Cardiovascular disease (CVD), caused by endothelial dysfunction and subendothelial monocyte accumulation due to an imbalance in lipid metabolism, has led to an increasing number of deaths worldwide from CVD over the past decade, according to reports. CVD is already the leading cause of human death worldwide. Monocyte-derived macrophages are unable to effectively alleviate the inflammatory response, ultimately leading to the formation of atherosclerotic plaques.
Currently, statins are recommended as the first choice for patients with high adiposity who are at high risk for CVD. However, there are side effects of statins, including myalgia, myositis, and rhabdomyolytic liver damage, which may increase the risk of hemorrhagic stroke in patients with cerebrovascular disease.
On the other hand, fucoidan has been found to have various physiological activities such as lipid-lowering, anti-atherosclerosis, and anticoagulation without any side effects.
So, in this blog, I would like to inform of you the study, “Application of fucoidan as a treatment for cardiovascular and cerebrovascular diseases” by Ke Wang et al.
Reverse cholesterol transport (RCT) plays an important role in atherosclerosis (AS). The RCT is a study on the physiological process of transporting peripheral lipids to the liver via high-density lipoproteins (HDL) in the blood, where the liver breaks down and converts cholesterol, and then excretes the lipids in the small intestine. It has become a major target for therapy. RCTs have also been found to be potential targets for fucoidan.
The study showed that Fucoidan extracted from Kjellmaniella crassifolia can complete the outflow of intracellular free cholesterol by up-regulating scavenger receptor class B type I (SR-B1), LDL receptor (LDLR), ATP-binding cassette transporter ABCG1, and ABCA1 expression in a hyperlipidemic rat model ApoE mice and phagocytizing and clearing the excess peripheral lipids via their transport to the liver by HDL that is the first step in RCT. Peroxisome proliferator-activated receptors (PPARs) α and β are also important nodal proteins in cholesterol regulation. Fucoidan increases the amount of PPARα and promotes the metabolism and excretion of cholesterol in the liver, and ABCA1 and ABCG8 break down and metabolize cholesterol transported to the liver. Levels of cholesterol 7-hydroxylase (CYP7A1), which breaks down cholesterol into bile salts or bile acids, are also increased. Cholesterol can also be reabsorbed and transported by Niemann-Pick C1-like 1 apolipoprotein located in the brush border membrane of enterocytes. It is converted into ABCG5/G8 membrane proteins and ultimately excreted in vitro. Fucoidan can affect the expression of genes and proteins related to the process of RCT, reduce lipid levels, and slow the progression of AS.
At the site of atherosclerotic plaque rupture, exposure to highly thrombotic matrix proteins and procoagulant factors triggers platelet recruitment. Platelet activation plays an important role in maintaining thrombus stability and preventing platelet activation, thereby preventing aggregation and interfering with the growth of the developing thrombus. Highly sulfated fucoidan with a molecular weight of 3900 Da has specific inhibitory activity against platelet aggregation and low anticoagulant activity and is considered to be a more suitable antithrombotic agent, with a lower risk of bleeding in vivo.
As atherosclerosis continues to progress, macrophages also become activated and promote the migration and proliferation of vascular smooth muscle cells. Collagen fibers are synthesized and secreted, gradually covering the surface of the lesion area and forming the cap structure of the fibrous plaque. Under the continued activity of an inflammatory environment, IFNγ secreted by T cells reduces the ability of vascular smooth muscle to synthesize collagen, while matrix metalloproteinases (MMPs) released by macrophages degrade collagen and disrupt the cap structure. weakens and destabilizes. Therefore, various secondary lesions such as blood clots and plaque rupture can easily occur, ultimately leading to severe cardiovascular disease. Therefore, treatment of macrophages may perform autophagy, a cell and tissue self-renewal process, and degrade lipids within foam cells, which is particularly important in foam cell formation. Fucoidan enhances the autophagy-lysosome system of foam cells and increases cellular autophagy to degrade lipids, thus playing a role in anti-atherosclerotic defense. Fusion of autophagosomes and lysosomes allows the removal of improperly folded or polymerized proteins, excess or damaged cells, and intracellular pathogens.
Fucoidan reduces the expression of endothelin-1, proinflammatory cytokines interferon (IFN)-γ, and tumor necrosis factor-α (TNF)-α, reduces the intensity of inflammation, improves metabolic disorders, and improves endothelial It can protect cells from damage. Furthermore, fucoidan increases immune activation, reduces the release of inflammatory cytokines, and reduces damage to endothelial cells. It also reduces lipid accumulation in foam cells by enhancing autophagy.
The above research will further explore the application prospects of fucoidan in cardiocerebrovascular diseases and provide some rationale and inspiration for full-scale development and utilization.
Source: Ther Adv Chronic Dis. 2022; 13: 20406223221076891. doi:10.1177/20406223221076891