Dataset Information

Rapeseed protein-derived peptides, LY, RALP, and GHS, modulates key enzymes and intermediate products of renin-angiotensin system pathway in spontaneously hypertensive rat.

ABSTRACT: Rapeseed proteins are a rich source of bioactive peptides. LY, RALP and GHS were previously identified from rapeseed protein hydrolysates as potent ACE and renin inhibiting peptides. In this study, the rapeseed peptides were individually evaluated for their molecular mechanisms and regulatory effects on components of the renin-angiotensin system in spontaneously hypertensive rats (SHR), including the mRNA and/or protein levels of angiotensin-converting enzyme (ACE), renin, ACE2, angiotensin II and angiotensin-(1-7) in myocardial tissues. Oral administration of 30?mg peptides/kg body weight every 2 days for five weeks significantly decreased the systolic blood pressure and the myocardial mRNA and protein levels of ACE and renin in SHR. LY, RALP and GHS also increased the expression of ACE2, angiotensin-(1-7) and Mas receptor levels, which may have mediated their antihypertensive activity. Dipeptide LY also inhibited angiotensin II protein expression in the heart tissue. Taken together, the finding demonstrates the multi-target physiological effects of the rapeseed peptides, beyond ACE and renin inhibition, which enhances knowledge of the antihypertensive mechanisms of food protein-derived peptides.

SUBMITTER: He R

PROVIDER: S-EPMC6550218 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Rapeseed protein-derived peptides, LY, RALP, and GHS, modulates key enzymes and intermediate products of renin-angiotensin system pathway in spontaneously hypertensive rat.

He Rong R Yang Yi-Jie YJ Wang Zhigao Z Xing Chang-Rui CR Yuan Jian J Wang Li-Feng LF Udenigwe Chibuike C Ju Xing-Rong XR

NPJ science of food 20190117

Rapeseed proteins are a rich source of bioactive peptides. LY, RALP and GHS were previously identified from rapeseed protein hydrolysates as potent ACE and renin inhibiting peptides. In this study, the rapeseed peptides were individually evaluated for their molecular mechanisms and regulatory effects on components of the renin-angiotensin system in spontaneously hypertensive rats (SHR), including the mRNA and/or protein levels of angiotensin-converting enzyme (ACE), renin, ACE2, angiotensin II a ...[more]

PMID: 31304273

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Project description:There is an ongoing interest in the renin-angiotensin system (RAS) contribution either to pathological mechanisms leading to hypertension (mainly regarding the ACE/AngII/AT1R axis), or, to RAS protective and pro-regenerative actions, primarily ascribed to the mediation of the AT2R and the MAS1 receptor. In the present study, we evaluated the modulation of gene expression and protein levels of "deleterious" (ACE/AngII/AT1R) and "protective" [ACE/AngII/AT2R and ACE2/Ang(1-7)/MAS1 arms] RAS components in parietal and frontal areas of cerebral cortex of spontaneously hypertensive rats (SHRs), after two periods of mandibular extensions (MEs). Blood pressure, BP and heart rate, HR were also measured. While no significant changes in BP and HR were present in the sham operated (SO) group, in rats after two MEs (2-ME rats), BP displayed a marked decrease (p < 0.001) at ME2, and remained then stably low for the subsequent observation period. In gene expression analysis, in SHRs undergoing two MEs, either in parietal or frontal cortex, we did not observe any significant variation of AT2R and ACE2 with respect to SO rats. In contrast, we observed a decrease in Mas1 gene expression in parietal area (p < 0.01) and an increase in frontal region (p < 0.01). AT1R and ACE gene expression was significantly higher in 2-ME rats than SO in parietal cortex (p < 0.05) but no difference was observed in the frontal area. Concerning protein levels, in parietal area, AT1R and AT2R did not change whereas MAS1 significantly decreased in 2-ME rats (p < 0.05). In frontal area, both AT1R and AT2R significantly decreased in 2-ME rats (p < 0.05), whereas MAS1 did not significantly change. Gene expression analysis in normotensive (NT) rats revealed the non-detectability of AT1R in both parietal and frontal zone. In parietal area, AT2R (p < 0.0001) and Mas1 (p < 0.01) were significantly decreased in 2-ME NT rats, when compared to SO, and ACE and ACE2 resulted not detectable whereas there was some expression of these genes after 2-ME procedure. In conclusion, our data in rat models indicated that a 2-ME procedure induced a hypotensive response and that a modulation of gene expression and protein levels of RAS components occurred in different cerebral cortex areas.

