Regulation of Vascular Endothelial Function by Procyanidin-Rich Foods and Beverages

Abstract

Flavonoid-rich diets are associated with a lower mortality from cardiovascular disease. This has been linked to improvements in endothelial function. However, the specific flavonoids, or biologically active metabolites, conferring these beneficial effects have yet to be fully defined. In this experimental study of the effect of flavonoids on endothelial function cultured endothelial cells have been used as a bioassay with endothelin-1 (ET-1) synthesis being measured an index of the response. Evaluation of the relative effects of extracts of cranberry juice compared to apple, cocoa, red wine, and green tea showed inhibition of ET-1 synthesis was dependent primarily on their oligomeric procyanidin content. Procyanidin-rich extracts of cranberry juice triggered morphological changes in endothelial cells with reorganization of the actin cytoskeleton and increased immunostaining for phosphotyrosine residues. These actions were independent of antioxidant activity. Comparison of the effects of apple procyanidin monomers through heptamer showed a clear structure-activity relationship. Although monomer, dimer, and trimer had little effect on ET-1 synthesis, procyanidin tetramer, pentamer, hexamer, and heptamer produced concentration-dependent decreases with IC(50) values of 5.4, 1.6, 0.9, and 0.7 microM, respectively. Levels of ET-1 mRNA showed a similar pattern of decreases, which were inversely correlated with increased expression of Kruppel-like factor 2 (KLF2), a key endothelial transcription factor with a broad range of antiatherosclerotic actions including suppression of ET-1 synthesis. Future investigations of procyanidin-rich products should assess the role KLF2 induction plays in the beneficial vascular effects of high flavonoid consumption.

Regulation of vascular endothelial genes by dietary flavonoids: structure-expression relationship studies and the role of the transcription factor KLF-2

“…These results correlate with previous studies in which flavonoids as hesperetin [46] or quercetin decreased ET-1 mRNA levels in HUVECs [25]. Although inhibition of ET-1 expression has been associated with an increment of KLF-2 expression [47], our results fail to show enough evidence to state a relationship between KLF-2 and ET-1. In fact, the most active compounds that inhibit ET-1 expression did not produce higher levels of KLF-2 mRNA.…”

Chronic consumption of a low calorie, high polyphenol cranberry beverage attenuates inflammation and improves glucoregulation and HDL cholesterol in healthy overweight humans: a randomized controlled trial

“…Dohadwala et al [19] reported an improvement in vasodilation 2-4 h after a single dose of cranberry juice in an uncontrolled pilot trial, but not following daily consumption (480 mL/day) for 4 week in patients with CAD. Canton et al [52] and Yung et al [53] suggested that procyanidin-rich foods and beverages might decrease ET-1 and increase NO via modulation of their syntheses. However, Mathison et al [14] reported that a single dose of cranberry beverage had no effect on plasma NO in healthy adults and Flammer et al [20] found no change in endothelial function after consumption of a double-strength cranberry juice (460 mL/day) for 4 months in patients with CVD risk factors and endothelial dysfunction.…”

Nutritional advantages of oats and opportunities for its processing as value added foods - a review

“…Traditionally, polyphenols are considered potent antioxidants. Emerging studies shows that polyphenols may have far more important effects in vivo such as enhancing endothelial function (Caton et al 2010), cellular signalling and anti-inflammatory property (Ramos 2008). Oat hulls have not much uses in food but they contain significant amount of soluble ferulic acid; an avenanthramide antioxidant and also several other phenolic acids.…”