Rat hindlimb arteries: Shunt versus Control
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE16359 | GEO | 2010/05/26
SECONDARY ACCESSION(S): PRJNA115315
REPOSITORIES: GEO
Similar Datasets
Project description:Arterial occlusive diseases are major causes of morbidity and mortality. Blood flow to the affected tissue must be restored quickly if viability and function are to be preserved. Collaterals are artery-to-artery or arteriole-to-arteriole interconnections that can bypass an occlusion by providing an alternative route for blood flow to the affected tissue. The increased flow and sheer stress initiate processes that result in the remodeling (arteriogenesis) of these vessels into efficient conductance arteries. Here we report that the mixed-lineage kinase (MLK) pathway activates cJun NH2-terminal kinase (JNK) in endothelial cells. Disruption of Mlk2/3 or Jnk1/2 genes caused severe blockade of blood flow and failure to recover in the femoral artery ligation model of hindlimb ischemia because of abnormal collateral arteries. We show that the MLK-JNK pathway is essential for patterning and maturation of collateral arteries during development, but this pathway is not required for angiogenesis or arteriogenesis in adults. JNK in endothelial cells promotes Delta-like 4-induced Notch signaling and suppresses excessive sprouting angiogenesis during development. This function of the MLK-JNK pathway contributes to normal formation of native collateral arteries. The MLK-JNK pathway is therefore a key regulatory mechanism for vascular development. These data highlight the crucial importance of the collateral circulation in the response to arterial occlusive diseases. RNA-seq analysis of mouse lung endothelial cells (MLEC) of the following genotypes Cdh5-Cre+ Jnk1+/+ Jnk2+/+ Jnk3-/-(ECtrl), Cdh5-Cre- Jnk1LoxP/LoxP Jnk2LoxP/LoxP Jnk3-/- (EfCtrl), and Cdh5-Cre+ Jnk1LoxP/LoxP Jnk2LoxP/LoxP Jnk3-/- (E3KO). Three separate samples from mouse lung endothelial cells of each genotype were analyzed.
2016-08-09 | E-GEOD-71159 | biostudies-arrayexpress
Project description:Arterial occlusive diseases are major causes of morbidity and mortality. Blood flow to the affected tissue must be restored quickly if viability and function are to be preserved. Collaterals are artery-to-artery or arteriole-to-arteriole interconnections that can bypass an occlusion by providing an alternative route for blood flow to the affected tissue. The increased flow and sheer stress initiate processes that result in the remodeling (arteriogenesis) of these vessels into efficient conductance arteries. Here we report that the mixed-lineage kinase (MLK) pathway activates cJun NH2-terminal kinase (JNK) in endothelial cells. Disruption of Mlk2/3 or Jnk1/2 genes caused severe blockade of blood flow and failure to recover in the femoral artery ligation model of hindlimb ischemia because of abnormal collateral arteries. We show that the MLK-JNK pathway is essential for patterning and maturation of collateral arteries during development, but this pathway is not required for angiogenesis or arteriogenesis in adults. JNK in endothelial cells promotes Delta-like 4-induced Notch signaling and suppresses excessive sprouting angiogenesis during development. This function of the MLK-JNK pathway contributes to normal formation of native collateral arteries. The MLK-JNK pathway is therefore a key regulatory mechanism for vascular development. These data highlight the crucial importance of the collateral circulation in the response to arterial occlusive diseases.
