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

Abstract

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 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.

Folic Acid and Vitamin B12 Administration in CKD, Why Not?

“…We have previously reported that supplementation with 5-MTHF versus folic acid improved survival rate without differences in homocysteine levels [ 11 ]. Pan et al recently showed that folic acid treatment can inhibit atherosclerosis progression through the reduction of VSMC dedifferentiation in high-fat-fed LDL receptor-deficient mice [ 64 ].…”

Hydrogen sulfide lowers hyperhomocysteinemia dependent on cystathionine γ lyase S‐sulfhydration in ApoE‐knockout atherosclerotic mice

“…High levels of homocysteine can induce oxidative stress, inflammation, ER stress, and epigenetic changes, cause endothelial dysfunction (Lai & Kan, ) and vascular smooth muscle cell dysplasia (Luo et al, ), and accelerate thrombosis (Dionisio, Jardin, Salido, & Rosado, ) and foam cell formation (Chernyavskiy, Veeranki, Sen, & Tyagi, ), thus promoting atherogenesis. Although some studies have shown that folic acid supplementation reduced atherosclerotic plaque size in ApoE‐knockout mice (Cui et al, ) or LDL receptor‐knockout mice (Pan et al, ), it did not reduce early atherosclerosis with HHcy in humans (Cacciapuoti, ). H 2 S donors per se can decrease atherosclerosis.…”

Rapamycin Suppresses Penile NADPH Oxidase Activity to Preserve Erectile Function in Mice Fed a Western Diet

“…The mTORC1/p70S6K axis may serve as a nexus that connects overnutrition to accelerated cardiovascular aging and cardiovascular disease pathogenesis [ 30 , 31 ]. Indeed, overnutrition with a high-fat diet has been shown to increase active site phosphorylation of mTOR and p70S6K in the heart and aorta, while in vivo treatment with rapamycin blocks this pathway [ 32 , 33 , 34 ]. The present study demonstrates that chronic consumption of a Western style high-fat/high-sucrose diet induces elevated active site phosphorylation of mTOR and p70S6K in the corpus cavernosum, both of which were suppressed by rapamycin treatment.…”