Abstract
Danlou tablet (DLT), a commercial Chinese patent medicine, has been widely used to treat cardiovascular diseases for many years. Atherosclerosis (AS) is the leading cause of cardiovascular disease. Increasing evidence indicates that autophagy plays a vital role in the development of AS. Here we investigated whether DLT could activate autophagy to improve AS and further clarified its underlying mechanisms. In an ApoE−/− mice model, the results of Oil red O, Masson’s trichrome, and H&E staining techniques showed that DLT significantly inhibited lipid accumulation and fibrosis formation in atherosclerotic plaque tissue. DLT also inhibited serum triglyceride, cholesterol, and low-density lipoprotein levels and suppressed serum levels of inflammatory factors interleukin-6 and tumor necrosis factor-α in ApoE−/− mice. Moreover, DLT suppressed proliferation, migration, and invasion of human vascular adventitial fibroblasts (HVAFs) by inhibiting the PI3K/Akt/mTOR pathway. In addition, western blot analysis showed that Danlou tablet treatment decreased the expression of p62 and increased Beclin 1 and LC3 I -to-LC3 II ratios in HVAFs. The role of autophagy in treating atherosclerosis by DLT is confirmed by 3-methyladenine (autophagy inhibitor) and rapamycin (autophagy activator) in HVAFs. In summary, DLT activated PI3K/Akt/mTOR-mediated autophagy of vascular adventitial fibroblasts to protect cells from damage caused by atherosclerosis.
Highlights
Atherosclerosis (AS), characterized by the accumulation of lipids and inflammatory cells in arterial walls, is a common pathological basis for many cardiovascular diseases (CVDs) (Falk, 2006)
Abnormal lipid metabolism usually occurs in the initial stages of AS (Schaftenaar et al, 2016), especially concerning oxidized lowdensity lipoproteins (Ox-low-density lipoprotein (LDL)), leading to the accumulation of foam cells and the formation of lipid plaques on blood vessel walls; this leads to luminal stenosis and alterations in the structure of blood vessel walls (Ference, 2018; Pirillo et al, 2018)
In order to investigate the biochemical basis that leads to the pathological results, we collected serum samples from the mice to determine the blood total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels and inflammatory factors, like IL-6 and TNF-α
Summary
Atherosclerosis (AS), characterized by the accumulation of lipids and inflammatory cells in arterial walls, is a common pathological basis for many cardiovascular diseases (CVDs) (Falk, 2006). Abnormal lipid metabolism usually occurs in the initial stages of AS (Schaftenaar et al, 2016), especially concerning oxidized lowdensity lipoproteins (Ox-LDL), leading to the accumulation of foam cells and the formation of lipid plaques on blood vessel walls; this leads to luminal stenosis and alterations in the structure of blood vessel walls (Ference, 2018; Pirillo et al, 2018). Inflammatory factors IL-6 and TNF-α play an essential role in all the stages of atherosclerosis, including plaque formation, progression, and rupture. It has been clinically verified that mTOR inhibitors, such as rapamycin, can efficiently inhibit the growth of atherosclerotic plaques (Martinet et al, 2014; Zhai et al, 2014)
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