title: Triiodothyronine Potentiates Vasorelaxation via PKG/VASP Signaling in Vascular Smooth Muscle Cells.
abstract: OBJECTIVE
  Vascular relaxation caused by Triiodothyronine (T3) involves direct activation of endothelial cells (EC) and vascular smooth muscle cells (VSMC). Activation of protein kinase G (PKG) has risen as a novel contributor to the vasorelaxation mechanism triggered by numerous stimuli. We hypothesize that T3-induced vasorelaxation involves PKG/vasodilator-stimulated phosphoprotein (VASP) signaling pathway in VSMC.
  
  
  METHODS
  Human aortic endothelial cells (HAEC) and VSMC were treated with T3 for short (2 to 60 minutes) and long term (24 hours). Nitric oxide (NO) production was measured using DAF-FM. Expression of protein targets was determined using western blot. For functional studies, rat aortas were isolated and treated with T3 for 20 minutes and mounted in a wire myograph. Relaxation was measured by a concentration-dependent response to acetylcholine (ACh) and sodium nitroprusside (SNP).
  
  
  RESULTS
  Aortas stimulated with T3 exhibited augmented sensitivity to ACh and SNP-induced relaxation, endothelium-dependent and endothelium-independent responses, respectively. T3 directly increased vasorelaxation, which was abolished in the presence of a PKG inhibitor. T3 markedly induced phosphorylation of Akt, eNOS and consequently increased NO production in EC. Likewise, T3 induced phosphorylation of VASP at serine 239 via the PKG pathway in VSMC.
  
  
  CONCLUSIONS
  Our findings have uncovered a PKG/VASP signaling pathway in VSMC as a key molecular mechanism underlying T3-induced vascular relaxation.
authors.affiliation: Department of Life Sciences, New York Institute of Technology, Old Westbury, New York, New York, USA.
authors.forename: Sherin
authors.initials: S
authors.lastname: Samuel
authors.affiliation: Department of Internal Medicine, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Kuo
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yi-Da
authors.initials: YD
authors.lastname: Tang
authors.affiliation: Department of Biomedical Sciences, New York Institute of Technology - College of Osteopathic Medicine, Old Westbury, New York, New York, USA.
authors.forename: A Martin
authors.initials: AM
authors.lastname: Gerdes
authors.affiliation: Department of Biomedical Sciences, New York Institute of Technology - College of Osteopathic Medicine, Old Westbury, New York, New York, USA.
authors.forename: Maria Alicia
authors.initials: MA
authors.lastname: Carrillo-Sepulveda
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D014284:Triiodothyronine / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein; D014284:Triiodothyronine; D017869:Cyclic GMP-Dependent Protein Kinases
keywords: Endothelial cell; Non-genomic effect; PKG; Triiodothyronine (T3); Vascular smooth muscle cell; Vasorelaxation; p-VASP