Milk-derived bioactive peptides and their health promoting effects: a potential role in atherosclerosis

Abstract

Bioactive peptides derived from milk proteins are food components that, in addition to their nutritional value, retain many biological properties and have therapeutic effects in several health disorders, including cardiovascular disease. Amongst these, atherosclerosis is the underlying cause of heart attack and strokes. It is a progressive dyslipidaemic and inflammatory disease where accumulation of oxidized lipids and inflammatory cells leads to the formation of an atherosclerotic plaque in the vessel wall. Milk-derived bioactive peptides can be released during gastrointestinal digestion, food processing or by enzymatic and bacterial fermentation and are considered to promote diverse beneficial effects such as lipid lowering, antihypertensive, immnomodulating, anti-inflammatory and antithrombotic effects. In this review, an overview of the diverse biological effects of these compounds is given, particularly focusing on their beneficial properties on cardiovascular disease and proposing novel mechanisms of action responsible for their bioactivity. Attempts to prevent cardiovascular diseases target modifications of several risk factors such as high blood pressure, obesity, high blood concentrations of lipids or insulin resistance. Milk-derived bioactive peptides are a source of health-enhancing components and the potential health benefit of these compounds has a growing commercial potential. Consequently, they have been incorporated as ingredients in functional foods, as dietary supplements and as pharmaceuticals to promote health and reduce risk of chronic diseases.

Keywords: atherosclerosis; bioactive peptides; cardiovascular disease; immunomodulation; inflammation; milk proteins.

Figure 1

Schematic illustrating generation of milk‐derived bioactive peptides and their physiological functionalities. Milk‐derived bioactive peptides can be encrypted in both casein (α‐, β‐, γ‐ and κ‐casein) and whey proteins (β‐lactoglobulin, α‐lactalbumin, serum albumin, immunoglobulins, lactoferrin, protease‐peptone fractions). Generation of peptides may be induced in several ways, by enzymatic hydrolysis or microbial fermentation, in vivo during digestion by digestive enzymes, like trypsin, and by gut microbial enzymes, during food processing, by ripening or by in vitro hydrolysis using isolated enzymes. Numerous health promoting effects have been attributed to milk derived bioactive peptides released from dairy proteins by enzymatic proteolysis, including antithrombotic, antihypertensive, anti‐inflammatory, anti‐oxidative, antimicrobial and anti‐obesity

Figure 2

The role of the endothelial cell and monocyte in early stages of atherosclerosis: potential mechanisms of milk derived bioactive peptides. Activated ECs express selectins (P‐selectin and E‐selectin) and cell adhesion molecules (VCAM‐1 and ICAM‐1), which mediate the rolling and firm adhesion of the monocyte along the vessel wall. Firmly adhered monocytes undergo transendothelial monocyte migration from the lumen to the intima in response to chemokines such as MCP‐1. Upon entering the underlying intima the monocyte is exposed to the growth factor MCS‐F, which differentiates the monocyte into a macrophage. Macrophage differentiation results in the up‐regulation of the scavenger receptors, CD36 and SRA1, which are necessary for the subsequent formation of foam cells following the uptake of ox‐LDL and other modified lipids. Bioactive peptides have anti‐inflammatory effects on ECs by inhibiting activation of the NF‐κB pathway in a PPARγ dependent manner, and by modifying the expression of CCR2 and TLR4 receptors in monocytes