Article Text

GW24-e2996 Involvement of retinol binding protein 4 in insulin-induced vascular smooth muscle cell proliferation
  1. Li Fei,
  2. Tianlun Yang
  1. Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410078, China


Objectives Retinol binding protein 4 (RBP4)- a newly discovered adipocytokines, has been found to be associated with obesity, insulin resistance, cardiac vascular disease (CVD), metabolic syndrome closely. Recent researchs have suggested RBP4 may play an important role in the occurrence and development of AS and CVD. Abnormal proliferation and migration of vascular smooth muscle cell (VSMC) is one of the common foundation of atherosclerosis, vascular restenosis and other CVD, which is related to a variety of signal transduction pathways, such as Mitogen-activated protein kinase (MAPK) pathway, JAK/STAT pathway. This study used high concentrations of insulin to stimulate rat aortic smooth muscle cell (RASMCs) to observe proliferation of RVSMC, and used RBP4 as intervention factor in RASMCs at the first time, to clear causal relationship between RBP4 and proliferation of VSMC, to further clarify the influence RBP4 on VSMC’s proliferation and its mechanism.

Methods The insulin-induced proliferation of RASMCs which were obtained from ATCC (Manassas, Virginia) was analysed by using the MTT and cell cycle assays. The expression of extracellular signal-regulated kinase (ERK)1/2, Phospho-ERK1/2(P-ERK1/2), janus kinase (JAK)2, Phospho-JAK2(P-JAK2), Signal transducer and activator of transcription (STAT)3, Phospho-STAT3(P- STAT3) in RASMCs were assessed by western blotting. RBP4, specific JAK1/2 inhibitor PD98059 and JAK2 inhibitor AG490 were used as intervention factors.

Results Insulin induced proliferation of RASMCs in a concentration- and time-dependent manner, while most effectively in 10-5 M and 24hours. Insulin enhanced the expression of ERK1/2, P-ERK1/2, JAK2, P-JAK2, STAT3, P-STAT3 in a time-dependent manner as shown by the results of western blotting. RBP4 enhanced insulin-induced proliferation of RASMCs and expression of P-ERK1/2 and P-JAK2. Blockade of ERK1/2 signalling pathway inhibited RBP4-induced proliferation of RASMCs.

Conclusions These results suggest that RBP4 mediates the proliferation of VSMCs induced by insulin via activation of MAPK signaling pathway, which set the stage for a prominent role of RBP4 as a modulator of the atherosclerosis in hyperinsulinemia in understanding many unexpected aspects of the cardiovascular diseases.

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