title: Regulatory effect of thromboxane A2 on proliferation of vascular smooth muscle cells from rats.
abstract: We investigated the regulatory effects of the vasoconstrictor thromboxane A2 on the proliferation of vascular smooth muscle cells (VSMC) from Wistar-Kyoto rats using 9,11-epithio-11,12-methano-thromboxane A2 (STA2), a stable analogue of thromboxane A2. STA2 dose dependently increased incorporation of [3H]thymidine into DNA in randomly cycling VSMC and significantly shortened the doubling time. Cell cycle analysis revealed that the increased cell cycle progression was primarily due to a rapid transition from the DNA synthetic (S) to the G2/mitotic (M) phase. Moreover, STA2 enhanced protein synthesis in VSMC during the G2/M phase, whereas the protein synthesis was unaffected in the G0/G1 period. In fact, STA2 prompted the cells in G2/M phase to synthesize actin, a major cytoskeleton protein. Conversely, inhibition of protein synthesis by puromycin retarded the transition from S to G2/M. In addition, depolymerization of the actin molecules by cytochalasin D offset the quick progression to the G2/M phase by STA2. These data indicate that thromboxane A2 stimulates the cell cycle progression in VSMC primarily through a rapid transition from S to G2/M. This enhanced progression is attributable partly to a rapid buildup of the cytoskeleton proteins during the G2/M period.
authors.affiliation: Second Department of Medicine, University of Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nagata
authors.forename: Y
authors.initials: Y
authors.lastname: Uehara
authors.forename: A
authors.initials: A
authors.lastname: Numabe
authors.forename: T
authors.initials: T
authors.lastname: Ishimitsu
authors.forename: N
authors.initials: N
authors.lastname: Hirawa
authors.forename: T
authors.initials: T
authors.lastname: Ikeda
authors.forename: H
authors.initials: H
authors.lastname: Matsuoka
authors.forename: T
authors.initials: T
authors.lastname: Sugimoto
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*
chemical_list: D003598:Cytoskeletal Proteins; D013928:Thromboxane A2; C037866:STA 2