Atherosclerotic plaque destabilization and
rupture leads to
acute coronary syndromes which cause serious damage to human health worldwide. However, there is currently a lack of efficient therapeutic methods.
Mammalian target of rapamycin (mTOR) has been suggested to be involved in the development of
atherosclerotic plaques and serves as a therapeutic target. The present study was performed to determine whether RNA interference (RNAi) of mTOR in vivo by LV‑mediated
small hairpin RNA (
shRNA) was capable of inhibiting the progression of
atherosclerotic plaques. LV‑mediated
shRNA against mTOR (LV‑shmTOR) was designed and obtained. Male
apolipoprotein E‑deficient mice were fed a high‑fat diet and a constrictive collar was placed around the right carotid arteries of these mice to induce plaque formation. Eight weeks after surgery, mice were randomly divided into the mTOR RNA interference (LV‑shmTOR) group, receiving treatment with LV‑mTOR‑shRNA; the LV‑shCON group, receiving treatment with LV‑non‑specific‑shRNA; and the control group, receiving treatment with phosphate‑buffered saline. Following transfection, the mice were sacrificed to evaluate the effects of mTOR expression silencing on
atherosclerosis. Transfection of LV‑mTOR‑shRNA markedly inhibited the
mRNA and
protein expression levels. Knockdown of mTOR ameliorated dysregulated blood lipid metabolism and stabilized aortic
atherosclerotic plaques by decreasing the plaque area and increasing the fibrous cap and cap‑to‑core ratio. Furthermore, macrophages were decreased by silencing mTOR in
atherosclerotic plaques. In addition, western blot analysis revealed that the knockdown of mTOR increased autophagy‑related
protein 13 (Atg13) dephosphorylation and light chain 3‑I/light chain 3‑II (LC3‑I/LC3‑II) ratios, both of which were associated with a high activity of autophagy, suggesting an increase of autophagy in
atherosclerotic plaques. Moreover, genes including
matrix metalloproteinase 2,
monocyte chemoattractant protein 1 and
tissue factor, which promote plaque instability, were downregulated by silencing mTOR. These results demonstrate that LV‑mediated mTOR silencing by RNAi treatment induces macrophage autophagy and is a potential strategy for the treatment of
atherosclerotic plaques.