8 Citations (Scopus)

Abstract

Mechanical stretch leads to cardiac hypertrophy and may ultimately cause heart failure. However, the effect of mechanical stretch on gene induction in cardiomyocytes remains to be determined. In the present study, we compared transcript profiles of mechanically stretched neonatal rat cardiomyocytes with those of unstretched cells using cDNA microarrays. The microarrays contained probes for 480 known genes, including those involved in signal transduction, cell cycle regulation, the cytoskeleton and cell motility. Eighteen genes, including the eNOS gene, were identified as having significantly differential expression in response to mechanical stretch in cardiomyocytes. Northern and western blot analysis further quantified the expression of the eNOS gene. Mechanical stretch increased constitutive NOS activity and nitric oxide (NO) production. The NO donor s-nitroso-N-acetylpenicillamine (SNAP) inhibited mechanical stretch-stimulated protein synthesis, as measured by [ 3H]-leucine uptake. In addition, cardiomyocytes were infected with adenoviral vectors encoding cDNA for eNOS (Ad-eNOS) and a phosphoglycerate kinase (PGK) empty vector (Ad-PGK). In contrast with Ad-PGK-infected cells, in cardiomyocytes infected with Ad-eNOS, there was increased calcium-dependent NOS activity and nitrite production. Cardiomyocytes infected with Ad-eNOS exhibited diminished mechanical stretch-stimulated protein synthesis. In contrast, in eNOS-knockdown cells, the increased eNOS protein levels and NOS activity induced by mechanical stretch were abolished, but protein synthesis was enhanced. The results of the present study indicate that eNOS gene expression is induced by mechanical stretch, leading to increased constitutive NOS activity and NO production, which may be a negative regulator in cardiomyocyte hypertrophy.

Original languageEnglish
Pages (from-to)559-566
Number of pages8
JournalClinical and Experimental Pharmacology and Physiology
Volume36
Issue number5-6
DOIs
Publication statusPublished - May 2009

Fingerprint

Nitric Oxide Synthase Type III
Cardiac Myocytes
Gene Expression
Phosphoglycerate Kinase
Genes
Nitric Oxide
Proteins
Nitric Oxide Donors
Cardiomegaly
Nitrites
Oligonucleotide Array Sequence Analysis
Cytoskeleton
Leucine
Northern Blotting
Hypertrophy
Cell Movement
Signal Transduction
Cell Cycle
Heart Failure
Complementary DNA

Keywords

  • Cardiomyocytes
  • cDNA microarray
  • Endothelial nitric oxide synthase
  • Mechanical stretch

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Pharmacology

Cite this

Mechanical stretch induces endothelial nitric oxide synthase gene expression in neonatal rat cardiomyocytes. / Cheng, Tzu-Hurng; Chen, Jeremy J W; Shih, Neng Lang; Lin, Jia Wei; Liu, Ju Chi; Chen, Yen Ling; Chen, Cheng Hsien; Chen, Jin Jer.

In: Clinical and Experimental Pharmacology and Physiology, Vol. 36, No. 5-6, 05.2009, p. 559-566.

Research output: Contribution to journalArticle

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abstract = "Mechanical stretch leads to cardiac hypertrophy and may ultimately cause heart failure. However, the effect of mechanical stretch on gene induction in cardiomyocytes remains to be determined. In the present study, we compared transcript profiles of mechanically stretched neonatal rat cardiomyocytes with those of unstretched cells using cDNA microarrays. The microarrays contained probes for 480 known genes, including those involved in signal transduction, cell cycle regulation, the cytoskeleton and cell motility. Eighteen genes, including the eNOS gene, were identified as having significantly differential expression in response to mechanical stretch in cardiomyocytes. Northern and western blot analysis further quantified the expression of the eNOS gene. Mechanical stretch increased constitutive NOS activity and nitric oxide (NO) production. The NO donor s-nitroso-N-acetylpenicillamine (SNAP) inhibited mechanical stretch-stimulated protein synthesis, as measured by [ 3H]-leucine uptake. In addition, cardiomyocytes were infected with adenoviral vectors encoding cDNA for eNOS (Ad-eNOS) and a phosphoglycerate kinase (PGK) empty vector (Ad-PGK). In contrast with Ad-PGK-infected cells, in cardiomyocytes infected with Ad-eNOS, there was increased calcium-dependent NOS activity and nitrite production. Cardiomyocytes infected with Ad-eNOS exhibited diminished mechanical stretch-stimulated protein synthesis. In contrast, in eNOS-knockdown cells, the increased eNOS protein levels and NOS activity induced by mechanical stretch were abolished, but protein synthesis was enhanced. The results of the present study indicate that eNOS gene expression is induced by mechanical stretch, leading to increased constitutive NOS activity and NO production, which may be a negative regulator in cardiomyocyte hypertrophy.",
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AU - Chen, Jeremy J W

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AU - Chen, Yen Ling

AU - Chen, Cheng Hsien

AU - Chen, Jin Jer

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N2 - Mechanical stretch leads to cardiac hypertrophy and may ultimately cause heart failure. However, the effect of mechanical stretch on gene induction in cardiomyocytes remains to be determined. In the present study, we compared transcript profiles of mechanically stretched neonatal rat cardiomyocytes with those of unstretched cells using cDNA microarrays. The microarrays contained probes for 480 known genes, including those involved in signal transduction, cell cycle regulation, the cytoskeleton and cell motility. Eighteen genes, including the eNOS gene, were identified as having significantly differential expression in response to mechanical stretch in cardiomyocytes. Northern and western blot analysis further quantified the expression of the eNOS gene. Mechanical stretch increased constitutive NOS activity and nitric oxide (NO) production. The NO donor s-nitroso-N-acetylpenicillamine (SNAP) inhibited mechanical stretch-stimulated protein synthesis, as measured by [ 3H]-leucine uptake. In addition, cardiomyocytes were infected with adenoviral vectors encoding cDNA for eNOS (Ad-eNOS) and a phosphoglycerate kinase (PGK) empty vector (Ad-PGK). In contrast with Ad-PGK-infected cells, in cardiomyocytes infected with Ad-eNOS, there was increased calcium-dependent NOS activity and nitrite production. Cardiomyocytes infected with Ad-eNOS exhibited diminished mechanical stretch-stimulated protein synthesis. In contrast, in eNOS-knockdown cells, the increased eNOS protein levels and NOS activity induced by mechanical stretch were abolished, but protein synthesis was enhanced. The results of the present study indicate that eNOS gene expression is induced by mechanical stretch, leading to increased constitutive NOS activity and NO production, which may be a negative regulator in cardiomyocyte hypertrophy.

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