Reduced phosphodiesterase 3 activity and phosphodiesterase 3A level in synthetic vascular smooth muscle cells: implications for use of phosphodiesterase 3 inhibitors in cardiovascular tissues.
Vascular smooth muscle cells (VSMC) in situ function to control contraction and are said to express a contractile phenotype. However, during development or in response to vascular damage, VSMC proliferate and express a more synthetic phenotype. A survey of literature values for contractile and synthetic VSMC phosphodiesterase (PDE) 3 and PDE4 activities identified a marked difference in the PDE3 and PDE4 activities of these cells. In this study, a comparison of PDE3 and PDE4 activities in contractile and synthetic VSMC demonstrates that a reduced PDE3/PDE4 activity ratio in synthetic VSMC correlates with a reduced PDE3 activity and is associated with marked reductions in PDE3A mRNA and protein levels. Because we show that similar reductions in PDE3 activity and PDE3A levels occur upon culture of human aortic VSMC and that this phenomenon associates with the phenotypic switch that occurs to VSMC in response to vascular damage, our findings are presented in the context that PDE3 inhibition might be expected to selectively alter functions of contractile VSMC.
Dunkerley
Heather A
HA
Department of Pharmacology and Toxicology, Queen's University at Kingston, Kingston, Ontario, Canada.
Tilley
Douglas G
DG
Palmer
Daniel
D
Liu
Hanguan
H
Jimmo
Sandra L
SL
Maurice
Donald H
DH
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D016503:Drug Delivery Systems; D015870:Gene Expression; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction
D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; C517287:PDE3A protein, human; C517290:Pde3a protein, rat; D006152:Cyclic GMP