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

  • Toshiro Matsui (a1), Masao Sato (a1), Mitsuru Tanaka (a1), Yasuna Yamada (a1), Shimpei Watanabe (a1), Yumiko Fujimoto (a1), Katsumi Imaizumi (a1) and Kiyoshi Matsumoto (a1)...

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.

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Corresponding author

*Corresponding author: Dr Toshiro Matsui, fax +81 92 642 3012, email tmatsui@agr.kyushu-u.ac.jp

References

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1Kawasaki, T, Seki, E, Osajima, K, et al. (2000) Antihypertensive effect of valyl-tyrosine, a short chain peptide derived from sardine muscle hydrolyzate, on mild hypertensive subjects. J Hum Hypertens 14, 519523.
2Hata, Y, Yamamoto, M, Ohni, M, et al. (1996) A placebo-controlled study of the effect of sour milk on blood pressure in hypertensive subjects. Am J Clin Nutr 64, 767771.
3Matsufuji, H, Matsui, T, Ohshige, S, et al. (1995) Antihypertensive effects of angiotensin fragments in SHR. Biosci Biotechnol Biochem 59, 13981401.
4Matsui, T, Hayashi, A, Tamaya, K, et al. (2003) Depressor effect induced by dipeptide, Val-Tyr, in hypertensive transgenic mice is due, in part, to the suppression of human circulating renin-angiotensin system. Clin Exp Pharm Phys 30, 262265.
5Matsui, T, Ueno, T, Tanaka, M, et al. (2005) Antiproliferation action of an angiotensin I-converting enzyme inhibitory peptides, Val-Tyr, via an L-type Ca2+ channel inhibition in cultured vascular smooth muscle cells. Hypertens Res 28, 545552.
6Tanaka, M, Matsui, T, Ushida, Y, et al. (2006) Vasodilating effect of di-peptides in thoracic aortas from spontaneously hypertensive rats. Biosci Biotechnol Biochem 70, 22922295.
7Tanaka, M, Tokuyasu, M, Matsui, T, et al. (2008) Endothelium-independent vasodilation effect of di- and tri-peptides in thoracic aorta of Sprague–Dawley rats. Life Sci 82, 869875.
8Masuda, O, Nakamura, Y & Takano, T (1996) Antihypertensive peptides are present in aorta after oral administration of sour milk containing these peptides to spontaneously hypertensive rats. J Nutr 126, 30633068.
9Erdmann, K, Grosser, N, Schipporeit, K, et al. (2006) The ACE inhibitory dipeptide Met-Tyr diminished free radical formation in human endothelial cells via induction of heme oxygenase-1 and ferritin. J Nutr 136, 21482152.
10Navab, M, Anantharamaiah, GM, Reddy, ST, et al. (2005) Oral small peptides render HDL anti-inflammatory in mice and monkeys and reduce atherosclerosis in apoE null mice. Circ Res 97, 524532.
11Ni, W, Tsuda, Y, Sakono, M, et al. (1998) Dietary soy protein isolate, compared with casein, reduces atherosclerotic lesion area in apolipoprotein E-deficient mice. J Nutr 128, 18841889.
12Sato, M, Shibata, K, Nomura, R, et al. (2005) Linoleic acid-rich fats reduce atherosclerosis development beyond its oxidative and inflammatory stress-increasing effect in apolipoprotein E-deficient mice in comparison with saturated fatty acid-rich fats. Br J Nutr 94, 896901.
13Paigen, B, Morrow, A, Holmes, PA, et al. (1987) Quantitative assessment of atherosclerotic lesions in mice. Atherosclerosis 68, 231240.
14Tangirala, RK, Rubin, EM & Palinski, W (1998) Quantification of atherosclerosis in murine models: correlation between lesions in the aortic origin and in the entire aorta, and differences in the extent of lesions between sexes in LDL. J Lipid Res 36, 23202328.
15Brown, L, Rosner, B, Willett, WW, et al. (1999) Cholesterol-lowering effect of dietary fiber: a meta-analysis. Am J Clin Nutr 69, 3042.
