Cardioprotective Peptides from Dry-Cured Ham in Primary Endothelial Cells and Human Plasma: An Omics Approach

Cardiovascular diseases are a leading cause of mortality, driving the search for alternative preventive strategies. This study investigates the antioxidant effects, among others, of a mixture of four bioactive peptides (BPs) derived from dry-cured pork ham on endothelial cells from healthy (C-HUVECs) and gestational diabetes (GD-HUVECs) pregnancies, as well as human plasma, using an integrative omics approach. Human umbilical vein endothelial cells (HUVECs) were treated with 300 μM purified BP, followed by transcriptomic and proteomic analyses. The results revealed significant alterations in mitochondrial gene expression and downregulation of genes associated with inflammation and oxidative stress in healthy HUVECs. Furthermore, BP treatment modulated key signalling pathways, including Ras and MAPK, leading to changes in the phosphorylation of ERK, AKT, and NF-κB, suggesting potential cardioprotective effects. The effects of BP were compared to those of the antioxidant hydroxytyrosol, highlighting their relative efficacy in vascular protection. The proteomic analysis of human plasma demonstrated BP-induced modulation of lipid metabolism, inflammation, and oxidative stress with notable changes in proteins such as APOA1 and MMP-8. These natural compounds demonstrate significant preventive potential in vascular health, highlighting their promise as effective tools for reducing cardiovascular risk before the progression of the pathology. These findings emphasize the importance of integrative omics in understanding the mechanisms behind BP's effects and suggest promising applications for nutraceuticals aimed at cardiovascular protection.