Abstract
Atherosclerotic cardiovascular disease has a high mortality worldwide. Our lab previously purified a polysaccharide designated as CM1 with (1→4)-β-D-Glcp and (1→2)-α-D-Manp glycosyls as the backbone. In this study, we investigated the anti-atherosclerosis effect of CM1 and the underlying mechanisms of action in a low-density lipoprotein receptor knockout (LDLR(-/-) mouse model. It was found that CM1 significantly decreased the formation of atherosclerotic plaques. Mechanistically, CM1 enhanced plasma level of apolipoprotein A-I and decreased the plasma levels of triglyceride, apolipoprotein B, and total cholesterol. In the absence of LDLR, CM1 elevated the expression of very low-density lipoprotein receptor for liver uptake of plasma apolipoprotein B-containing particles and reduced hepatic triglyceride synthesis by inhibiting sterol regulatory element binding protein 1c. CM1 improved lipids excretion by increasing the liver X receptor α/ATP-binding cassette G5 pathway in small intestine. CM1 reduced lipogenesis and lipolysis by inhibiting peroxisome proliferator-activated receptor γ and adipose triglyceride lipase in epididymal fat. Furthermore, CM1 improved lipid profile in C57BL/6J mice. Collectively, CM1 can modulate lipid metabolism by multiple pathways, contributing to reduced plasma lipid level and formation of atherosclerotic plaques in LDLR(−/−) mice. This molecule could be explored as a potential compound for prevention and treatment of hyperlipidemia and atherosclerosis.
Highlights
Cardiovascular disease (CVD) is the leading cause of death in modern society, in some developing countries (Torres et al, 2015; Zhao et al, 2019)
Rabbit polyclonal antibody against ATP-binding cassette (ABC) G5, mouse monoclonal antibodies against PPARα and γ, Niemann-Pick C1-like protein 1 (NPC1L1), adipose triglyceride lipase (ATGL), SREBP1c and 2, lipoprotein lipase (LPL), and very low-density lipoprotein (VLDL) receptor (VLDLR) were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, United States)
Oil Red O staining results confirmed the successful establishment of the atherosclerosis model in low-density lipoprotein receptor (LDLR)(-/-) mice fed with the high-fat chow
Summary
Cardiovascular disease (CVD) is the leading cause of death in modern society, in some developing countries (Torres et al, 2015; Zhao et al, 2019). Hyperlipidemia is a lifestyle risk factor for atherosclerotic CVD and becomes a major cause of CVD in developing countries due to lack of preventive measures (Zhao et al, 2019). CVD is not be completely eliminated by the current therapeutic strategies (Guo et al, 2020; Lin et al, 2021a). For this reason, researchers are prompted to search for new therapies for the prevention and treatment of CVD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