16Auclair, S, Silberberg, M, Gueux, E, et al. (2008) Apple polyphenols and fibers attenuate atherosclerosis in apolipoprotein E-deficient mice. J Agric Food Chem 56, 55585563.
17Matchett, MD, MacKinnon, SL, Sweeney, MI, et al. (2006) Inhibition of matrix metalloproteinase activity in DU145 human prostate cancer cells by flavonoids from lowbush blueberry (Vaccinium angustifolium): possible roles for protein kinase C and mitogen-activated protein-kinase-mediated events. J Nutr Biochem 17, 117125.
18Oak, HH, Bedoui, JEI, Anglard, P, et al. (2004) Red wine polyphenolic compounds strongly inhibit pro-matrix metalloprotease-2 expression and its activation in response to thrombin via direct inhibition of membrane type-1-matrix metalloproteinase in vascular smooth muscle cells. Circulation 110, 18611867.
19Matsumoto, M, Sata, M, Fukuda, D, et al. (2008) Orally administered eicosapentanoic acid reduces and stabilizes atherosclerotic lesions in apoE-deficient mice. Atherosclerosis 197, 524533.
20Nagarajan, S, Burris, RL, Stewart, BW, et al. (2008) Dietary soy protein isolate ameliorates atherosclerotic lesions in apolipoprotein E-deficient mice potentially by inhibiting monocyte chemoattractant protein-1 expression. J Nutr 138, 332337.
21Cho, SJ, Juillerat, MA & Lee, CH (2007) Cholesterol lowering mechanism of soybean protein hydrolysate. J Agric Food Chem 55, 1059910604.
22Nagaoka, S, Futamura, Y, Miwa, K, et al. (2001) Identification of novel hypocjolesterolemic peptides derived from bovine milk β-lactoglobulin. Biochem Biophys Res Commun 281, 1117.
23Yamauchi, R, Ohinata, K & Yoshikawa, M (2003) β-Lactotensin and nerotensin rapidly reduce serum cholesterol via NT2 receptor. Peptides 24, 19551961.
24Deng, YM, Wu, BJ, Witting, PK, et al. (2004) Probucol protects against smooth muscle cell proliferation by upregulating heme oxygenase-1. Circulation 110, 18551860.
25Miguel, M, Alvarez, Y, Fandino, RL, et al. (2007) Vasodilator effects of peptides derived from egg white proteins. Regulatory Peptides 140, 131135.
26Mishra, S & Hermsmeyer, K (1994) Selective inhibition of T-type Ca2+ channels by Ro40-5967. Circ Res 75, 144148.
27Nakashima, Y, Plump, AS, Raines, EW, et al. (1994) ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler Thromb Vasc Biol 14, 133140.
28Cabassi, A, Vinci, S, Cantoni, AM, et al. (2002) Sympathetic activation in adipose tissue and skeletal muscle of hypertensive rats. Hypertension 39, 656661.
29Uguccioni, M, Gionchetti, P, Robbiani, DF, et al. (1999) Circulating levels of ICAM-1, VCAM-1, and MCP-1 are increased in haemodialysis patients: association with inflammation, dyslipidaemia, and vascular events. Am J Pathol 155, 331336.
30Takeya, M, Yoshimura, T, Leonard, EJ, et al. (1993) Detection of monocyte chemoattractant protein-1 in human atherosclerotic lesions by an anti-monocyte chemoattractant protein-1 monoclonal antibody. Hum Pathol 24, 534539.
31Nakano, K, Egashira, K, Ohtani, K, et al. (2008) Azelnidipine has anti-atherosclerotic effects independent of its blood pressure-lowering actions in monkeys and mice. Atherosclerosis 196, 172179.

Keywords

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

  • Toshiro Matsui (a1), Masao Sato (a1), Mitsuru Tanaka (a1), Yasuna Yamada (a1), Shimpei Watanabe (a1), Yumiko Fujimoto (a1), Katsumi Imaizumi (a1) and Kiyoshi Matsumoto (a1)...

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