Temporal gene expression analysis of human coronary artery endothelial cells treated with simvastatin

Li Qin Zhang, Shwu Fan Ma, Dmitry Grigoryev, Tera L. Lavoie, Huiqing Xiao, Robert Setterquist, Hailong Li, Jeffrey Jacobson, Joe G N Garcia, Shui Qing Ye

Research output: Contribution to journalArticle

Abstract

Increasing evidence indicates that the beneficial "pleiotropic" effects of statins on clinical events involve nonlipid mechanisms including the modification of blood vessel endothelial cell function. However, the involved molecular events and pathways are not completely understood. In the present study, Affymetrix microarrays were used to monitor the temporal gene expression of human coronary artery endothelial cells (HCAEC) treated with simvastatin (Sim) to gain insight into statins' direct effects on the endothelial function. We isolated and labeled mRNA from HCAEC treated with Sim for 0, 3, 6, 12, 24, and 48 h and hybridized these samples to Affymetrix GeneChip HG-U95Av2 to analyze the temporal gene expression profile. Out of 12,625 genes present on the HG-U95Av2 GeneChip, expression of 5,432 genes was detected. There were 1,475 of 5,432 genes that displayed the differential expression compared to baseline (0 h). Fifty-four genes were upregulated (≤twofold) while 61 genes were downregulated (≥ twofold) at 24-48 h after the Sim treatment. Many new target genes and pathways modulated by Sim were uncovered. This study indicates that many aspects of the pleiotropic effect of Sim on the endothelial cell function can be mediated by transcriptional control. Physiological function of 22% of 115 differentially expressed genes in Sim-treated HCAEC are currently unknown. These newly identified genes could be useful for new mechanistic study and new therapeutic modalities. Expressions of 13 out of 18 genes (>70%) in the cell cycle/ proliferation control process were significantly inhibited by the Sim treatment. CDC25B and ITGB4 gene expressions were validated by RT-PCR and Western blotting. Sim's inhibitory effect of on HCAEC growth was confirmed by the measurement of [3H]thymidine incorporation into the DNA synthesis. Further in-depth analysis of this effect may shed light on molecular mechanisms of Sim's beneficial inhibition of neointima formation in the atherosclerotic artery stenosis.

Original languageEnglish (US)
Pages (from-to)229-239
Number of pages11
JournalGene Expression
Volume14
Issue number4
DOIs
StatePublished - 2008

Fingerprint

Simvastatin
Coronary Vessels
Endothelial Cells
Gene Expression
Genes
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Neointima
Cell Cycle Checkpoints
Transcriptome
Thymidine
Blood Vessels
Pathologic Constriction
Down-Regulation
Arteries
Western Blotting
Cell Proliferation
Polymerase Chain Reaction
Messenger RNA
DNA

Keywords

  • Coronary artery endothelial cells
  • Gene expression
  • Microarray
  • Simvastatin

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology

Cite this

Zhang, L. Q., Ma, S. F., Grigoryev, D., Lavoie, T. L., Xiao, H., Setterquist, R., ... Ye, S. Q. (2008). Temporal gene expression analysis of human coronary artery endothelial cells treated with simvastatin. Gene Expression, 14(4), 229-239. https://doi.org/10.3727/105221608786883834

Temporal gene expression analysis of human coronary artery endothelial cells treated with simvastatin. / Zhang, Li Qin; Ma, Shwu Fan; Grigoryev, Dmitry; Lavoie, Tera L.; Xiao, Huiqing; Setterquist, Robert; Li, Hailong; Jacobson, Jeffrey; Garcia, Joe G N; Ye, Shui Qing.

In: Gene Expression, Vol. 14, No. 4, 2008, p. 229-239.

