MiRNA Profiling of Exosomes from Spontaneous Hypertensive Rats by Next-Generation Sequencing
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ABSTRACT: The role and miRNA expression profile of exosomes in hypertension remain largely unknown, therefore, next generation sequencing was used to define the miRNA expression profile of plasma exosomes in spontaneously hypertensive rats (SHRs), the most widely used animal model of human essential hypertension, and their controls, normotensive Wistar-Kyoto rats (WKYs). Results revealed that percentages of miRNA in the total small RNA isolated from WKYs and SHRs were not significantly different. Twenty-seven miRNAs were significantly differentially expressed (DE) between WKY and SHR exosomes, among which 23 were upregulated and 4 were downregulated in SHR exosomes compared with WKY exosomes. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis of top 10 DE miRNAs identified hypertension-specific target genes/signaling pathways. In conclusion, our findings indicate the selective packing of miRNA cargoes into exosomes under hypertensive status, while facilitating the development of potential targets for the diagnosis, prevention and treatment of hypertension.
Project description:The objective of this study was to characterize differences in the global gene expression profiles of spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) at different stages of hypertension. Using RNA isolated from liver of SHR and WKY rats, we compared the gene expression profiles by microarrays. Differential gene expression was detected in the liver of SHR rats compared to WKY control rats, possibly contributing to hypertension
Project description:Hypertension is a multifactor disease that possibly involves alterations in gene expression in hypertensive relative to normotensive subjects that are largely unknown. In this study we used high-density oligoarrays to compare gene expression profiles in cultured neurons and glia from pons and medulla oblongata of newborn spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats, a widely documented animal model of hypertension. We found 358 genes differentially expressed between SHR and WKY brainstem cells that preferentially map to 24 metabolic/signaling pathways. Some of the pathways and regulated genes identified herein are obviously related to blood pressure regulation; however there are several genes differentially expressed in SHR not yet associated to hypertension or participating in blood pressure regulation. These constitute a rich resource for the identification and characterization of novel genes involved in hypertension development, or associated to phenotypical differences observed in SHR relative to WKI. In conclusion, this study describes for the first time the gene profiling pattern of brainstem cells from SHR and WKY rats, which opens up new possibilities and strategies of investigation and possible therapeutics to hypertension, as well as for the understanding of the brain contribution in this pathology. Keywords: Gene expression profiling of cultured cells from brainstem of spontaneously hypertensive and normotensive Wistar Kyoto rats
Project description:We investigated morphometric structure and gene expression by microarray analysis in a small diameter artery, branch of the saphenous artery (a resistance artery), in representative models of renin-angiotensin system (RAS)-dependent and glucocorticoid hypertension, using the spontaneously hypertensive rat (SHR) and adrenocorticotropic hormone (ACTH)-induced hypertensive rat, respectively. Sixteen-week-old male Wistar-Kyoto (WKY) and age-matched spontaneously hypertensive rats (SHR) were used. Keywords: Comparison of global gene expression in resistance arteries of normotensive and genetically hypertensive rats and ACTH-treated rats.
Project description:Before morphological changes at the early stage of hypertension, how overloaded hypertension influences the transcriptomic profile of the left atrium remains unclear, therefore, RNA-sequencing was performed to define the RNA expressing profiles of left atrium in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) as a control group. At the same time, we compared the RNA expressing profiles changes in ARB-treated (valsartan, 30mg/kg/d) and ARNI-treated (sacubitril/valsartan, 60mg/kg/d) SHR to reveal the distinct effects on the left atrium. A total of 1558 differentially expressed genes were found in the left atrium between WKY rats and SHRs. Bioinformatics analysis revealed that these mRNAs could regulate the upstream pathways in atrial remodeling through atrial fibrosis, inflammation, electrical remodeling, and cardiac metabolism. The regulated transcripts of left atrial tissue in both the ARB-treated and ARNI-treated groups were related to metabolism. Compared with ARB, transcripts in ARNI-treated rats were mapped to the cGMP-PKG signaling pathway.
Project description:Left ventricle gene expression was analyzed in three models of hypertension in order to clarify the molecular mechanisms associated with left ventricular hypertrophy. Transgenic heterozygous TGR(mRen2)27 rats, overexpressing the mouse renin gene, and their littermate negative controls, spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY), and Lyon hypertensive rats (LH) and their normotensive controls (LL) were included in the study.
