Casein-Derived Tripeptide, Val-Pro-Pro (VPP), Modulates Monocyte Adhesion to Vascular Endothelium

Aim: A food-derived bioactive tripeptide, Val-Pro-Pro (VPP), has been shown to possess angiotensin I-converting enzyme (ACE) inhibitory activity and foods containing such peptides exhibit an antihypertensive effect in clinical settings. Methods: The present study focused on the effect of VPP on monocyte adhesion to endothelium under flow conditions using phorbol 12-myristate 13-acetate (PMA)-stimulated monocytic THP-1 cells. Results: Pre-incubation of THP-1 cells with VPP (1 mm, 24 hours) significantly decreased the PMA-induced adhesion of THP-1 cells (P<0.05) to human umbilical vein endothelial cells (HUVECs). PMA-induced up-regulation of beta 1 and beta 2 integrin activation in THP-1 cells was downregulated by VPP, which significantly suppressed only the PMA-induced phosphorylation of JNK (p<0.05) in THP-1 cells. In addition, preincubation of THP-1 with SP600125, a specific inhibitor of JNK, resulted in significant reduction of the PMA-induced adhesion of THP-1. Interestingly, another tripeptide with comparable ACE inhibitory activity, Leu-Gly-Pro (LGP), failed to reduce the PMA-induced adhesion of THP-1, suggesting a distinct anti-inflammatory effect of VPP on THP-1 adhesion. Conclusion: These observations suggest that VPP moderates monocyte adhesion to inflamed endothelia via attenuation of the JNK pathway in monocytes, which might contribute to the primary prevention of atherosclerosis.