Asst professor University of Nebraska-Lincoln Lincoln, Nebraska, United States
Abstract: Vascular inflammation, endothelial dysfunction, and plaque formation in the blood vessels are the significant symptoms of the development of atherosclerosis and associated cardiovascular diseases (CVDs) affecting nearly 37% population in the United States. Dietary γ-glutamyl valine (γ-EV), naturally found in dry beans, has exhibited beneficial biological activities to reduce chronic inflammation. The intervention of γ-EV was found to reduce the tumor necrosis factor-ɑ (TNF-ɑ)-induced inflammatory responses in vascular endothelial cells via the activation of vascular calcium-sensing receptor (CaSR). TNF-ɑ treatment significantly increased the expression of inflammatory adhesion molecules (VCAM-1, E-Selectin), chemokine (MCP-1), and cytokines (IL-6 and IL-8). However, γ-EV (1 mM) intervention significantly downregulated the expression of these biomarkers. γ-EV was found to transport across the intestinal monolayer via the PepT1 transporter and paracellular pathways, with the apparent permeability (Papp) of 1.56×10–6 cm/s. The efficacy of γ-EV was further evaluated in vivo, through Apolipoprotein E (Apo-E)-deficient (Apo E-/-) mice, an animal model genetically sensitive to the development of atherosclerosis. High-fat diet (HFD: 40 kcal% fat, 1.25% cholesterol) fed ApoE-/- mice significantly increased the expression of inflammatory biomarkers such as VCAM-1, ICAM-1, LOX-1, and MCP-1. However, γ-EV (150 mg/kg BW) treatment significantly decreased the expression of these biomarkers and improved the pathological characteristics of the atherosclerotic plaques in the aorta. In addition, the FoxP3+ and CD25+ splenic T-reg cells were significantly decreased in the γ-EV-treated group. Thus, the present study highlights the potential use of γ-glutamyl peptides, as a functional food ingredient for the prevention and management of CVDs.