title: MicroRNA-145 restores contractile vascular smooth muscle phenotype and coronary collateral growth in the metabolic syndrome.
abstract: OBJECTIVE
  Transient, repetitive occlusion stimulates coronary collateral growth (CCG) in normal animals. Vascular smooth muscle cells (VSMCs) switch to synthetic phenotype early in CCG, then return to contractile phenotype. CCG is impaired in the metabolic syndrome. We determined whether impaired CCG was attributable to aberrant VSMC phenotypic modulation by miR-145-mediated mechanisms, and whether restoration of physiological miR-145 levels in metabolic syndrome (JCR rat) improved CCG.
  
  
  RESULTS
  CCG was stimulated by transient, repetitive left anterior descending artery occlusion and evaluated after 9 days by coronary blood flow measurements (microspheres). miR-145 was delivered to JCR VSMCs via adenoviral vector (miR-145-Adv). In JCR rats, miR-145 was decreased late in CCG (≈ 2-fold day 6; ≈ 4-fold day 9 versus SD), which correlated with decreased expression of smooth muscle-specific contractile proteins (≈ 5-fold day 6; ≈ 10-fold day 9 versus SD), indicative of VSMCs' failure to return to the contractile phenotype late in CCG. miR-145 expression in JCR rats (miR-145-Adv) on days 6 to 9 of CCG completely restored VSMCs contractile phenotype and CCG (collateral/normal zone flow ratio was 0.93 ± 0.09 JCR+miR-145-Adv versus 0.12 ± 0.02 JCR versus 0.87 ± 0.02 SD).
  
  
  CONCLUSIONS
  Restoration of VSMC contractile phenotype through miR-145 delivery is a highly promising intervention for restoration of CCG in the metabolic syndrome.
authors: Department of Biochemistry and Molecular Biology, University of South Alabama College of Medicine, 307 N University Blvd, Mobile, AL 36688, USA.
authors: Rebecca
authors: R
authors: Hutcheson
authors: Russell
authors: R
authors: Terry
authors: Jennifer
authors: J
authors: Chaplin
authors: Erika
authors: E
authors: Smith
authors: Alla
authors: A
authors: Musiyenko
authors: James C
authors: JC
authors: Russell
authors: Thomas
authors: T
authors: Lincoln
authors: Petra
authors: P
authors: Rocic
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D003097:Collateral Circulation; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D035683:MicroRNAs / Q000378:metabolism*; D009124:Muscle Proteins / Q000096:biosynthesis; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D013997:Time Factors; D014661:Vasoconstriction
chemical_list: D035683:MicroRNAs; D009124:Muscle Proteins
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