Open AccessFolic acid delays development of atherosclerosis in low‐density lipoprotein receptor‐deficient mice
Author(s) -
Pan Sunlei,
Liu Huahua,
Gao Feidan,
Luo Hangqi,
Lin Hui,
Meng Liping,
Jiang Chengjian,
Guo Yan,
Chi Jufang,
Guo Hangyuan
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13599
Subject(s) - oil red o , oxidative stress , ldl receptor , endocrinology , medicine , osteopontin , vascular smooth muscle , western blot , pi3k/akt/mtor pathway , chemistry , lipoprotein , biology , signal transduction , biochemistry , cholesterol , adipose tissue , smooth muscle , gene , adipogenesis
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 ( VSMC s) 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 findings suggest that FA attenuates atherosclerosis development and inhibits VSMC dedifferentiation in high‐fat‐fed LDLR −/− mice by reduced lipid levels and inhibiting oxidative stress and the inflammatory response through mTOR /p70S6K signalling pathway.