Calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1C) is induced in human arterial smooth muscle cells of the synthetic, proliferative phenotype.
The diversity among cyclic nucleotide phosphodiesterases provides multiple mechanisms for regulation of cAMP and cGMP in the cardiovascular system. Here we report that a calmodulin-stimulated phosphodiesterase (PDE1C) is highly expressed in proliferating human arterial smooth muscle cells (SMCs) in primary culture, but not in the quiescent SMCs of intact human aorta. High levels of PDE1C were found in primary cultures of SMCs derived from explants of human newborn and adult aortas, and in SMCs cultured from severe atherosclerotic lesions. PDE1C was the major cAMP hydrolytic activity in these SMCs. PDE expression patterns in primary SMC cultures from monkey and rat aortas were different from those from human cells. In monkey, high expression of PDE1B was found, whereas PDE1C was not detected. In rat SMCs, PDE1A was the only detectable calmodulin-stimulated PDE. These findings suggest that many of the commonly used animal species may not provide good models for studying the roles of PDEs in proliferation of human SMCs. More importantly, the observation that PDE1C is induced only in proliferating SMCs suggests that it may be both an indicator of proliferation and a possible target for treatment of atherosclerosis or restenosis after angioplasty, conditions in which proliferation of arterial SMCs is negatively modulated by cyclic nucleotides.
Rybalkin
S D
SD
Department of Pharmacology, University of Washington, Seattle 98195, USA.
Bornfeldt
K E
KE
Sonnenburg
W K
WK
Rybalkina
I G
IG
Kwak
K S
KS
Hanson
K
K
Krebs
E G
EG
Beavo
J A
JA
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000096:biosynthesis*; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000096:biosynthesis*; D000328:Adult; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000201:enzymology* / Q000473:pathology; D001161:Arteriosclerosis / Q000201:enzymology* / Q000473:pathology; D002478:Cells, Cultured; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D004790:Enzyme Induction; D000882:Haplorhini; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology* / Q000473:pathology; D010641:Phenotype; D010727:Phosphoric Diester Hydrolases; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D013398:Sudden Infant Death; D014158:Transcription, Genetic
D011994:Recombinant Proteins; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; C517265:PDE1A protein, human; C517266:PDE1B protein, human; C517272:PDE1C protein, human; C517274:Pde1C protein, rat; C517263:Pde1a protein, rat; C517269:Pde1b protein, rat; D015106:3',5'-Cyclic-GMP Phosphodiesterases