Study of the mechanism of antihypertensive peptides VPP and IPP in spontaneously hypertensive rats by DNA microarray analysis

Yamaguchi, Naoya; Kawaguchi, Kyosuke; Yamamoto, Naoyuki

doi:10.1016/j.ejphar.2009.08.005

Cited by 76 publications

(60 citation statements)

References 38 publications

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“…The gene eNOS is associated with NO synthesis and was upregulated in the H9 group in our study. This result is in accordance with the results reported by Yamaguchi et al (2009) that showed eNOS was upregulated in SHRs fed with antihypertensive peptides. eNOS catalyzes the synthesis of nitric oxide in blood vessels and is involved in regulating vascular tone and platelet aggregation; an increase in eNOS expression reduced hypertension in fructose-treated rats (Zhao et al 2009).…”

Section: Discussionsupporting

confidence: 83%

“…eNOS catalyzes the synthesis of nitric oxide in blood vessels and is involved in regulating vascular tone and platelet aggregation; an increase in eNOS expression reduced hypertension in fructose-treated rats (Zhao et al 2009). Unlike the report of Yamaguchi et al (2009), we did not find differential expression of the gene connexin 40 but did find differential expression of Nfkb1 and Slc4a7, which were also upregulated in H9 group compared with the control. Nfkb1 is a transcription factor and binding of Nfkb1 subunits p50 and p65 to the eNOS promoter can increase eNOS transcription (Davis et al 2004).…”

Section: Discussioncontrasting

confidence: 55%

“…The upregulation of eNOS and PPARγ genes after the long-term intake of milk fermented by L. helveticus H9 may in turn result in an increase in the activity and bioavailability of NO to heart tissue, which may partially explain the antihypertensive effect of fermented milk. But in the report of Yamaguchi et al (2009), the expression of PPARγ gene was decreased in the aorta of SHRs after repeated administration of Val-Pro-Pro and Ile-Pro-Pro; this contradiction is puzzling and need more verification.…”

Section: Discussionmentioning

confidence: 99%

“…Many studies reported the bioactive peptides Val-Pro-Pro and Ile-Pro-Pro in fermented milk were responsible for the antihypertensive effect, and the gene expression profile in the aorta of SHRs was detected after repeated administration of Val-ProPro and Ile-Pro-Pro (Yamaguchi et al 2009), but we paid more attention on blood pressure and less on the left ventricular hypertrophy. Here, we have shown that some genes associated with hypertension are regulated by provision of milk fermented by L. helveticus H9 and that this may indeed be responsible for the observed antihypertensive effect and relief from left ventricular hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

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DNA microarray analysis of the antihypertensive effect of milk fermented by Lactobacillus helveticus H9 on spontaneously hypertensive rats

Chen

Zhong

Xue

et al. 2015

Dairy Sci. & Technol.

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Although an antihypertensive effect of fermented milk has been demonstrated in many human and animal experiments, the molecular mechanism controlling it is still poorly understood. In this study, we used DNA microarray analysis to determine the molecular mechanism of the antihypertensive effect of fermented milk. The results showed that gene expression in the left ventricle of spontaneously hypertensive rats was regulated when milk fermented by Lactobacillus helveticus (L. helveticus) H9 was administered. Some hypertension-associated genes were differentially expressed. Indepth analysis showed that these differentially expressed genes were related to NO synthesis, cell proliferation, endothelin binding, and blood clot breakdown. These processes could be responsible for the antihypertensive response and relief of left ventricular hypertrophy observed. It is likely that regulation of the gene expression of endothelial nitric oxide synthase (eNOS), peroxisome proliferator-activated receptor γ (PPARγ), endothelin type A receptor (Ednra), and other hypertension-associated genes play an important role in these processes. In summary, this study provided valuable information that contributes to our understanding of the molecular mechanisms by which antihypertensive effects are provided from milk fermented by L. helveticus H9.

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Section: Discussionsupporting

confidence: 83%

Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

DNA microarray analysis of the antihypertensive effect of milk fermented by Lactobacillus helveticus H9 on spontaneously hypertensive rats

Chen

Zhong

Xue

et al. 2015

Dairy Sci. & Technol.

