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 mult iple 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 mus cle cells (SMCs) in primary culture, but not in the quiescent SMCs of intact human aorta, High levels of PDE1C were found in primary culture s of SMCs derived from explants of human newborn and adult aortas, and in SMCs cultured from severe atherosclerotic lesions. PDE1C was the m ajor cAMP hydrolytic activity in these SMCs. PDE expression patterns i n 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 detec table calmodulin-stimulated PDE. These findings suggest that many of t he commonly used animal species may not provide good models for studyi ng the roles of PDEs in proliferation of human SMCs. More importantly, the observation that PDE1C is induced only in proliferating SMCs sugg ests that it may be both an indicator of proliferation and a possible target for treatment of atherosclerosis or restenosis after angioplast y, conditions in which proliferation of arterial SMCs is negatively mo dulated by cyclic nucleotides.