2016-08-09 | GSE71159 | GEO
Project description:This study aims at a comprehensive understanding of the genomic program activated during early-phase of collateral vessel growth in a rat model for cerebral adaptive arteriogenesis (3-VO). While arteriogenesis constitutes a promising therapeutic concept for cerebrovascular ischemia, genomic profiles essential for therapeutic target identification were analysed solely for collateral arteries of the heart and periphery. Despite challenging anatomical conditions of the brain the 3-VO model allows identification of differentially expressed genes during adaptive cerebral arteriogenesis by selective removal of the posterior cerebral artery (PCA). Keywords: early response time course, selective collateral growth, brain
2008-09-01 | GSE6189 | GEO
Project description:Analysis of global gene expression in mesenteric control and collateral arteries was used to investigate potential molecules, pathways and mechanisms responsible for impaired collateral growth in the Spontaneously Hypertensive rat (SHR). A fundamental difference was observed in the overall gene expression pattern in SHR vs. Wistar Kyoto (WKY) collaterals (only 6% of the genes altered in collaterals were similar). IPA analysis identified major differences between WKY and SHR in networks and biological functions related to cell growth and proliferation and gene expression. Canonical pathways identified by IPA in WKY but not SHR included nitric oxide and renin angiotensin system signaling. The angiotensin type 1 receptor (AT1R) exhibited up-regulation in WKY collaterals, but down-regulation in SHR; pharmacological blockade of the AT1R with losartan prevented collateral luminal expansion in WKY. In SHR control arteries, several mechano-sensitive and redox-dependent transcription regulators were down-regulated including Jun (-5.2X, P=0.02), Egr-1 (-4.1X, P=0.01), and NFkB1 (-1.95X, P=0.04). Predicted binding sites for NFkB and AP-1 were present in the genes altered in WKY but not SHR collaterals. Immunostaining demonstrated increased NFkB nuclear translocation in WKY but not SHR collaterals, and in collaterals of SHR treated with apocynin to restore a normal redox status. Based upon these results, we propose redox-dependent modulation of mechano-sensitive transcription factors as a mechanism to explain, at least in part, the fundamental differences in collateral gene expression between WKY and SHR and the impairment of collateral growth during chronic oxidative stress. Key words: arteriogenesis, microarray analysis, peripheral vascular disease, gene expression
2010-12-15 | GSE19524 | GEO
Project description:A porcine microarray study of right ventricular failure due to coronary artery ligation of the right ventricular free wall and subsequent treatment of right ventricular failure by volume unloading using a shunt between superior vena cava and the pulmonary artery (Glenn-shunt) 1. Surgical preparation with a 12 mm graft between superior vena cava and pulmonary artery, the graft is then clamped - Baseline sample using a biopsy needle. 2. After surgical preparation the coronary arteries of the right ventricular free wall are ligated, then heart failure develops over 120 minutes - Failure sample using a biopsy needle. 3. The shunt is then opened and the superior vena cava closed between the shunt and right atrium, diverting the blood from superior vena cava through the shunt for a period of 15 minutes partially unloading the right ventricle - Shunt sample using a biopsy needle. A series of six pigs, three samples from each animal: baseline, failure and shunt/treatment.
2011-08-23 | E-GEOD-31619 | biostudies-arrayexpress
Project description:This study characterizes the response of primary human endothelial cells (human umbilical vein endothelial cells, HUVECs) to the relative shear stress changes that occur during the initiation of arteriogenesis at the entrance regions to a collateral artery network. HUVECs were preconditioned to a baseline level of unidirectional shear of 15 dynes/cm2 for 24 hours. After 24 hours preconditioning, HUVECs were subjected to an arteriogenic stimulus that mimics the shear stress changes observed in the opposing entrance regions into a collateral artery network. The arteriogenic stimulus consisted of a 100% step wise increase in shear stress magnitude to a unidirectional 30 dynes/cm2 in either the same or opposite direction of the preconditioned shear stress. This simulates either the feeding entrance to the collateral artery circuit or the region that drains into the vasculature downstream of an obstruction in a major artery, respectively. In vivo analysis of collateral growth in the mouse hindlimb showed enhanced outward remodeling in the re-entrant (direction reversing) region that reconnects to the downstream arterial tree, suggesting reversal of shear stress direction as a key enhancer of arteriogenesis. Transcriptional profiling using microarray techniques identified that the reversal of shear stress direction, but not an increase in shear stress alone, yielded a broad-based enhancement of the mechanotransduction pathways necessary for the induction of arteriogenesis. Human umbilical vein endothelial cells (HUVECs) were preconditioned to a unidirectional clockwise shear stress of 15 dynes/cm2 for 24 hours. An acute increase in shear stress magnitude to 30 dynes/cm2 in either a clockwise (non-reversed) or counter-clockwise (reversed) direction was applied for 6 hours. An additional preconditioned control culture was maintained under a unidirectional clockwise shear stress of 15 dynes/cm2 and harvested at the same time point, 6 hours post-conditioning. Each condition of reversed, non-reversed, and control was performed in tandem from the same starting cell culture as one replicate. The total experiment consisted of four replicates. Gene transcription was then assessed using microarray expression analysis.
