Spirulina platensis, a
water blue-green alga, has been associated with potent
biological effects, which might have important relevance in atheroprotection. We investigated whether S. platensis or
phycocyanobilin (PCB), its tetrapyrrolic chromophore, can activate atheroprotective
heme oxygenase-1 (Hmox1), a key
enzyme in the
heme catabolic pathway responsible for generation of a potent
antioxidant bilirubin, in endothelial cells and in a mouse model of
atherosclerosis. In vitro experiments were performed on EA.hy926 endothelial cells exposed to extracts of S. platensis or PCB. In vivo studies were performed on
ApoE-deficient mice fed a
cholesterol diet and S. platensis. The effect of these treatments on Hmox1, as well as other markers of oxidative stress and endothelial dysfunction, was then investigated. Both S. platensis and PCB markedly upregulated Hmox1 in vitro, and a substantial overexpression of Hmox1 was found in aortic atherosclerotic lesions of
ApoE-deficient mice fed S. platensis. In addition, S. platensis treatment led to a significant increase in Hmox1 promoter activity in the spleens of Hmox-luc transgenic mice. Furthermore, both S. platensis and PCB were able to modulate important markers of oxidative stress and endothelial dysfunction, such as eNOS, p22
NADPH oxidase subunit, and/or
VCAM-1. Both S. platensis and PCB activate atheroprotective HMOX1 in endothelial cells and S. platensis increased the expression of Hmox1 in aortic atherosclerotic lesions in
ApoE-deficient mice, and also in Hmox-luc transgenic mice beyond the
lipid lowering effect. Therefore, activation of HMOX1 and the
heme catabolic pathway may represent an important mechanism of this food supplement for the reduction of atherosclerotic disease.