scholarly journals Study on Toll-Like Receptor 2-Mediated Inflammation-Induced Familial Hypertension Combined with Hyperlipemia and Its Mechanism

2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Jia Liu ◽  
Chunjing Li ◽  
Qiuyang Wang ◽  
Haiyan Hu ◽  
Chunhong Li ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Lipid ◽  
Normal Group ◽  
Inflammatory Factors ◽  
Control Group ◽  
Ang Ii ◽  
Toll Like Receptor ◽  
High Fat ◽  
In The Wild ◽  
Toll Like Receptor 2

According to the latest clinical data, cardiovascular diseases have ranked first in prone diseases, causing 40% of the premature deaths of China’s population. This study aimed to investigate the influence of Toll-like receptor 2- (TLR2-) mediated inflammation on the occurrence and development of familial hypertension combined with hyperlipemia and its related mechanism. Blood specimens from 66 patients undergoing coronary atherosclerosis were collected and grouped, including 22 patients into the control group, 25 into the familial hypertension group, and 19 into familial hypertension combined with hyperlipemia group. In this study, ELISA was conducted for determining the levels of four inflammatory factors of TLR2 and IL-1β, IL-6, TNF-ɑ, and CCL2 in serum and the levels of relevant indicators in mice. C57Bl/6j and genetically engineered C.129(B6)-Tlr2tm1Kir/J mice were given subcutaneous injection of normal saline (wild-saline group), 8-week 40% high-fat diet (wild-high-fat group), and subcutaneous Alzet-implanted angiotensin II micropump supplemented with the research diet (wild-high fat-Ang II group, Tlr2-/--high fat-Ang II group). Blood pressure in mice was recorded consecutively with a noninvasive hemopiezometer for eight weeks. TLR2 and IL-1β, IL-6, TNF-ɑ, and CCL2 in serum of patients with familial hypertension combined with hyperlipemia and the hypertension combined with hyperlipemia mouse model were higher than those in the normal group. Under combined intervention of Ang II and the research diet, mRNA expression related to blood pressure, blood lipid, and fat metabolism in Tlr2-/- genetically engineering mice was significantly lower than that in the wild-high fat-Ang II group. The phosphorylation levels of AKT, IKK, and p65 in mice with hypertension combined with hyperlipidemia were significantly higher than those in normal group. The levels of blood pressure and blood lipid in mice after blocking the AKT or NF-κB pathway were significantly downregulated compared with those in the wild-high fat-Ang II group, with statistically significant differences (both P < 0.05 ). In conclusion, TLR2 regulates inflammation through Akt-NF-κB pathway, thus inducing the occurrence and development of familial hypertension combined with hyperlipemia.

scholarly journals Effects of combined use of atorvastatin and losartan in treating patients with diabetic nephropathy

2018 ◽  
Vol 16 ◽  
pp. 205873921879670
Author(s):  
Chao Ding ◽  
Xiaohua Hu
Keyword(s):  
Diabetic Nephropathy ◽  
Endothelial Function ◽  
Cardiovascular Events ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
Inflammatory Factors ◽  
Control Group ◽  
Vascular Endothelial ◽  
Observation Group ◽  
Vascular Endothelial Function

This study is to investigate the effect of atorvastatin combined with losartan on inflammatory factors, vascular endothelial function, and cardiovascular events in patients with diabetic nephropathy. A total of 128 patients with diabetic nephropathy treated in our hospital from January 2014 to December 2015 were selected as the study subjects, and 64 cases were randomly divided into observation group and 64 cases in the control group. The control group was treated with losartan on the basis of routine treatment, and the observation group was treated with atorvastatin on the basis of the control group. The blood lipid, inflammatory factors, changes in vascular endothelial function and cardiovascular events were compared between the two groups. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were not significantly different between the two groups before treatment ( P > 0.05); after treatment, the levels of TC, TG, and LDL-C in the observation group were significantly lower than those of the control group, and the level of HDL-C was significantly higher than that of the control group ( P < 0.05). The levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) were not statistically different between the two groups before treatment ( P > 0.05); after treatment, the levels of hs-CRP, TNF-α, and IL-6 in the observation group were significantly lower than those of the control group ( P < 0.05), the level of HDL-C was significantly higher than that of the control group ( P < 0.05). There were no significant differences in the levels of endothelin-1 (ET-1) and nitric oxide (NO) between the two groups before treatment ( P > 0.05). After treatment, the level of ET-1 in the observation group was significantly lower than that of the control group ( P < 0.05), and the level of NO was significantly higher than that of the control group ( P < 0.05). After treatment, all patients were followed up for 2 years, and the incidence of secondary cardiovascular events in the observation group was 12.50% (8/64), which was significantly lower than 29.69% (19/64) of the control group ( P < 0.05). Combination of atorvastatin and losartan can significantly improve the levels of blood lipid, inflammatory factors, and vascular endothelial function in patients with diabetic nephropathy and can effectively reduce the incidence of cardiovascular events.