2016-04-01 | E-GEOD-46248 | biostudies-arrayexpress
Project description:This study characterizes the response of primary human endothelial cells (human umbilical vein endothelial cells, HUVECs) to the relative shear stress changes that occur during the initiation of arteriogenesis at the entrance regions to a collateral artery network. HUVECs were preconditioned to a baseline level of unidirectional shear of 15 dynes/cm2 for 24 hours. After 24 hours preconditioning, HUVECs were subjected to an arteriogenic stimulus that mimics the shear stress changes observed in the opposing entrance regions into a collateral artery network. The arteriogenic stimulus consisted of a 100% step wise increase in shear stress magnitude to a unidirectional 30 dynes/cm2 in either the same or opposite direction of the preconditioned shear stress. This simulates either the feeding entrance to the collateral artery circuit or the region that drains into the vasculature downstream of an obstruction in a major artery, respectively. In vivo analysis of collateral growth in the mouse hindlimb showed enhanced outward remodeling in the re-entrant (direction reversing) region that reconnects to the downstream arterial tree, suggesting reversal of shear stress direction as a key enhancer of arteriogenesis. Transcriptional profiling using microarray techniques identified that the reversal of shear stress direction, but not an increase in shear stress alone, yielded a broad-based enhancement of the mechanotransduction pathways necessary for the induction of arteriogenesis.
2016-04-01 | GSE46248 | GEO
Project description:Background: Collateral artery growth, also termed arteriogenesis, occurs upon narrowing or occlusion of a major artery. To date, attempts to stimulate arteriogenesis in patients for therapeutic purposes have not been successful. Experimental models showed that circulating cells orchestrate arteriogenesis. In humans, a large heterogeneity exists in the arteriogenic response. We hypothesized that good arteriogenic responders (GARs) and bad arteriogenic responders (BARs) differ in gene expression profiles of circulating cells, thereby disclosing potential new therapeutic strategies for the stimulation of arteriogenesis. Methods: A total of 45 patients scheduled for percutaneous coronary intervention (PCI) for single-vessel coronary artery disease underwent intracoronary measurements of collateral flow index (CFI) to distinguish between GARs (CFI>0.21) and BARs (CFI≤0.21). Monocytes and CD34+ stem cells were collected from peripheral blood. A fraction of monocytes was further processed to obtain stimulated monocytes and macrophages. Whole genome transcriptome analysis was performed on all four cell types. Results: LPS-stimulated monocytes showed 244 genes differentially expressed (false discovery rate < 0.05) between GARs and BARs. Macrophage gene expression correlated with stimulated monocytes, while resting monocytes and stem cells revealed no differential gene expression. Stimulated monocytes from GARs showed a strongly attenuated response in several interferon- and apoptosis-related genes, which was corroborated at the protein level. Conclusions Circulating cells from GARs and BARs distinctively differ in their gene expression profiles upon stimulation. The reduced expression of interferon and apoptosis genes in GARs may lead to novel therapeutic approaches for the stimulation of collateral artery growth. Keywords: disease state analysis, stress response analysis, natural defense mechanism analysis
2008-04-17 | GSE7547 | GEO
Project description:Evaluation of transcriptional regulation in Coronary artery disease patients with and without collateral artery vessels.
2006-03-10 | E-MEXP-564 | biostudies-arrayexpress
Project description:Genomic analysis of control and collateral arteries was used to investigate mechanisms responsible for impaired collateral growth in the Spontaneously Hypertensive rat, an animal model of essential hypertension with increased oxidative and nitrosative stress and metabolic abnormalities. A fundamental difference was observed in the overall expression pattern in SHR vs WKY collaterals. Redox related genes with altered expression included cyba (the gene encoding p22phox), superoxide dismutase 3, and thioredoxin reductases 1 and 2. Cystatin C, hevin, angiotensinogen, and the angiotensin type 1b receptor (AT1bR) had altered collateral expression that was confirmed by RT-PCR. These molecules are known to have significant roles in other types of arterial remodeling. Of specific interest was the AT1bR which exhibited up-regulation in WKY collaterals, but down-regulation in SHR. A remarkable increase in AT1R protein was observed in WKY but not SHR collaterals. Pharmacological blockade of the AT1R with losartan prevented collateral luminal expansion in WKY. In SHR, captopril restored redox status assessed by cyba expression and nitric oxide concentration, prevented collateral AT1bR down-regulation and re-established the capacity for collateral growth. These results indicate that redox-status significantly alters flow-mediated transcriptional regulation and demonstrate that increased flow-related expression/activation of the AT1R is required for normal collateral luminal expansion but is altered by chronic oxidative and/or nitrosative stress in hypertensive rats. Keywords: gene expression two strains: two vessel types
2010-12-15 | E-GEOD-19524 | biostudies-arrayexpress