Project description:We investigated morphometric structure and gene expression by microarray analysis in a small diameter artery, branch of the saphenous artery (a resistance artery), in representative models of renin-angiotensin system (RAS)-dependent and glucocorticoid hypertension, using the spontaneously hypertensive rat (SHR) and adrenocorticotropic hormone (ACTH)-induced hypertensive rat, respectively. Sixteen-week-old male Wistar-Kyoto (WKY) and age-matched spontaneously hypertensive rats (SHR) were used. Experiment Overall Design: There were 3 experimental groups: Group 1: 16-week male Wistar-Kyoto rats; Group 2: 16-week male Wistar-Kyoto rats treated with ACTH (0.1mg/kg/day) subcutaneously, for 4 weeks prior to sampling (i.e. during weeks 12-16 of life) ; Group3: 16-week male SHR (spontaneously hypertensive) rats. There were 3 replicate hybridizations in each experimental group. Due to the low yield of total RNA obtained from the arterial sections, each replicate was composed of RNA pooled from 2-3 different rats.
Project description:Spontaneously hypertensive rats (SHR) have been used frequently as a model for human essential hypertension. However, both the SHR and its normotensive control, the Wistar Kyoto rat (WKY), consist of genetically different sublines. We tested the hypothesis that discrepant data in literature regarding the pathophysiology of vascular remodeling in hypertension result from the use of different rat sublines. Using micro-arrays, we studied miRNA and mRNA expression in resistance arteries of WKY and SHR from three different sources, at 6 weeks and 5 months of age. Both WKY and SHR showed an age-related expression pattern that involved many genes related to the extracellular matrix. In SHR, this pattern was more extensive and included a specific increase in miR132-3p, and type III deiodinase. Direct comparison of WKY to SHR also yielded differences in expression, including thrombospondin 4. Heterogeneity in gene expression among sublines was associated with differences in blood pressure, body weight, vascular remodeling, endothelial function, and vessel ultrastructure. Common features in vessels from SHR were an increase in wall thickness, wall-to-lumen ratio, and internal elastic lamina thickness. These results indicate that endothelial dysfunction, vascular stiffening, and inward remodeling of small arteries are not common features of hypertension, but are subline-dependent. Relatively minor differences in genetic background associate with different types of vascular remodeling in hypertensive rats. The clinical implication of this study is that more research into personalized treatment in hypertension is warranted.
Project description:Spontaneously hypertensive rats (SHR) have been used frequently as a model for human essential hypertension. However, both the SHR and its normotensive control, the Wistar Kyoto rat (WKY), consist of genetically different sublines. We tested the hypothesis that discrepant data in literature regarding the pathophysiology of vascular remodeling in hypertension result from the use of different rat sublines. Using micro-arrays, we studied miRNA and mRNA expression in resistance arteries of WKY and SHR from three different sources, at 6 weeks and 5 months of age. Both WKY and SHR showed an age-related expression pattern that involved many genes related to the extracellular matrix. In SHR, this pattern was more extensive and included a specific increase in miR132-3p, and type III deiodinase. Direct comparison of WKY to SHR also yielded differences in expression, including thrombospondin 4. Heterogeneity in gene expression among sublines was associated with differences in blood pressure, body weight, vascular remodeling, endothelial function, and vessel ultrastructure. Common features in vessels from SHR were an increase in wall thickness, wall-to-lumen ratio, and internal elastic lamina thickness. These results indicate that endothelial dysfunction, vascular stiffening, and inward remodeling of small arteries are not common features of hypertension, but are subline-dependent. Relatively minor differences in genetic background associate with different types of vascular remodeling in hypertensive rats. The clinical implication of this study is that more research into personalized treatment in hypertension is warranted.
Project description:Male SHRs and normotensive Wistar-Kyoto(WKY) rats were purchased from Vital River (Vital River Laboratory Animal Technology Co., Ltd, Beijing, China). Briefly, eightteen SHRs aged seven to eight weeks old were randomly assigned to one of three groups: water group (drinking tap water), water containing 333 mg/L or 1g/L TMAO group (TMAO, product number: T1362, Tokyo Chemical Industry, Japan). Six WKY rats of the same age were used as normotensive controls. In this study, WKY rats (n=6), SHR (n=6), and SHR treated with 1g/L TMAO (n=6) were uesd for experiments.
Project description:Our previous findings suggest that the nucleus of the solitary tract (NTS), a pivotal region for regulating the set-point of arterial pressure, exhibits abnormal inflammation in pre-hypertensive and spontaneously hypertensive rats (SHRs) together with elevated anti-apoptotic and low apoptotic factor levels compared with that of normotensive Wistar–Kyoto (WKY) rats. Whether this chronic condition affects neuronal growth and plasticity in the NTS remains unknown. To unveil the characteristics of the neurodevelopmental environment in the NTS of hypertensive rats, we investigated the gene expression profile of neurotrophins and their receptors in SHRs compared to that of normotensive rat WKY.