scholarly journals Adipokiny, insulinorezistentnost' i aktivnost' simpato-adrenalovoy sistemy u yunoshey s ozhireniem, manifestirovavshim v pubertatnyy period

2012 ◽  
Vol 9 (2) ◽  
pp. 49-52 ◽  
Author(s):  
A F Verbovoy ◽  
E V Mitroshina ◽  
Yu A Dolgih
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Young Men ◽  
Blood Lipid ◽  
The Other ◽  
Control Group ◽  
Normal Blood Pressure ◽  
Sympathoadrenal System ◽  
Increased Activity ◽  
Lipid Spectrum

69 young men with obesity manifesting at puberty have been examined. The average age was 19,22±0,26. 17 healthy young men, whose average age was 22 ± 0,72 years old, constituted a control group. The examined were divided according to their blood pressure (BP): the first subgroup included 36 young men with normal blood pressure, the other subgroup included 33 young men with arterial hypertension. Levels of blood lipid spectrum, levels of leptin, resistin, adiponectin, insulin in serum, urinary metanephrine excretion were measured. We obtained the following results: young men with obesity identified atherogenic changes in lipid metabolism, insulin resistance and compensatory hyperinsulinemia. Regardless of the level of blood pressure they showed a significant increase in leptin levels. In the subgroup of patients with hypertension we found increased urinary excretion of metanephrine, indicating increased activity of the sympathoadrenal system and its involvement in the formation of hypertension. The level of adiponectin in the surveyed tended to decrease, more pronounced in the combination of obesity and hypertension.

Effect of chronic dietary treatment with L-tryptophan on the maintenance of hypertension in spontaneously hypertensive rats

1989 ◽  
Vol 67 (6) ◽  
pp. 656-662 ◽  
Author(s):  
Melvin J. Fregly ◽  
Colin Sumners ◽  
J. Robert Cade
Keyword(s):  
Blood Pressure ◽  
Specific Binding ◽  
Dietary Treatment ◽  
Control Group ◽  
Dependent Manner ◽  
Ang Ii ◽  
Urinary Catecholamines ◽  
Spontaneously Hypertensive ◽  
Daily Food ◽  
Elevated Systolic Blood Pressure

Chronic dietary administration of L-tryptophan at 2.5 and 5.0% by weight reduced the elevated systolic blood pressure of spontaneously hypertensive (SH) rats. Blood pressure was reduced significantly by 3 weeks after initiation of treatment and continued to fall during the course of the 15 weeks of treatment. Body weights of the treated rats were not affected significantly by treatment, nor were daily food and fluid intakes and urine outputs. SH rats, treated with the higher dose of tryptophan, also significantly reduced their urinary outputs of epinephrine and norepinephrine compared with SH controls, while both doses of tryptophan increased urinary outputs of dopamine significantly above that of SH controls. Treatment with tryptophan increased significantly the specific binding of [125I]angiotensin II (Ang II) to membranes from the diencephalon in a dose-dependent manner. Measurement of catecholamine concentration of the supernatant from homogenates used for the Ang II binding assay revealed a significant correlation between the specific binding of Ang II to brain membranes of the two tryptophan-treated groups and the concentration of norepinephrine in the supernatant. There was also a significant correlation between the specific binding of Ang II and the concentratiion of dopamine in the supernatant of the control group and the group treated with the higher dose of tryptophan. These results show that chronic dietary administration of tryptophan can reduce the elevated blood pressure of SH rats and support the possibility that this neutral amino acid may act via its effect on the concentration of the neurohormones, norepinephrine and dopamine, in the diencephalon to regulate the binding of Ang II to its receptors.Key words: tryptophan, spontaneous hypertension, brain angiotensin binding, urinary catecholamines.

