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Transcriptomic profile analysis of brain microvascular pericytes in spontaneously hypertensive rats by RNA-Seq.

ABSTRACT: BACKGROUND:Changes in the structure and function of micro-vessels is the pathogenic basis of organ damage in cardiovascular and cerebrovascular diseases. Microcirculation is primarily affected in hypertension, resulting in increased vascular resistance. Pericytes are contractile cells that are embedded in the basement membrane of capillaries, and regulate endothelial cell membrane maturation, capillary blood flow, cell debris removal, and stability of endothelial cells. However, the exact role of brain microvascular pericytes in the pathogenesis of hypertension has not been elucidated. METHODS:Brain microvascular pericytes were isolated from spontaneously hypertensive rats (SHR) and wild type Wistar Kyoto (WKY) rats. The transcriptomes of SHR and WKY pericytes were analyzed by RNA-Seq, and the differentially expressed genes (DEGs) were screened by Ballgown, and Student's t test was used to be used to compare differences between groups. DAVID was used for the GO-enrichment analysis and KEGG pathway analysis of the DEGs, and an interaction network between the significant signaling pathways and DEGs was constructed. RESULTS:A total of 1356 DEGs were identified between the WKY and the SHR group pericytes (P value < 0.05, Fold change > 1.5), of which 733 were upregulated and 623 downregulated. The genes with greatest betweenness centrality values were Itgb1, Vcam-1 and MMP-9. Based on KEGG analysis, 34 interacting signaling pathways and 43 interacting genes were screened, and MAPK, p53, Wnt, Jak-STAT, TGF-beta, VEGF and PPAR signaling pathways were the key nodes. CONCLUSIONS:Several DEGs and signaling pathways were identified in the brain microvascular pericytes of SHR rats compared to the WKY rats. Our findings will lay the foundation to study the role of brain microvascular pericytes in the development of spontaneous hypertension.

SUBMITTER: Yuan X

PROVIDER: S-EPMC6129547 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Transcriptomic profile analysis of brain microvascular pericytes in spontaneously hypertensive rats by RNA-Seq.

Yuan Xiaochen X Wu Qingbin Q Liu Xueting X Zhang Honggang H Xiu Ruijuan R

American journal of translational research 20180815 8

<h4>Background</h4>Changes in the structure and function of micro-vessels is the pathogenic basis of organ damage in cardiovascular and cerebrovascular diseases. Microcirculation is primarily affected in hypertension, resulting in increased vascular resistance. Pericytes are contractile cells that are embedded in the basement membrane of capillaries, and regulate endothelial cell membrane maturation, capillary blood flow, cell debris removal, and stability of endothelial cells. However, the exac ...[more]

PMID: 30210677

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Project description:BackgroundHypertension is an important risk factor for cerebrovascular disease, including stroke and dementia. Both in humans and animal models of hypertension, neuropathological features such as brain atrophy and oedema have been reported. We hypothesised that cerebrovascular damage resulting from chronic hypertension would manifest itself in a more permeable blood-brain barrier and blood-cerebrospinal fluid barrier. In addition, more leaky barriers could potentially contribute to an enhanced interstitial fluid and cerebrospinal fluid formation, which could, in turn, lead to an elevated intracranial pressure.MethodsTo study this, we monitored intracranial pressure and estimated the cerebrospinal fluid production rate in spontaneously hypertensive (SHR) and normotensive rats (Wistar Kyoto, WKY) at 10 months of age. Blood-brain barrier and blood-cerebrospinal fluid barrier integrity was determined by measuring the leakage of fluorescein from the circulation into the brain and cerebrospinal fluid compartment. Prior to sacrifice, a fluorescently labelled lectin was injected into the bloodstream to visualise the vasculature and subsequently study a number of specific vascular characteristics in six different brain regions.ResultsBlood and brain fluorescein levels were not different between the two strains. However, cerebrospinal fluid fluorescein levels were significantly lower in SHR. This could not be explained by a difference in cerebrospinal fluid turnover, as cerebrospinal fluid production rates were similar in SHR and WKY, but may relate to a larger ventricular volume in the hypertensive strain. Also, intracranial pressure was not different between SHR and WKY. Morphometric analysis of capillary volume fraction, number of branches, capillary diameter, and total length did not reveal differences between SHR and WKY.ConclusionIn conclusion, we found no evidence for blood-brain barrier or blood-cerebrospinal fluid barrier leakage to a small solute, fluorescein, in rats with established hypertension.

Project description:Background: Circular RNAs (circRNAs), as a kind of endogenous non-coding RNA, have been implicated in ischemic heart diseases and vascular diseases. Based on theirs high stability with a closed loop structure, circRNAs function as a sponge and bind specific miRNAs to exert inhibitory effects in heart and vasculature, thereby regulating their target gene and protein expression, via competitive endogenous RNA (ceRNA) mechanism. However, the exact roles and underlying mechanisms of circRNAs in hypertension and related cardiovascular diseases remain largely unknown. Methods and Results: High-throughput RNA sequencing (RNA-seq) was used to analyze the differentially expressed (DE) circRNAs in aortic vascular tissues of spontaneously hypertensive rats (SHR). Compared with the Wistar-Kyoto (WKY) rats, there were marked increases in the levels of systolic blood pressure, diastolic blood pressure and mean blood pressure in SHR under awake conditions via the tail-cuff methodology. Totally, compared with WKY rats, 485 DE circRNAs were found in aortic vascular tissues of SHR with 279 up-regulated circRNAs and 206 down-regulated circRNAs. Furthermore, circRNA-target microRNAs (miRNAs) and the target messenger RNAs (mRNAs) of miRNAs were predicted by the miRanda and Targetscan softwares, respectively. Additionally, real-time RT-PCR analysis verified that downregulation of rno_circRNA_0009197, and upregulation of rno_circRNA_0005818, rno_circRNA_0005304, rno_circRNA_0005506, and rno_circRNA_0009301 were observed in aorta of SHR when compared with that of WKY rats. Then, the potential ceRNA regulatory mechanism was constructed via integrating 5 validated circRNAs, 31 predicted miRNAs, and 266 target mRNAs. More importantly, three hub genes (NOTCH1, FOXO3, and STAT3) were recognized according to PPI network and three promising circRNA-miRNA-mRNA regulatory axes were found in hypertensive rat aorta, including rno_circRNA_0005818/miR-615/NOTCH1, rno_circRNA_0009197/ miR-509-5p/FOXO3, and rno_circRNA_0005818/miR-10b-5p/STAT3, respectively. Conclusions: Our results demonstrated for the first time that circRNAs are expressed aberrantly in aortic vascular tissues of hypertensive rats and may serve as a sponge linking with relevant miRNAs participating in pathogenesis of hypertension and related ischemic heart diseases via the circRNA-miRNA-mRNA ceRNAnetwork mechanism.

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Transcriptomic profile analysis of brain microvascular pericytes in spontaneously hypertensive rats by RNA-Seq.

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Transcriptomic profile analysis of brain microvascular pericytes in spontaneously hypertensive rats by RNA-Seq.

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