title: Effects of cyclic stretch on the molecular regulation of myocardin in rat aortic vascular smooth muscle cells.
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 [3H]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.
authors.forename: Chiung-Zuan
authors.initials: CZ
authors.lastname: Chiu
authors.forename: Bao-Wei
authors.initials: BW
authors.lastname: Wang
authors.forename: Kou-Gi
authors.initials: KG
authors.lastname: Shyu
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005419:Flavonoids / Q000008:administration & dosage; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019808:Losartan / Q000008:administration & dosage; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013314:Stress, Mechanical; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D000099251:Myocardin
chemical_list: D000804:Angiotensin II; D048049:Extracellular Signal-Regulated MAP Kinases; D005419:Flavonoids; D019808:Losartan; D009687:Nuclear Proteins; D015534:Trans-Activators; D000099251:Myocardin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one