Folic acid delays development of atherosclerosis in low‐density lipoprotein receptor‐deficient mice

作者：Sunlei Pan, Huahua Liu, Feidan Gao, Hangqi Luo, Hui Lin, Liping Meng, Chengjian Jiang, Yan Guo, Jufang Chi, Hangyuan Guo · 发表于：Journal of Cellular and Molecular Medicine · 年份：2018 · DOI：10.1111/jcmm.13599 · 被引用次数：24 · 研究领域：Adipokines, Inflammation, and Metabolic Diseases、Nuclear Receptors and Signaling、Lipoproteins and Cardiovascular Health

Many studies support the cardioprotective effects of folic acid (FA). We aimed to evaluate the utility of FA supplementation in preventing the development of atherosclerotic in low-density lipoprotein receptor-deficient (LDLR-/-) mice and to elucidate the molecular processes underlying this effect. LDLR-/- mice were randomly distributed into four groups: control group, HF group, HF + FA group and the HF + RAPA group. vascular smooth muscle cells (VSMCs) were divided into the following four groups: control group, PDGF group, PDGF + FA group and PDGF + FA + RAPA group. Blood lipid levels, oxidative stress and inflammatory cytokines were measured. Atherosclerosis severity was evaluated with oil red O staining. Haematoxylin and eosin (H&E) staining was used to assess atherosclerosis progression. Immunohistochemical staining was performed with antismooth muscle α-actin (α-SMA) antibodies and anti-osteopontin (OPN) antibodies that demonstrate VSMC dedifferentiation. The protein expression of α-SMA, OPN and mechanistic target of rapamycin (mTOR)/p70S6K signalling was detected by Western blot analysis. FA and rapamycin reduced serum levels of total cholesterol, triacylglycerol, LDL, inhibiting oxidative stress and the inflammatory response. Oil red O and H&E staining demonstrated that FA and rapamycin inhibited atherosclerosis. FA and rapamycin treatment inhibited VSMC dedifferentiation in vitro and in vivo, and FA and rapamycin attenuated the mTOR/p70S6K signalling pathway. Our find...