The underlying mechanism of 16-Hydroxy-cleroda-3,13-dien-15,16-olide on high glucose with FFA induction of VSMC migration and proliferation

• Main Authors: Min-Han Shih, 施旻含
• Other Authors: Ching-Feng Weng
• Format: Others
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/77511918355016031905

碩士 === 國立東華大學 === 生命科學系 === 101 === Epidemiological studies have indicated that atherosclerosis is the underlying major cause of clinical cardiovascular disease (CVD) events. In diabetic patients might increase the risk of atherosclerosis. When people suffered from both CVD and T2DM have higher incidence of death than others causes. However, the interplay mechanism of atherosclerosis, diabetes, and hyperlipidemia is poorly understood. The inhibition of vascular smooth muscle cell (VSMC) migration and proliferation is an important stage to prevent the progression of atherosclerosis. In the present study, VSMCs were isolated from the wild type (WT) and Caveolin-1 knockout (Cav-1 KO) mice, the cultured VSMCs were employed to investigate the proliferation and migration in FFAs (Oleic acid, OA; Palmitic acid, PA; Lysophosphatidylcholine, LPC, and OA plus LPC) in low (LG) and high glucose (HG) conditions. The results showed that the FFA-induced in HG condition could increase VSMC proliferation, especially the OA plus LPC could induce higher proliferation ability in Cav-1 KO VSMCs than those of WT VSMCs, which were through the increase of PCNA, cyclin D1, and PI3K/AKT expression. And the FAK expression could regulate VSMC both proliferation and migration. Additionally, glucose- and FFA-induced could increase VSMC migration, especially in HG condition with FFA could induce higher migration ability and also increased extracellular matrix (ECM) degradation by the activated MMP-2 expression. The data showed that glucose- and FFA-induced were increased cdc42, Rac1, ERK1/2, and c-Src expression to induce VSMC migration. The 16-Hydroxy-cleroda-3,13-dien-15,16-olide (HCD), a clerodane diterpenoid compound, was isolated from the Polyalthia longifolia. In the second experiment we examined whether HCD could inhibit VSMCs proliferation and migration in glucose- and FFA-induced. The results showed that HCD had effectively to restrain VSMC proliferation and migration ability via the decrease of MMP-2 activity. HCD may become an alternative medicine for preventing the proliferation and migration ability of VSMCs in the future.