Research output: Contribution to journalArticle

Zhang, LQ, Ma, SF, Grigoryev, D, Lavoie, TL, Xiao, H, Setterquist, R, Li, H, Jacobson, J, Garcia, JGN & Ye, SQ 2008, 'Temporal gene expression analysis of human coronary artery endothelial cells treated with simvastatin', Gene Expression, vol. 14, no. 4, pp. 229-239. https://doi.org/10.3727/105221608786883834
Zhang, Li Qin ; Ma, Shwu Fan ; Grigoryev, Dmitry ; Lavoie, Tera L. ; Xiao, Huiqing ; Setterquist, Robert ; Li, Hailong ; Jacobson, Jeffrey ; Garcia, Joe G N ; Ye, Shui Qing. / Temporal gene expression analysis of human coronary artery endothelial cells treated with simvastatin. In: Gene Expression. 2008 ; Vol. 14, No. 4. pp. 229-239.
@article{1b0342bc8a4141c5b86adcab5cefa8b1,
title = "Temporal gene expression analysis of human coronary artery endothelial cells treated with simvastatin",
abstract = "Increasing evidence indicates that the beneficial {"}pleiotropic{"} effects of statins on clinical events involve nonlipid mechanisms including the modification of blood vessel endothelial cell function. However, the involved molecular events and pathways are not completely understood. In the present study, Affymetrix microarrays were used to monitor the temporal gene expression of human coronary artery endothelial cells (HCAEC) treated with simvastatin (Sim) to gain insight into statins' direct effects on the endothelial function. We isolated and labeled mRNA from HCAEC treated with Sim for 0, 3, 6, 12, 24, and 48 h and hybridized these samples to Affymetrix GeneChip HG-U95Av2 to analyze the temporal gene expression profile. Out of 12,625 genes present on the HG-U95Av2 GeneChip, expression of 5,432 genes was detected. There were 1,475 of 5,432 genes that displayed the differential expression compared to baseline (0 h). Fifty-four genes were upregulated (≤twofold) while 61 genes were downregulated (≥ twofold) at 24-48 h after the Sim treatment. Many new target genes and pathways modulated by Sim were uncovered. This study indicates that many aspects of the pleiotropic effect of Sim on the endothelial cell function can be mediated by transcriptional control. Physiological function of 22{\%} of 115 differentially expressed genes in Sim-treated HCAEC are currently unknown. These newly identified genes could be useful for new mechanistic study and new therapeutic modalities. Expressions of 13 out of 18 genes (>70{\%}) in the cell cycle/ proliferation control process were significantly inhibited by the Sim treatment. CDC25B and ITGB4 gene expressions were validated by RT-PCR and Western blotting. Sim's inhibitory effect of on HCAEC growth was confirmed by the measurement of [3H]thymidine incorporation into the DNA synthesis. Further in-depth analysis of this effect may shed light on molecular mechanisms of Sim's beneficial inhibition of neointima formation in the atherosclerotic artery stenosis.",
keywords = "Coronary artery endothelial cells, Gene expression, Microarray, Simvastatin",
author = "Zhang, {Li Qin} and Ma, {Shwu Fan} and Dmitry Grigoryev and Lavoie, {Tera L.} and Huiqing Xiao and Robert Setterquist and Hailong Li and Jeffrey Jacobson and Garcia, {Joe G N} and Ye, {Shui Qing}",
year = "2008",
doi = "10.3727/105221608786883834",
language = "English (US)",
volume = "14",
pages = "229--239",
journal = "Gene Expression",
issn = "1052-2166",
publisher = "Cognizant Communication Corporation",
number = "4",

}

TY - JOUR

T1 - Temporal gene expression analysis of human coronary artery endothelial cells treated with simvastatin

AU - Zhang, Li Qin

AU - Ma, Shwu Fan

AU - Grigoryev, Dmitry

AU - Lavoie, Tera L.