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“…Yamaguchi et al (69) investigated the effects of tripeptides on aortic gene expression by giving pure tripeptides to SHR for 5 d. Changes in gene expression were not large in this study either, but significant up-regulation of eNOS and connexin-40 genes were detected. We observed quite opposite effects, as both these two genes were rather down-than up-regulated in the present study.…”

Section: Discussionmentioning

confidence: 50%

High blood pressure-lowering and vasoprotective effects of milk products in experimental hypertension

et al. 2011

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Milk casein-derived angiotensin-converting enzyme (ACE)-inhibitory tripeptides isoleucine-proline-proline (Ile-Pro-Pro) and valineproline-proline (Val-Pro-Pro) have been shown to have antihypertensive effects in human subjects and to attenuate the development of hypertension in experimental models. The aim of the present study was to investigate the effect of a fermented milk product containing Ile-Pro-Pro and Val-Pro-Pro and plant sterols on already established hypertension, endothelial dysfunction and aortic gene expression. Male spontaneously hypertensive rats (SHR) with baseline systolic blood pressure (SBP) of 195 mmHg were given either active milk (tripeptides and plant sterols), milk or water ad libitum for 6 weeks. SBP was measured weekly by the tail-cuff method. The endothelial function of mesenteric arteries was investigated at the end of the study. Aortas were collected for DNA microarray study (Affymetrix Rat Gene 1.0 ST Array). The main finding was that active milk decreased SBP by 16 mmHg compared with water (178 (SEM 3) v. 195 (SEM 3) mmHg; P,0·001). Milk also had an antihypertensive effect. Active milk improved mesenteric artery endothelial dysfunction by NOdependent and endothelium-derived hyperpolarising factor-dependent mechanisms. Treatment with active milk caused mild changes in aortic gene expression; twenty-seven genes were up-regulated and eighty-two down-regulated. Using the criteria for fold change (fc) , 0·833 or . 1·2 and P,0·05, the most affected (down-regulated) signalling pathways were hedgehog, chemokine and leucocyte transendothelial migration pathways. ACE expression was also slightly decreased (fc 0·86; P¼ 0·047). In conclusion, long-term treatment with fermented milk enriched with tripeptides and plant sterols decreases SBP, improves endothelial dysfunction and affects signalling pathways related to inflammatory responses in SHR.Key words: Milk-derived bioactive peptides: Experimental hypertension: Spontaneously hypertensive rats: Plant sterols: Endothelial function Hypertension is one of the most important risk factors for CHD, heart failure, cerebrovascular disease and chronic kidney disease. The prevalence of hypertension is increasing worldwide, both in developed and developing countries (1) . Up to 30 % of the world's adult population was estimated to have hypertension in 2000 (2) . Any reductions in blood pressure, however small, are meaningful; a systolic blood pressure (SBP) reduction of 9 mmHg and a diastolic blood pressure reduction of 5 mmHg reduce the risk of stroke by [35][36][37][38][39][40] .Besides pharmacological therapy, lifestyle and nutritional factors play a significant role in the prevention and treatment of hypertension and related disorders. Low saturated fat and Na intake and increased consumption of K, Ca and soluble fibre positively affect blood pressure (4) . Plant sterols and stanols (also called as phytosterols and -stanols) have wellestablished cholesterol-lowering effects. The consumption of 2 g plant sterols per d has been shown to lowe...

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Functional Food Products with Antihypertensive Effects

Yamamoto¹

2010

Bioactive Proteins and Peptides as Functional Foods and Nutraceuticals

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Study of the mechanism of antihypertensive peptides VPP and IPP in spontaneously hypertensive rats by DNA microarray analysis

Cited by 76 publications

References 38 publications

DNA microarray analysis of the antihypertensive effect of milk fermented by Lactobacillus helveticus H9 on spontaneously hypertensive rats

DNA microarray analysis of the antihypertensive effect of milk fermented by Lactobacillus helveticus H9 on spontaneously hypertensive rats

High blood pressure-lowering and vasoprotective effects of milk products in experimental hypertension

Functional Food Products with Antihypertensive Effects

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