Established atherosclerosis might be a prerequisite for chicory and its constituent protocatechuic acid to promote endothelium-dependent vasodilation in mice

Scope Chicory (Cichorium intybus L. var. foliosum, Belgian endive), a typical Mediterranean vegetable, and its constituent protocatechuic acid (PCA) can inhibit established atherosclerosis progression. We thus investigated whether chicory can improve vascular relaxation, a critical pathway for combating atherosclerosis, and whether PCA is a contributor to a chicory‐induced effect. Methods and results Apolipoprotein E‐deficient (ApoE−/−) mice with established atherosclerosis and C57BL/6J mice without atherosclerosis were fed an AIN‐93G diet, or AIN‐93G plus 0.5% freeze‐dried chicory or 0.003% PCA for 1 wk. In ApoE−/− mice, both chicory and PCA consumption increased endothelium‐dependent vasodilation and endothelial nitric oxide synthase (eNOS) activity independent of eNOS and phospho‐eNOS Ser1177 and Thr495 protein expression. Chicory‐ or PCA‐induced eNOS activities were associated with increased vascular tetrahydrobiopterin (BH4) levels that result from reduced BH4 oxidation partially through preventing eNOS uncoupling. In C57BL/6J mice, neither chicory nor PCA consumption affected endothelium‐dependent vasodilation and eNOS activity. Notably, in vitro studies showed that PCA increases eNOS activity in mouse aortic endothelial cells in co‐culture with macrophage foam cells, but not in aortic endothelial cells alone. Conclusions Chicory improves eNOS‐mediated endothelium‐dependent vasodilation by increasing BH4 levels in mice with established atherosclerosis, which might be partially ascribed to its constituent PCA. Chicory, a typical Mediterranean vegetable, and its constituent protocatechuic acid (PCA) are able to inhibit atherosclerosis development. It is found that chicory and PCA promote endothelial nitric oxide synthase (eNOS)‐mediated vasodilation in apolipoprotein E‐deficient mice with established atherosclerosis but not in its wide‐type C57BL/6J mice free of atherosclerosis. In vitro studies further show that PCA increases eNOS activity in mouse aortic endothelial cells in co‐culture with macrophage foam cells, but not in aortic endothelial cells alone.