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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:1225.)
© 2000 American Heart Association, Inc.

Vascular Biology

Intracellular Ca²⁺ Handling in Vascular Smooth Muscle Cells Is Affected by Proliferation

Olivier Vallot; Laurent Combettes; Philippe Jourdon; Jocelyn Inamo; Isabelle Marty; Michel Claret; Anne-Marie Lompré

From CNRS EP 1088 (O.V., P.J., J.I., A.-M.L.) and INSERM U 442 (L.C., M.C.), IFR-FR 46 Signalisation cellulaire, Université Paris-sud, Orsay, France, and DBMS/BMC (I.M.), CEA, Grenoble, France.

Correspondence to Dr A.-M. Lompré, Biochime, Faculté de Pharmacie, IFR-75, Université Paris-sud, F 92296-Chatenay-Malabry, France. E-mail anne-marie.lompre{at}egm.u-psud.fr

Abstract—Despite intensive interest in the dedifferentiation process of vascular smooth muscle cells, very little data are available on intracellular Ca²⁺ signaling. The present study was designed to investigate the evolution of the intracellular Ca²⁺ pools when rat aortic smooth muscle cells (RASMCs) proliferate and to define the mechanisms involved in the functional alterations. RASMCs were cultured in different conditions, and [Ca²⁺]_i was measured by use of fura 2. Expression of the sarco(endo)plasmic reticulum Ca²⁺ pumps (SERCA2a and SERCA2b), Ca²⁺ channels, the ryanodine receptor (RyR), and the inositol trisphosphate receptor (IP3R) was studied by reverse transcription–polymerase chain reaction and immunofluorescence. Antibodies specific for myosin heavy chain isoforms were used as indicators of the differentiation state of the cell, whereas an anti–proliferating cell nuclear antigen antibody was a marker of proliferation. SERCA2a, SERCA2b, RyR3, and IP3R-1 mainly were present in the aorta in situ and in freshly isolated RASMCs. These cells used the 2 types of Ca²⁺ channels to release Ca²⁺ from a common thapsigargin-sensitive store. Proliferation of RASMCs, induced by serum or by platelet-derived growth factor-BB, resulted in the disappearance of RyR and SERCA2a mRNAs and proteins and in the loss of the caffeine- and ryanodine-sensitive pool. The differentiated nonproliferative phenotype was maintained in low serum or in cells cultured at high density. In these conditions, RyR and SERCA2a were also present in RASMCs. Thus, expression of RyR and SERCA2a is repressed by cell proliferation, inducing loss of the corresponding Ca²⁺ pool. In arterial smooth muscle, Ca²⁺ release through RyRs is involved in vasodilation, and suppression of the ryanodine-sensitive pool might thus alter the control of vascular tone.

Key Words: vascular smooth muscle • cell proliferation • Ca²⁺ pumps • ryanodine receptors • inositol trisphosphate receptors

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