DNA microarray analysis of gene expression in endothelial cells in response to 24-h shear stress

Chen, Benjamin P.C.; Li, Yi Shuan; Zhao, Yihua; Chen, Kuang Den; Li, Song; Lao, Jianmin; Yuan, Suli; Shyy, John Y.‐J.; Chien, Shu

doi:10.1152/physiolgenomics.2001.7.1.55

Cited by 217 publications

(152 citation statements)

References 51 publications

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“…There have been many studies on the effects of different flow patterns on EC gene expression at the mRNA level (34)(35)(36). Following the recent discovery that miRs provide a powerful mechanism for posttranscriptional control of gene expression and that they are involved in many biological processes, it is logical and timely to investigate the role of miRs in the laminar shear-induced antiproliferative action on ECs.…”

Section: Discussionmentioning

confidence: 99%

Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth

Wang

Garmire

Young

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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158

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MicroRNAs (miRs) can regulate many cellular functions, but their roles in regulating responses of vascular endothelial cells (ECs) to mechanical stimuli remain unexplored. We hypothesize that the physiological responses of ECs are regulated by not only mRNA and protein signaling networks, but also expression of the corresponding miRs. EC growth arrest induced by pulsatile shear (PS) flow is an important feature for flow regulation of ECs. miR profiling showed that 21 miRs are differentially expressed (8 up-and 13 downregulated) in response to 24-h PS as compared to static condition (ST). The mRNA expression profile indicates EC growth arrest under 24-h PS. Analysis of differentially expressed miRs yielded 68 predicted mRNA targets that overlapped with results of microarray mRNA profiling. Functional analysis of miR profile indicates that the cell cycle network is highly regulated. The upregulation of miR-23b and miR-27b was found to correlate with the PS-induced EC growth arrest. Inhibition of miR-23b using antagomir-23b oligonucleotide (AM23b) reversed the PSinduced E2F1 reduction and retinoblastoma (Rb) hypophosphorylation and attenuated the PS-induced G1/G0 arrest. Antagomir AM27b regulated E2F1 expression, but did not affect Rb and growth arrest. Our findings indicate that PS suppresses EC proliferation through the regulation of miR-23b and provide insights into the role of miRs in mechanotransduction.cell cycle | shear | bioinformatics | gene regulation | mechanotransduction H emodynamic forces, e.g., stretch and shear stress, act constantly on the vascular endothelial cells (ECs) to modulate EC signaling, gene expression, and physiological functions (1). Atherosclerotic lesions in the arterial tree are found mainly at branch points, where blood flow is disturbed with a limited forwarding direction, but are generally spared at the straight parts of the arterial tree, where the flow is laminar with a large forwarding direction (2). Exposure of ECs to 24 h of steady laminar shear flow at 12 dyn/cm 2 (approximating the hemodynamic force in straight parts of arteries) leads to antiproliferative (3) and antiinflammatory (4) responses. In contrast, ECs exposed to disturbed flow, mimicking the hemodynamic force at branch points, exhibit opposite responses (5, 6). The laminar shear-induced EC growth arrest involves the expression of CDK inhibitors (e.g., p21 cip , p27 kip ), tumor suppressor p53, and retinoblastoma (Rb) hypophosphorylation (3, 7). Whereas there is considerable knowledge on mechanotransduction at protein and mRNA levels, there is little information on the role of microRNAs (miRs) in this process.miRs are small noncoding RNAs (∼21-25 nucleotides) that regulate gene expression by binding to target mRNAs to cause their degradation or translational repression (8). It is estimated that miRs regulate ∼30% of human protein-coding genes. More than 800 miRs have been identified in the human genome and registered in the Sanger miRBase. These small RNAs provide a powerful mechanism for posttranscriptional cont...

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Section: Discussionmentioning

confidence: 99%

Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth

Wang

Garmire

Young

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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158

132

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“…DNA microarray technology is a powerful tool for rapid, comprehensive, and quantitative analysis of gene expression profiles of normal and disease states (Chen et al, 2001). This technology has been successfully applied to identify potential target genes for pulmonary hypoxia (Truog et al, 2008;Zhou et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Expression profiling analysis of hypoxic pulmonary disease

Zhou

Wang²,

Song³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Exposure of humans to low levels of environmental oxygen results in alveolar hypoxia and normally causes chronic pulmonary hypertension and morphological alterations of precapillary pulmonary vessels. In this study, the microarray dataset GSE11341 was used to identify potential differentially expressed genes related with human lung microvascular endothelial cell hypoxia. In addition, gene ontology term enrichment analysis was performed to explore their underlying functions. In addition, we also investigated the small molecules by comparing with the Connectivity Map. We found that hypoxia samples of 3, 24, and 48 h relative to 0 h displayed 22, 21, and 29 differentially expressed genes, respectively. Among them, six genes (ADM, HMOX1, VEGFA, EGLN3, APOLD1, and ANGPTL4) were closely related to pulmonary microvascular endothelial cell hypoxia response. Three drugs (pindolol, sulfapyridine, and ciclopirox) were selected as candidates to treat hypoxia-related pulmonary diseases. In conclusion, our results provide some underlying drug targets for treatment of hypoxic pulmonary patients.

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“…Thus, gene misuse/abuse is more deceptive and even more difficult to detect than conventional drug abuse [5,6]. The changes in certain genes detected via microarray analysis might decipher the molecular mechanisms involved in physiological and pathological processes in various cells or tissues [10,11]. Such genes could serve as surrogate markers for the induced modifications, and could obviate the need for muscle biopsies.…”

Section: Introductionmentioning

confidence: 99%

A microarray gene analysis of peripheral whole blood in normal adult male rats after long-term GH gene therapy

Qin

Tian

2010

Cellular and Molecular Biology Letters

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The main aims of this study were to determine the effects of GH gene abuse/misuse in normal animals and to discover genes that could be used as candidate biomarkers for the detection of GH gene therapy abuse/misuse in humans. We determined the global gene expression profile of peripheral whole blood from normal adult male rats after long-term GH gene therapy using CapitalBio 27 K Rat Genome Oligo Arrays. Sixty one genes were found to be differentially expressed in GH gene-treated rats 24 weeks after receiving GH gene therapy, at a two-fold higher or lower level compared to the empty vector group (p < 0.05). These genes were mainly associated with angiogenesis, oncogenesis, apoptosis, immune networks, signaling pathways, general metabolism, type I diabetes mellitus, carbon fixation, cell adhesion molecules, and cytokine-cytokine receptor interaction. The results imply that exogenous GH gene expression in normal subjects is likely to induce cellular changes in the metabolism, signal pathways and immunity. A real-time qRT-PCR analysis of a selection of the genes confirmed the microarray data. Eight differently expressed genes were selected as candidate biomarkers from among these 61 genes. These 8 showed five-fold higher or lower expression levels after the GH gene transduction (p < 0.05). They were then validated in real-time PCR experiments using 15 single-treated blood samples and 10 control blood samples. In summary, we detected the gene expression profiles of rat peripheral whole blood after long-term GH gene therapy and screened eight genes as candidate biomarkers based on the microarray data. This will contribute to an increased mechanistic understanding of the effects of chronic GH gene therapy abuse/misuse in normal subjects.

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DNA microarray analysis of gene expression in endothelial cells in response to 24-h shear stress

Cited by 217 publications

References 51 publications

Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth

Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth

Expression profiling analysis of hypoxic pulmonary disease

A microarray gene analysis of peripheral whole blood in normal adult male rats after long-term GH gene therapy

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