Whey protein hydrolysate induced modulation of endothelial cell gene expression

Whey protein concentrate (WPC) hydrolysates generated using Neutrase®, Alcalase® and Flavourzyme® and their associated ultrafiltration fractions inhibited angiotensin-1-converting enzyme activity (71.14 ± 1.05, 73.22 ± 0.99 and 51.52 ± 5.80% inhibition when assayed at 14.3 µg/mL). Incubation of human umbilical vein endothelial cells with 5 kDa permeates of Neutrase®- and Alcalase®-hydrolysed WPC for 48 h resulted in the beneficial differential expression of genes relevant to blood pressure control, as measured by microarray. Furthermore, real-time reverse transcriptase polymerase chain reaction demonstrated an upregulation of endothelial nitric oxide synthase (+2.14 ± 0.45 and 2.36 ± 0.27-fold) and down-regulation of endothelin-1 (−0.58 ± 0.09 and −0.82 ± 0.11-fold) following incubation with the 5 kDa permeates of Alcalase®- and Neutrase®-hydrolysates, respectively. Peptide sequences within the 5 kDa permeate of the Alcalase®-hydrolysed WPC were identified, many of which have previously been demonstrated as having ACE-inhibitory and/or other bioactivities. These WPC hydrolysates potentially represent sources of bioactive peptides for the beneficial regulation of endothelial cell function.