Vasodilating dipeptide Trp-His can prevent atherosclerosis in apo E-deficient mice

Abstract

Most of the investigations for an alternative medicinal treatment on atherosclerosis have been focused on natural or dietary compounds including phytochemicals. So far, few studies regarding anti-atherosclerotic small peptides except for tetrapeptide of Lys-Arg-Glu-Ser have been reported. The present study was, thus, to investigate whether dipeptide Trp-His, which is one of vasodilating small peptides, could reduce atherosclerotic lesions in apo E-deficient mice fed a high-fat diet. The animal study involved a 9-week-successive administration of Trp-His at a dose of 0, 10 or 100 mg/kg per d. After 9-week administration, en face analyses provided the first direct evidence that the atherosclerotic lesion area was significantly reduced by 27 and 38 % for Trp-His dosed at 10 and 100 mg/kg per d, respectively, compared with the control group. Administration of Trp-His did not affect growth parameters such as body weight and feeding efficiency (P>0·1). Total serum cholesterol and HDL-cholesterol as well as lipid profiles in the liver did not differ between the tested groups. Taken together, the anti-atherosclerotic effect of dipeptide Trp-His should be addressed into physiological functions of bioactive peptides, in which the dipeptide may elicit the power by alternative mechanism(s), not by the regulation of lipid metabolism.

Diet and Atherosclerosis in Apolipoprotein E-Deficient Mice

“…We investigated whether the dipeptide Try-His, a vasodilating small peptide, can reduce atherosclerotic lesions in apoEÀ/À mice fed a high-fat diet. 107) The study involved a 9 weeks of successive administration of Try-His at doses of 0, 10, or 100 mg/kg per day. En face analyses provided direct evidence that the atherosclerotic lesion area was significantly reduced, by 27 and 38%, for Try-His dosed at 10 and 100 mg/kg per day respectively, as compared with the control group.…”

Effect of the Uncharged Imidazolium Moiety in Adenine on Endothelium-Independent Relaxation in the Contracted Thoracic Aorta of Sprague-Dawley Rats

“…It has also been demonstrated that Trp-His could ameliorate the atherosclerotic vascular dysfunction in apolipoprotein E-deficient mice. 4) However, 1-or 3-methyl-His-Arg-Trp and His-Arg-Ala diminished the power of their mother peptide, His-Arg-Trp, 2) raising speculation that the imidazolium and/or indole moieties from peptides having nitrogen heterocycles may be of importance for relaxing the contracted aorta. In order to gain further insight about the effect of vasoactive peptides on the structural requirements of relaxation, we investigated in this study the relaxation behavior of adenine (6-amino-6H-purine) and its analogues on the contracted aorta, since adenine has structural similarity with the side-chains of Trp-His.…”

γ-Glutamylcysteine inhibits oxidative stress in human endothelial cells

“…Therefore, we currently investigate a role of GGC as a cell-penetrating pepide by assessing its cellular uptake using an animal model. Administration of dipeptides influence atherosclerotic development in apo E-deficient mouse models (Matsui et al 2010) and immune responses and mRNA expression of GCS-HS in both humans and mice with compromised immune functions (Murakami et al 2009;Takagi et al 2010). Oligopeptides inhibit TNFα-induced activation of NF-κB in human aortic endothelial cells (Ringseis et al 2009) and ROS formation by inducing the expression of antioxidant enzymes, superoxide dismutase (SOD) and heme oxygenase, in mice (White et al 2009).…”