Project description:Hypertension is one of the major predisposing factors for neurodegenerative disease characterized with activated renin-angiotensin system (RAS) in both periphery and brain. Vitamin D (VitD) is recently recognized as a pleiotropic hormone with strong neuroprotective properties. While multiple lines of evidence suggest that VitD can act on RAS, the evidence concerning the crosstalk between VitD and RAS in the brain is limited. Therefore, this study aims to evaluate whether VitD can modulate brain RAS to trigger neuroprotective actions in the brain of spontaneously hypertensive rats (SHR). Our data showed that calcitriol treatment induced VDR expression and inhibited neural death in the prefrontal cortex of SHR. Sustained calcitriol administration also inhibited microglia M1 polarization, but enhanced M2 polarization, accompanied with decreased expression of proinflammatory cytokines. We then further explored the potential mechanisms and showed that SHR exhibited overactivated classical RAS with increased expression of angiotensin II (Ang II) receptor type 1 (AT1), angiotensin converting enzyme (ACE) and Ang II production, whereas the counteracting arm of traditional RAS, ACE2/Ang(1-7)/MasR, was impaired in the SHR brain. Calcitriol nonsignificantly suppressed AT1 and ACE but markedly reduced Ang II formation. Intriguingly, calcitriol exerted pronouncedly impact on ACE2/Ang(1-7)/MasR axis with enhanced expression of ACE2, MasR and Ang(1-7) generation. Meanwhile, calcitriol ameliorated the overactivation of NADPH-oxidase (Nox), the downstream of RAS, in SHR, and also mitigated oxidative stress. In microglial (BV2) cells, we further found that calcitriol induced ACE2 and MasR with no significant impact on ACE and AT1. In accordance, calcitriol also attenuated Ang II-induced Nox activation and ROS production, and shifted the microglia polarization from M1 to M2 phenotype. However, co-treatment with A779, a specific MasR antagonist, abrogated the antioxidant and neuroimmune modulating actions of VitD. These findings strongly indicate the involvement of ACE2/Ang(1-7)/MasR pathway in the neuroprotective mechanisms of VitD in the hypertensive brain.

Project description:BackgroundTaiwan has the highest renal disease incidence and prevalence in the world. We evaluated the association of statin and renin-angiotensin system inhibitor (RASI) use with dialysis risk in hypertensive patients.MethodsOf 248,797 patients who received a hypertension diagnosis in Taiwan during 2001-2012, our cohort contained 110,829 hypertensive patients: 44,764 who used RASIs alone; 7,606 who used statins alone; 27,836 who used both RASIs and statins; and 33,716 who used neither RASIs or statins. We adjusted for the following factors to reduce selection bias by using propensity scores (PSs): age; sex; comorbidities; urbanization level; monthly income; and use of nonstatin lipid-lowering drugs, metformin, aspirin, antihypertensives, diuretics, and beta and calcium channel blockers. The statin and RASI use index dates were considered the hypertension confirmation dates. To examine the dose-response relationship, we categorized only statin or RASI use into four groups in each cohort: <28 (nonusers), 28-90, 91-365, and >365 cumulative defined daily doses (cDDDs).ResultsIn the main model, PS-adjusted hazard ratios (aHRs; 95% confidence intervals [CIs]) for dialysis risk were 0.57 (0.50-0.65), 0.72 (0.53-0.98), and 0.47 (0.41-0.54) in the only RASI, only statin, and RASI + statin users, respectively. RASIs dose-dependently reduced dialysis risk in most subgroups and in the main model. RASI use significantly reduced dialysis risk in most subgroups, regardless of comorbidities or other drug use (P < 0.001). Statins at >365 cDDDs protected hypertensive patients against dialysis risk in the main model (aHR = 0.62, 95% CI: 0.54-0.71), regardless of whether a high cDDD of RASIs, metformin, or aspirin was used.ConclusionStatins and RASIs independently have a significant dose-dependent protective effect against dialysis risk in hypertensive patients. The combination of statins and RASIs can additively protect hypertensive patients against dialysis risk.

Dataset Information

Rapeseed protein-derived peptides, LY, RALP, and GHS, modulates key enzymes and intermediate products of renin-angiotensin system pathway in spontaneously hypertensive rat.

Publications

Rapeseed protein-derived peptides, LY, RALP, and GHS, modulates key enzymes and intermediate products of renin-angiotensin system pathway in spontaneously hypertensive rat.

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