Vasoprotection by dietary supplements and exercise: role of TNFα signaling

Abstract

Vascular dysfunction contributes to the pathogenesis of various cardiovascular diseases. Dietary supplements, including fish oil, dietary fibers, and various natural products, and exercise training exert vasoprotective effects. However, the mechanisms underlying the vasoprotective benefits of dietary supplements and physical activity demand extensive investigation. Accumulating evidence suggests that inflammatory cytokine tumor necrosis factor-alpha (TNFα) plays a pivotal role in the dysregulation of macrovascular and microvascular function. TNFα induces vascular inflammation, monocyte adhesion to endothelial cells, vascular oxidative stress, apoptosis, and atherogenic response and participates in the regulation of thrombosis and coagulation through multiple signaling pathways involving NFκB, Sp1, activator protein 1, JNK, p38, STAT3, and so forth. Dietary supplements and exercise training decrease TNFα production and ameliorate TNFα-mediated pathological changes in vasculature. Thus, the inhibitory effects of dietary supplements and physical exercise on TNFα production and TNFα signaling may contribute to their vasoprotective properties.

Figure 1

Dietary supplements (fish oil, dietary fiber, and various flavonoid and nonflavonoid natural products) exert vasoprotective benefits by inhibiting TNFα production and its downstream signaling pathways. There are dichotomies in the effects of exercise training on TNFα production. Whereas acute exercise has been reported to increase the production of proinflammatory cytokines, chronic exercise reduces TNFα levels.

Figure 2

Multiple mechanisms are involved in the vasoprotective effects of dietary supplements and exercise by inhibiting TNFα signaling.