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

Abstract

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.

Keywords: Atherosclerosis; Chicory; Endothelial function; Macrophage; Protocatechuic acid.