-flow controls epigenomic DNA methylation patterns in a DNMT-dependent manner, which in turn alters endothelial gene expression and induces atherosclerosis. We used 6- to 8-week-old male C57Bl/6 mice (The Jackson Laboratory) according to the approved Institutional Animal Care and Use Committee protocol by Emory University. Mice were subjected to partial carotid ligation surgery under anesthesia. Briefly, 3 of 4 caudal branches of LCA (left external carotid, internal carotid, and occipital artery) were ligated with 6-0 silk suture, although the superior thyroid artery was left intact. Development of low and oscillatory blood flow in the Left Carotid Artery of each mouse was determined by ultrasound measurements. Each sample contained total RNA from 3 pooled RCAs or LCAs. We ran 3 samples of LCA, RCA, AzaLCA, and AzaRCA on 2 microarrays.
2014-03-25 | E-GEOD-56143 | biostudies-arrayexpress
Project description:Acute vascular injury is an unwelcome consequence of invasive treatments designed to alleviate symptoms of vascular stenosis. Resulting fibrotic scarring and neointima formation may result in loss of lumen diameter and diminished vascular function. Understanding of the key phases of acute inflammation, resolution and remodeling has the potential to minimise unwanted effects on the vasculature and therefore improve patient outcomes. The cellular landscape of blood vessels is highly hetergeneous in nature, and therefore data at single-cell resolution is of high relevance to this problem. Herein, the cellularity of murine carotid artery tissue is described in a cell- and time-resolved manner. Single-cell RNA-sequencing of carotid tissue isolated at time-points ranging from uninjured vessel to 14 days post-injury enabled the recapitulation of all stages of vascular injury. In these data, a sub-population of smooth muscle cells which also arises in atherosclerosis and myocardial infarction was identified. So-called stem cells/endothelial cells/monocytes (SEM) cells are candidates for repopulating injured vessels, and were amongst the most proliferative cell clusters following wire-injury of the carotid artery. Transcriptional signatures reflecting SEM gene expression patterns could also be detected in bulk RNA-sequencing of neointimal tissue isolated by laser capture microdissection. These data indicate that phenotypic plasticity of smooth muscle cells is highly important to the progression of lumen loss following acute vascular insult.
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