title: Milk-derived peptides, Val-Pro-Pro and Ile-Pro-Pro, attenuate atherosclerosis development in apolipoprotein e-deficient mice: a preliminary study.
abstract: Milk-derived peptides, Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP), have angiotensin I-converting enzyme inhibitory activities and blood pressure-lowering effects. We examined the effects of these peptides on the development of atherosclerosis in apolipoprotein E-deficient [apoE(-/-)] mice. For 31 weeks, six-week-old male apoE(-/-) mice received a diet that included one of the following: fermented milk containing both VPP and IPP; casein hydrolysate containing both of these peptides; synthesized VPP; synthesized IPP; enalapril; captopril; or control diet. At the end of feeding, blood biochemistry, aortic atherogenesis, and gene expression by DNA microarray analysis were evaluated. There were no significant changes in the plasma lipid levels and 8-isoprostane, a marker of oxidative stress. The area ratio of intima to media in the aortic arch was significantly lower in the fermented milk, casein hydrolysate, synthesized VPP, enalapril, and captopril groups than in the control group. As is common with diets containing VPP and/or IPP, we observed reductions in mRNA expression of inflammatory cytokines, such as interleukin (IL)-6 and IL-1β, oxidized low-density lipoprotein receptor, and transcription regulators. These results suggest that a continuous intake of VPP and IPP might be beneficial for preventing atherosclerosis caused by hypercholesterolemia.
authors: Microbiology & Fermentation Laboratory, Calpis Co., Ltd., Kanagawa, Japan. teppei.nakamura@calpis.co.jp
authors: Teppei
authors: T
authors: Nakamura
authors: Tatsuhiko
authors: T
authors: Hirota
authors: Katsura
authors: K
authors: Mizushima
authors: Kohji
authors: K
authors: Ohki
authors: Yuji
authors: Y
authors: Naito
authors: Naoyuki
authors: N
authors: Yamamoto
authors: Toshikazu
authors: T
authors: Yoshikawa
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008892:Milk / Q000737:chemistry*; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry; D011492:Protein Hydrolysates / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D001057:Apolipoproteins E; D053583:Interleukin-1beta; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D009842:Oligopeptides; D011492:Protein Hydrolysates; C489032:isoleucyl-prolyl-proline; C099252:oxidized low density lipoprotein; C489031:valyl-prolyl-proline