Abstract P104: Renin Angiotensin System (RAS) Modulation in Hypertension Program by Maternal Intrauterine Malnutrition

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Rafael S Banti ◽  
Rodrigo Yokota ◽  
Danielle S Aragão ◽  
Adriana Souza ◽  
Amanda Pedroso ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renin Angiotensin System ◽  
Control Group ◽  
Ang Ii ◽  
Alternative Pathways ◽  
Angiotensin Peptides ◽  
Increased Risk ◽  
Ace Activity ◽  
Intrauterine Malnutrition ◽  
Group D

Intrauterine malnutrition (IM) during the early stages of development can alter the function of organs and tissues and can predict a lifetime of increased risk for adverse health outcomes, such as diabetes and hypertension. The kidney plays a key role in the development of hypertension programmed by IM, with the participation of the RAS. Our objectives were to study ACE activity and angiotensin peptides levels in tissues. Pregnants Wistar rats were separated into two groups: control group (C), fed ad libitum, and malnourished group (D) submitted to food restriction (diet 50% of the amount of feed consumed by the group C). After birth the offspring were kept as experimental groups C and D, respectively. At 4 months of age, the animals were sacrificed, heart and kidney tissues were collected to quantify angiotensin peptides and ACE activity. The offspring born with low birth weight. Kidney ACE activity was higher in group D compared to group C (299 ±86.7 vs. 253.4 ±84.82 mU/mg, p<0.05), differing from Heart (D versus C: 0.15 ± 0.08 vs. 0.24 ±0.09 mU/mg). Group D presented high blood pressure values compared to group C (140.6 ±2.8 vs. 124,3±2.6 mmHg). Kidney and heart Ang II levels were increased in group D being significant when compared to group C (238.26 ±25.1 vs. 161.85 ±45.6 pmol/g and 397.89±74.9 vs. 223.33±48.7 pmol/g, p<0.05, respectively). The same was observed for Ang I. The vasodilator peptide Ang1-7 levels in group D from kidney and heart were lower in comparison with group C, thus emphasizing an enabling environment for hypertension (220.74 ± 48.74 vs. 288.09 ± 47 pmol/g and 152.1±41.2 pmol/g vs. 228.93±41.2 pmol/g, p<0.05, respectively). Our results indicate that perturbed maternal nutritional status alters tissue RAS resulting in higher blood pressure in the offspring, demonstrated by increased renal ACE activity and Ang II levels, with reduced Ang 1-7. The increase of Ang I and II in the heart, despite low ACE activity in this tissue suggests the activation of RAS alternative pathways. This study describes for the first time that low levels of Ang 1-7 contributed to the early development of hypertension.

Ethanol Extract Combinations Effect of Celery Herb (Apium graveolens L.) and Bay Leaf (Syzygium polyanthum W.) Toward Hypertensive Mice Induced by Sodium Chloride and High Fat Feed

2021 ◽  
Vol 1162 ◽  
pp. 151-158
Author(s):  
Moch. Saiful Bachri ◽  
Widyasari Putranti ◽  
Lina Widiyastuti ◽  
Resalianti Sintiana Devie
Keyword(s):  
Blood Pressure ◽  
Sodium Chloride ◽  
Research Result ◽  
Ethanol Extract ◽  
Apium Graveolens ◽  
Control Group ◽  
High Fat ◽  
Control Group Design ◽  
Group Design ◽  
Hypertension Therapy

The combination of herb medicine is alternative option in hypertension because it has more potential for treatment with complications like hyperlipida. Plant which can be used for anti-hypertension therapy is combination of celery herb (Apium graveolens) and bay leaf ethanol extract (Syzygium polyanthum). This research aims to determine the activity of a combination of celery herb ethanol extract (CHEE) and bay leaf ethanol extract (BLEE) and find out how much the decrease of blood pressure on the combination of both toward hypertension with high fat Wistar mice. The design of this research used an experimental design with pre-post control group design. Hypertensive mice are induced with high fat feed and orally with sodium chloride 8%, then the mice are supplied with combinations extract with the dose of 1.125 ; 6.25 ; 2.25 ; 12.5 and 4.5 ; 25 mg/kg, hydrochlorotiazide 2.25 mg/kg, Simvastatin 0.9 mg/kg, CHEE 4.5 mg/kg, BLEE 25 mg/kg and CMC-Na 0.5%. Research result shows that the combination can decrease systole blood pressure in the 22nd day. The extract combination has anti-hypertension effect (it is able to decrease systole blood pressure ≥ 20 mmHg) and it is not significantly different with normal group (p<0.05). Based on the research, it can be concluded that ethanol extract combination can decrease systole blood pressure with high fat complications after using it for 22 days.

