Effects of cyclic stretch on the molecular regulation of myocardin in rat aortic vascular smooth muscle cells

Chiung Zuan Chiu, Bao Wei Wang, Kou Gi Shyu

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Abstract. Background: The expression of myocardin, a cardiac-restricted gene, increases during environmental stress. How mechanical stretch affects the regulation of myocardin in vascular smooth muscle cells (VSMCs) is not fully understood. We identify the mechanisms and pathways through which mechanical stretch induces myocardin expression in VSMCs. Results. Rat VSMCs grown on a flexible membrane base were stretched to 20% of maximum elongation, at 60 cycles per min. An in vivo model of aorta-caval shunt in adult rats was also used to investigate myocardin expression. Cyclic stretch significantly increased myocardin and angiotensin II (AngII) expression after 18 and 6 h of stretch. Addition of extracellular signal-regulated kinases (ERK) pathway inhibitor (PD98059), ERK small interfering RNA (siRNA), and AngII receptor blocker (ARB; losartan) before stretch inhibited the expression of myocardin protein. Gel shift assay showed that myocardin-DNA binding activity increased after stretch. PD98059, ERK siRNA and ARB abolished the binding activity induced by stretch. Stretch increased while myocardin-mutant plasmid, PD98059, and ARB abolished the promoter activity. Protein synthesis by measuring [§ssup§3§ esup§H]proline incorporation into the cells increased after cyclic stretch, which represented hypertrophic change of VSMCs. An in vivo model of aorta-caval shunt also demonstrated increased myocardin protein expression in the aorta. Confocal microscopy showed increased VSMC size 24 h after cyclic stretch and VSMC hypertrophy after creation of aorta-caval shunt for 3 days. Conclusions: Cyclic stretch enhanced myocardin expression mediated by AngII through the ERK pathway in cultured rat VSMCs. These findings suggest that myocardin plays a role in stretch-induced VSMC hypertrophy.

Original languageEnglish
Article number50
JournalJournal of Biomedical Science
Volume20
Issue number1
DOIs
Publication statusPublished - 2013

Fingerprint

Vascular Smooth Muscle
Smooth Muscle Myocytes
Muscle
Rats
Cells
Extracellular Signal-Regulated MAP Kinases
Venae Cavae
Aorta
Angiotensin II
Hypertrophy
Small Interfering RNA
myocardin
Proteins
Losartan
Confocal microscopy
Angiotensin Receptor Antagonists
Cell Size
Proline
Confocal Microscopy
Elongation

Keywords

  • ERK pathway
  • Myocardin
  • Stretch
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Pharmacology (medical)
  • Medicine(all)

Cite this

Effects of cyclic stretch on the molecular regulation of myocardin in rat aortic vascular smooth muscle cells. / Chiu, Chiung Zuan; Wang, Bao Wei; Shyu, Kou Gi.

In: Journal of Biomedical Science, Vol. 20, No. 1, 50, 2013.

Research output: Contribution to journalArticle

@article{dcbf5ba251e444b4ba0e17a25b000ce5,
title = "Effects of cyclic stretch on the molecular regulation of myocardin in rat aortic vascular smooth muscle cells",
abstract = "Abstract. Background: The expression of myocardin, a cardiac-restricted gene, increases during environmental stress. How mechanical stretch affects the regulation of myocardin in vascular smooth muscle cells (VSMCs) is not fully understood. We identify the mechanisms and pathways through which mechanical stretch induces myocardin expression in VSMCs. Results. Rat VSMCs grown on a flexible membrane base were stretched to 20{\%} of maximum elongation, at 60 cycles per min. An in vivo model of aorta-caval shunt in adult rats was also used to investigate myocardin expression. Cyclic stretch significantly increased myocardin and angiotensin II (AngII) expression after 18 and 6 h of stretch. Addition of extracellular signal-regulated kinases (ERK) pathway inhibitor (PD98059), ERK small interfering RNA (siRNA), and AngII receptor blocker (ARB; losartan) before stretch inhibited the expression of myocardin protein. Gel shift assay showed that myocardin-DNA binding activity increased after stretch. PD98059, ERK siRNA and ARB abolished the binding activity induced by stretch. Stretch increased while myocardin-mutant plasmid, PD98059, and ARB abolished the promoter activity. Protein synthesis by measuring [§ssup§3§ esup§H]proline incorporation into the cells increased after cyclic stretch, which represented hypertrophic change of VSMCs. An in vivo model of aorta-caval shunt also demonstrated increased myocardin protein expression in the aorta. Confocal microscopy showed increased VSMC size 24 h after cyclic stretch and VSMC hypertrophy after creation of aorta-caval shunt for 3 days. Conclusions: Cyclic stretch enhanced myocardin expression mediated by AngII through the ERK pathway in cultured rat VSMCs. These findings suggest that myocardin plays a role in stretch-induced VSMC hypertrophy.",
keywords = "ERK pathway, Myocardin, Stretch, Vascular smooth muscle cells",
author = "Chiu, {Chiung Zuan} and Wang, {Bao Wei} and Shyu, {Kou Gi}",
year = "2013",
doi = "10.1186/1423-0127-20-50",
language = "English",
volume = "20",
journal = "Journal of Biomedical Science",
issn = "1021-7770",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Effects of cyclic stretch on the molecular regulation of myocardin in rat aortic vascular smooth muscle cells

