The effect of oligomeric procyanidins on endothelial function and cholesterol homeostasis

Abstract

Oligomeric procyanidins (OPC) are naturally occurring dietary substances, which studies suggest can protect against cardiovascular disease. To explore this further a double-blind randomised controlled crossover trial, EPICURE (Evaluation of high procyanidin intervention with dark chocolate on underlying age-related elements of cardiovascular risk) examined the effects of high procyanidin dark chocolate (HPDC) versus low procyanidin dark chocolate (LPDC) on various cardiovascular parameters in subjects with early hypertension. This was complemented by in vitro studies of OPC on cultured bovine aortic endothelial cells (BAEC) to determine the effect on cellular cholesterol levels. HPDC reduced 24 h blood pressure (-2/0.6 mmHg) and heart rate (-3.3 bpm), but only the latter reached statistical significance (p < 0.001). Augmentation pressure, augmentation index, plasma lipid levels, apolipoproteins, HDL subclasses, and hsCRP were not different amongst the groups. Retrospective analysis suggests that the study was underpowered and there were only 21 subjects with completed data due to technical issues. Future clinical studies should be designed with sufficient statistical power to detect changes in vascular function. In addition, compliance should be checked, technical errors detected earlier and FMD rather than PWA should be used to measure endothelial vascular function. OPC in vitro increased expression of the oxysterol cholesterol 25-hydroxylase (peaking at 1 h; p < 0.001) which suppressed the mRNA levels of HMGCR as previously reported (at 6 h; p < 0.01). In addition the mRNA for ABCG1 was increased (at 24 h p < 0.01), which has not been described to date in the literature. This implicates that OPC favour overall reduced cellular cholesterol via increased efflux and reduced synthesis. But when BAEC were loaded with LDLC, OPC reduced both cell media and solubilised cell extract cholesterol levels, the former being greater, suggesting no enhancement in cholesterol efflux. Also there was poor reproducibility of the ABCG1 mRNA expression which was likely to be due to variable transcription of the reference gene. Despite this the in vitro results support a potential role for OPC in reducing cellular cholesterol levels and future studies should employ radioactive methods to measure cholesterol efflux.