Serum apolipoprotein A-1 is related to inflammatory factors in the acute phase of gout

2020 ◽  
Author(s):  
Baoyu Zhang ◽  
Yuan Wang ◽  
Xiaoxia Jia ◽  
Lin Mu ◽  
Xiaobo Wang
Keyword(s):  
Uric Acid ◽  
Blood Glucose ◽  
Acid Level ◽  
Serum Uric Acid Level ◽  
Blood Lipid ◽  
Inflammatory Factors ◽  
Control Group ◽  
Apolipoprotein A ◽  
Increase Blood Glucose ◽  
Liver And Kidney

Abstract BACKGROUNDTo observe the correlation between serum apolipoprotein A-1(apoA-1) and inflammatory factors in patients with gouty arthritis. METHODSFrom February to September 2020, 97 patients with gout (gout group) and 70 healthy controls (control group) were selected as the study subjects，who were admitted to the outpatient department of Beijing lu he hospital affiliated to capital medical university.97 patients in the gout group were in the acute phase. Serum concentrations of apoA-1, NLRP3 inflammasome （NACHT-LRR-PYD protein 3,NLRP3), interleukin-1 (IL-1) and interleukin-9 (IL-9) were detected. The correlation of serum apoA-1 concentration, gout related inflammatory factors (NLRP3, IL-1 beta, IL-9) and other clinical and laboratory indicators was analyzed. RESULTSThe serum apoA-1 concentration in the gout group was lower than that in the control group (P<0.05). With the increase of serum uric acid level, serum apoA-1 concentration decreased（R2=-0.3160，P<0.05）. Multiple linear analyses were performed to increase blood glucose, blood lipid, liver and kidney, etc, and the correlation remained（OR=-3.36，P<0.05）. With the increase of serum IL-1 beta concentration, serum apoA-1 concentration decreased（R2=-0.3993，P<0.05）. Multiple linear analyses were performed to increase blood glucose, blood lipid, liver and kidney, etc., and the correlation remained（OR=-2.95，P<0.05）. CONCLUSIONSIn the acute stage of gout, as the serum uric acid level increases, the serum IL-1β concentration increases and the apoA-1 concentration gradually decreases, which may indicate that apoA-1 participates in the inflammatory response of gout to a certain extent.

Abstract P041: Proximal Tubule-specific Deletion Of Angiotensin Ii Type 1a Receptors In The Kidney Lowers Basal Blood Pressure And Attenuates Angiotensin Ii-induced Hypertension By Increasing Glomerular Filtration And The Pressure-natriuresis Response

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Xiao C Li ◽  
Ana P Leite ◽  
Liang Zhang ◽  
Jia L Zhuo
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Pressor Response ◽  
Control Group ◽  
Ang Ii ◽  
Induced Hypertension ◽  
Basal Blood Pressure ◽  
Pressure Natriuresis ◽  
Specific Deletion

The present study tested the hypothesis that intratubular angiotensin II (Ang II) and AT 1a receptors in the proximal tubules of the kidney plays an important role in basal blood pressure control and in the development of Ang II-induced hypertension. Mutant mice with proximal tubule-specific deletion of AT 1a receptors in the kidney, PT- Agtr1a -/- , were generated to test the hypothesis. Eight groups (n=7-12 per group) of adult male wild-type (WT) and PT- Agtr1a -/- mice were infused with or without Ang II for 2 weeks (1.5 mg/kg, i.p.). Basal systolic, diastolic, and mean arterial pressures were ~13 ± 3 mmHg lower in PT- Agtr1a -/- than WT mice ( P <0.01). Basal glomerular filtration rate (GFR), as measured using transdermal FITC-sinistrin, was significantly higher in PT- Agtr1a -/- mice (WT: 160.4 ± 7.0 μl/min vs. PT- Agtr1a -/- : 186.0 ± 6.0 μl/min, P <0.05). Basal 24 h urinary Na + excretion (U Na V) was significantly higher in PT- Agtr1a -/- than WT mice ( P <0.01). In response to Ang II infusion, both WT and PT- Agtr1a -/- mice developed hypertension, and the magnitude of the pressor response to Ang II was similar in WT (Δ43 ± 3 mmHg, P <0.01) and PT- Agtr1a -/- mice (Δ39 ± 5 mmHg, P <0.01). However, the absolute blood pressure level was still 16 ± 3 mmHg lower in PT- Agtr1a -/- mice ( P <0.01). Ang II significantly decreased GFR to 132.2 ± 7.0 μl/min in WT mice ( P <0.01), and to 129.4 ± 18.6 μl/min in PT- Agtr1a -/- mice ( P <0.01), respectively. In WT mice, U Na V increased from 139.3 ± 22.3 μmol/24 h in the control group to 196.4 ± 29.6 μmol/24 h in the Ang II-infused group ( P <0.01). In PT- Agtr1a -/- mice, U Na V increased from 172.0 ± 10.2 μmol/24 h in the control group to 264.7 ± 35.4 μmol/24 h in the Ang II-infused group ( P <0.01). The pressor response to Ang II was attenuated, while the natriuretic response was augmented by losartan in WT and PT- Agtr1a -/- mice ( P <0.01). Finally, proximal tubule-specific deletion of AT 1a receptors significantly augmented the pressure-natriuresis response and natriuretic responses to acute saline infusion ( P <0.01) or a 2% high salt diet ( P <0.01). We concluded that deletion of AT 1a receptors selectively in the proximal tubules lowers basal blood pressure and attenuates Ang II-induced hypertension by increasing GFR and promoting the natriuretic response in PT- Agtr1a -/- mice.

