Fucoidan for cardiovascular application and the factors mediating its activities

Abstract

Fucoidan is a sulfated polysaccharide with various bioactivities. The application of fucoidan in cancer treatment, wound healing, and food industry has been extensively studied. However, the therapeutic value of fucoidan in cardiovascular diseases has been less explored. Increasing number of investigations in the past years have demonstrated the effects of fucoidan on cardiovascular system. In this review, we will focus on the bioactivities related to cardiovascular applications, for example, the modulation functions of fucoidan on coagulation system, inflammation, and vascular cells. Factors mediating those activities will be discussed in detail. Current therapeutic strategies and future opportunities and challenges will be provided to inspire and guide further research.

Keywords: Biological function; Cardiovascular disease; Structure; Sulfated fucan; Therapeutic strategy.

Figure 1.

Fucoidan structure with mono-(1–3)-α-_L-fucopyranose backbone and repeated (1–3)- and (1–4)-α-_L-fucopyranose backbone

Figure 2.

Coagulation pathways and the role of fucoidan. Fucoidan exhibits anticoagulant activity by inhibiting FXa formation in the intrinsic pathway (Drozd et al., 2006; Lapikova et al., 2008; Nishino et al., 1999). Fucoidan improves the activity of heparin cofactor II and antithrombin III in inactivating thrombin by binding to antithrombin III and heparin cofactor II (Colliec et al., 1991; Mansour et al., 2019; Minix & Doctor, 1997). Fucoidan inhibits fibrinogen-thrombin reaction by binding to the thrombin attacking site in fibrinogen (Nishino, Aizu, & Nagumo, 1991; Nishino, Ura, & Nagumo, 1995). Fucoidan also promotes fibrinolytic effect by simulating t-PA catalyzed plasminogen activation (Ghebouli et al., 2018; Soeda, Sakaguchi, Shimeno, & Nagamatsu, 1992). The figure was created with BioRender.com.

Figure 3.

Three complement activation pathways and the role of fucoidan in complement activation. Fucoidan inhibits complement activation through the classical pathway by preventing active C1 formation, inhibiting C4 activity by forming a complex with C4, and preventing the binding of C4b and C2a (Blondin et al., 1994; Tissot, Montdargent, et al., 2003). Fucoidan also inhibits complement activation through the alternative pathway by preventing the binding of factor B to C3b (Blondin et al., 1994). The figure was created with BioRender.com.

Figure 4.

The use of fucoidan as functional molecules for polyvinyl alcohol (PVA) small diameter vascular grafts. (A) Modification of PVA by fucoidan. (B) Fucoidan (PVA-F) significantly improved endothelial cell adhesion on PVA. (C) Fucoidan modified PVA vascular grafts (PVA-Fg) yielded a lower re-stenosis percentage. Reproduced with permission from Ref (Yao et al., 2020).

Figure 5.

(A) Structures of monosaccharides. (B) Structures of fucoidan, reproduced with permission from Ref (Oliveira et al., 2020).

Figure 6.

The use of fucoidan as a targeted drug delivery system and imaging agent. (A) Nanoparticles functionalized with fucoidan showed targeted delivery of recombinant tissue plasminogen activator (rt-PA) to the thrombus site. Reproduced with permission from Ref (Juenet et al., 2018). (B) Ultrasmall particles of iron oxide (USPIOs) functionalized with fucoidan localized inside the aneurysm wall, presenting a significant contrast enhancement on magnetic resonance imaging (MRI) of abdominal aortic aneurysm (AAA). Adapted with permission from Ref (Bonnard, Serfaty, et al., 2014).