Effects Of All-trans Retinoic Acid On Proliferation Of Rat Vascular Smooth Muscle Cells And Expressions Of Cyclin D₁ Protein And Cyclin-Dependent Kinase(CDK) Inhibitor P27 Protein

objective To investigate the effects of all-trans retinoic acid (ATRA ) on proliferation of rat vascular smooth muscle cells ( VSMC) , synthesis of DNA, expressions of Cyclin D\ protein and Cyclin-Dependent Kinase Inhibitor (CKI) P27 protein, and to discuss probable mechanisms of all-trans retinoic acid .Methods Vascular smooth muscle cells from rat aorta were cultured with explant method. Fetal bovine serum and ATRA were added into the serum-free media at the concentrations of 20% and 2.5 mol L-1 respectively. VSMC were harvested after 24h of stimulation. The proliferation of VSMC and the synthesis of DNA were examined with 3H-TdR incorporation. The protein levels of cyclin D] and CKI P27 were examined with western blotting and picture analysation.Results (1) Compared with free control group, FBS increased more 3H-TdR incorporation (P<0.001) and acercelerated proliferation and synthesis of DNA in VSMC in FBS group. 3H-TdR incorporation of ATRA group which was added with ATRA and 20% FBS simultaneously decreased more than that of FBS group (P<0.01). ATRA inhibited significantly proliferation and synthesis of DNA in VSMC. (2) The level of cyclin D1 protein of VSMC in FBS group which were stimulated by 20% FBS was significantly higer than that of free control group (P<0.01). The level of cyclin D1 protein of VSMC in ATRA group was significantly lower than that of VSMC in FBS group (P<0.01). (3) The level of P27 protein of VSMC in FBS group was significantly lower than that of free control group (P<0.01). While in ATRA group, the level of P27 protein was higher than that of FBS group (P<0.01).Conclusions ATRA has increased 3H-TdR incorporation of VSMC, inhibited the proliferation, upregulated the level of cyclin DI protein and downregulated the level of P27 protein. The possible mechanism is associated with the downregulation of cyclin D1 protein and the upregulation of CKI P27 protein.Postgraduate: Han Xiaoning (Medicine.cardiology) Directed by Professor Dong Guoxiong...