- Background and aims Polysaccharides (PSs) produced by the red microalga Porphyridium sp. were reported to exhibit anti-inflammatory bioactivities in the human skin. The primary goal of the present research was to assess whether PSs attenuate inflammatory processes by interfering with tumour necrosis factor-alpha (TNF-α)-induced inflammation, in human coronary artery endothelial cells (HCAECs). Methods Functional and inflammatory markers were quantified in TNF-α-stimulated HCAECs, with and without pre-treatment with PSs. The expression/activation of these markers was assessed by Western immunoblotting and a luciferase reporter assay. NO levels were measured using the Griess method and intracellular reactive oxygen stress (ROS) was determined with the fluorescent probe 2′,7'-dichlorodihydro-fluorescein diacetate (H2DCFDA). Results The TNF-α-induced up-regulation of the inter-cellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) translocation, as well as IκB degradation were significantly attenuated in cells pre-treated with PSs. In addition, PSs were able to inhibit NF-κB activation as well as TNF-α-induced oxidative stress in HCAECs. Endothelial function was also improved, as measured by increased nitric oxide (NO) formation and decreased endothelin (ET-1) protein expression. Conclusions This is the first report that demonstrates the anti-inflammatory effect and vaso-relaxing property of red microalgae PSs in a HCAEC- TNF-α induced system. This study lays the foundations for basic research concerning the PS mode of action in biochemical processes involving endothelial dysfunction, and it also holds potential for applied research, possibly promoting the use of PSs as a therapeutic agent or food additive to improve vascular health.