AU - Chiu, Chiung Zuan

AU - Wang, Bao Wei

AU - Shyu, Kou Gi

PY - 2013

Y1 - 2013

N2 - Abstract. Background: The expression of myocardin, a cardiac-restricted gene, increases during environmental stress. How mechanical stretch affects the regulation of myocardin in vascular smooth muscle cells (VSMCs) is not fully understood. We identify the mechanisms and pathways through which mechanical stretch induces myocardin expression in VSMCs. Results. Rat VSMCs grown on a flexible membrane base were stretched to 20% of maximum elongation, at 60 cycles per min. An in vivo model of aorta-caval shunt in adult rats was also used to investigate myocardin expression. Cyclic stretch significantly increased myocardin and angiotensin II (AngII) expression after 18 and 6 h of stretch. Addition of extracellular signal-regulated kinases (ERK) pathway inhibitor (PD98059), ERK small interfering RNA (siRNA), and AngII receptor blocker (ARB; losartan) before stretch inhibited the expression of myocardin protein. Gel shift assay showed that myocardin-DNA binding activity increased after stretch. PD98059, ERK siRNA and ARB abolished the binding activity induced by stretch. Stretch increased while myocardin-mutant plasmid, PD98059, and ARB abolished the promoter activity. Protein synthesis by measuring [§ssup§3§ esup§H]proline incorporation into the cells increased after cyclic stretch, which represented hypertrophic change of VSMCs. An in vivo model of aorta-caval shunt also demonstrated increased myocardin protein expression in the aorta. Confocal microscopy showed increased VSMC size 24 h after cyclic stretch and VSMC hypertrophy after creation of aorta-caval shunt for 3 days. Conclusions: Cyclic stretch enhanced myocardin expression mediated by AngII through the ERK pathway in cultured rat VSMCs. These findings suggest that myocardin plays a role in stretch-induced VSMC hypertrophy.

AB - Abstract. Background: The expression of myocardin, a cardiac-restricted gene, increases during environmental stress. How mechanical stretch affects the regulation of myocardin in vascular smooth muscle cells (VSMCs) is not fully understood. We identify the mechanisms and pathways through which mechanical stretch induces myocardin expression in VSMCs. Results. Rat VSMCs grown on a flexible membrane base were stretched to 20% of maximum elongation, at 60 cycles per min. An in vivo model of aorta-caval shunt in adult rats was also used to investigate myocardin expression. Cyclic stretch significantly increased myocardin and angiotensin II (AngII) expression after 18 and 6 h of stretch. Addition of extracellular signal-regulated kinases (ERK) pathway inhibitor (PD98059), ERK small interfering RNA (siRNA), and AngII receptor blocker (ARB; losartan) before stretch inhibited the expression of myocardin protein. Gel shift assay showed that myocardin-DNA binding activity increased after stretch. PD98059, ERK siRNA and ARB abolished the binding activity induced by stretch. Stretch increased while myocardin-mutant plasmid, PD98059, and ARB abolished the promoter activity. Protein synthesis by measuring [§ssup§3§ esup§H]proline incorporation into the cells increased after cyclic stretch, which represented hypertrophic change of VSMCs. An in vivo model of aorta-caval shunt also demonstrated increased myocardin protein expression in the aorta. Confocal microscopy showed increased VSMC size 24 h after cyclic stretch and VSMC hypertrophy after creation of aorta-caval shunt for 3 days. Conclusions: Cyclic stretch enhanced myocardin expression mediated by AngII through the ERK pathway in cultured rat VSMCs. These findings suggest that myocardin plays a role in stretch-induced VSMC hypertrophy.

KW - ERK pathway

KW - Myocardin

KW - Stretch

KW - Vascular smooth muscle cells

UR - http://www.scopus.com/inward/record.url?scp=84880119385&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880119385&partnerID=8YFLogxK

U2 - 10.1186/1423-0127-20-50

DO - 10.1186/1423-0127-20-50

M3 - Article

C2 - 23855625

AN - SCOPUS:84880119385

VL - 20

JO - Journal of Biomedical Science

JF - Journal of Biomedical Science

SN - 1021-7770

IS - 1

M1 - 50

ER -