Whey protein hydrolysate induced modulation of endothelial cell gene expression

Whey protein concentrate (WPC) hydrolysates generated using Neutrase (R), Alcalase (R) and Flavourzyme (R) 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 mu g/rnL). Incubation of human umbilical vein endothelial cells with 5 kDa permeates of Neutrase (R)- and Alcalase (R)-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 (R)- and Neutrase (R)-hydrolysates, respectively. Peptide sequences within the 5 kDa permeate of the Alcalase (R)-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.