AU - Xiao, Huiqing

AU - Setterquist, Robert

AU - Li, Hailong

AU - Jacobson, Jeffrey

AU - Garcia, Joe G N

AU - Ye, Shui Qing

PY - 2008

Y1 - 2008

N2 - Increasing evidence indicates that the beneficial "pleiotropic" effects of statins on clinical events involve nonlipid mechanisms including the modification of blood vessel endothelial cell function. However, the involved molecular events and pathways are not completely understood. In the present study, Affymetrix microarrays were used to monitor the temporal gene expression of human coronary artery endothelial cells (HCAEC) treated with simvastatin (Sim) to gain insight into statins' direct effects on the endothelial function. We isolated and labeled mRNA from HCAEC treated with Sim for 0, 3, 6, 12, 24, and 48 h and hybridized these samples to Affymetrix GeneChip HG-U95Av2 to analyze the temporal gene expression profile. Out of 12,625 genes present on the HG-U95Av2 GeneChip, expression of 5,432 genes was detected. There were 1,475 of 5,432 genes that displayed the differential expression compared to baseline (0 h). Fifty-four genes were upregulated (≤twofold) while 61 genes were downregulated (≥ twofold) at 24-48 h after the Sim treatment. Many new target genes and pathways modulated by Sim were uncovered. This study indicates that many aspects of the pleiotropic effect of Sim on the endothelial cell function can be mediated by transcriptional control. Physiological function of 22% of 115 differentially expressed genes in Sim-treated HCAEC are currently unknown. These newly identified genes could be useful for new mechanistic study and new therapeutic modalities. Expressions of 13 out of 18 genes (>70%) in the cell cycle/ proliferation control process were significantly inhibited by the Sim treatment. CDC25B and ITGB4 gene expressions were validated by RT-PCR and Western blotting. Sim's inhibitory effect of on HCAEC growth was confirmed by the measurement of [3H]thymidine incorporation into the DNA synthesis. Further in-depth analysis of this effect may shed light on molecular mechanisms of Sim's beneficial inhibition of neointima formation in the atherosclerotic artery stenosis.

AB - Increasing evidence indicates that the beneficial "pleiotropic" effects of statins on clinical events involve nonlipid mechanisms including the modification of blood vessel endothelial cell function. However, the involved molecular events and pathways are not completely understood. In the present study, Affymetrix microarrays were used to monitor the temporal gene expression of human coronary artery endothelial cells (HCAEC) treated with simvastatin (Sim) to gain insight into statins' direct effects on the endothelial function. We isolated and labeled mRNA from HCAEC treated with Sim for 0, 3, 6, 12, 24, and 48 h and hybridized these samples to Affymetrix GeneChip HG-U95Av2 to analyze the temporal gene expression profile. Out of 12,625 genes present on the HG-U95Av2 GeneChip, expression of 5,432 genes was detected. There were 1,475 of 5,432 genes that displayed the differential expression compared to baseline (0 h). Fifty-four genes were upregulated (≤twofold) while 61 genes were downregulated (≥ twofold) at 24-48 h after the Sim treatment. Many new target genes and pathways modulated by Sim were uncovered. This study indicates that many aspects of the pleiotropic effect of Sim on the endothelial cell function can be mediated by transcriptional control. Physiological function of 22% of 115 differentially expressed genes in Sim-treated HCAEC are currently unknown. These newly identified genes could be useful for new mechanistic study and new therapeutic modalities. Expressions of 13 out of 18 genes (>70%) in the cell cycle/ proliferation control process were significantly inhibited by the Sim treatment. CDC25B and ITGB4 gene expressions were validated by RT-PCR and Western blotting. Sim's inhibitory effect of on HCAEC growth was confirmed by the measurement of [3H]thymidine incorporation into the DNA synthesis. Further in-depth analysis of this effect may shed light on molecular mechanisms of Sim's beneficial inhibition of neointima formation in the atherosclerotic artery stenosis.

KW - Coronary artery endothelial cells

KW - Gene expression

KW - Microarray

KW - Simvastatin

UR - http://www.scopus.com/inward/record.url?scp=58149522770&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149522770&partnerID=8YFLogxK

U2 - 10.3727/105221608786883834

DO - 10.3727/105221608786883834

M3 - Article

VL - 14

SP - 229

EP - 239

JO - Gene Expression

JF - Gene Expression

SN - 1052-2166

IS - 4

ER -