scholarly journals Interleukin-9 Deletion Relieves Vascular Dysfunction and Decreases Blood Pressure via the STAT3 Pathway in Angiotensin II-Treated Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Yunzhao Yang ◽  
Shaoqun Tang ◽  
Chunchun Zhai ◽  
Xin Zeng ◽  
Qingjian Liu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Inflammatory Response ◽  
Vascular Dysfunction ◽  
Control Group ◽  
Dependent Manner ◽  
Ang Ii ◽  
Stat3 Pathway

Background. Multiple interleukin (IL) family members were reported to be closely related to hypertension. We aimed to investigate whether IL-9 affects angiotensin II- (Ang II-) induced hypertension in mice. Methods. Mice were treated with Ang II, and IL-9 expression was determined. In addition, effects of IL-9 knockout (KO) on blood pressure were observed in Ang II-infused mice. To determine whether the effects of IL-9 on blood pressure was mediated by the signal transducer and activator of the transcription 3 (STAT3) pathway, Ang II-treated mice were given S31-201. Furthermore, circulating IL-9 levels in patients with hypertension were measured. Results. Ang II treatment increased serum and aortic IL-9 expression in a dose-dependent manner; IL-9 levels were the highest in the second week and continued to remain high into the fourth week after the treatment. IL-9 KO downregulated proinflammatory cytokine expression, whereas it upregulated anti-inflammatory cytokine levels, relieved vascular dysfunction, and decreased blood pressure in Ang II-infused mice. IL-9 also reduced smooth muscle 22α (SM22α) expression and increased osteopontin (OPN) levels both in mice and in vitro. The effects of IL-9 KO on blood pressure and inflammatory response were significantly reduced by S31-201 treatment. Circulating IL-9 levels were significantly increased in patients with the hypertension group than in the control group, and elevated IL-9 levels positively correlated with both systolic blood pressure and diastolic blood pressure in patients with hypertension. Conclusions. IL-9 KO alleviates inflammatory response, prevents phenotypic transformation of smooth muscle, reduces vascular dysfunction, and lowers blood pressure via the STAT3 pathway in Ang II-infused mice. IL-9 might be a novel target for the treatment and prevention of clinical hypertension.

scholarly journals β-arrestin-2 up-regulates toll-like receptor 2 signaling and inhibits apoptosis in human endometrial cancer heterotransplants in nude mice

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Fanling Hong ◽  
Yujun Zhang ◽  
Wenjin Cheng ◽  
Xiuli Sun ◽  
Jianliu Wang
Keyword(s):  
Inflammatory Cytokines ◽  
Nude Mice ◽  
Caspase 3 ◽  
Glycogen Synthase ◽  
Inflammatory Factors ◽  
Toll Like Receptor ◽  
Caspase 9 ◽  
Serine Threonine Kinase ◽  
Tnf Α ◽  
Toll Like Receptor 2

Abstract Background β-arrestin-2(Arr2) functions as an anti-apoptotic factor and affects cell proliferation, but its downstream molecular pathway in endometrial carcinoma (EC) is still unclear. This study aimed to investigate the effects of the stable overexpression of Arr2 on the proliferation and apoptosis of human EC heterotransplants and the expression of associated molecules, including Toll-like receptor 2(TLR2), serine-threonine kinase Akt (Akt), glycogen synthase kinase-3β(GSK3β) and some typical inflammatory cytokines such as NF-κB p56, TNF-α and IL-6 & IL-8. Methods Human EC cell line Ishikawa, stably transfected with Arr2 full-length plasmid, was injected subcutaneously into nude mice. They were treated with 0, 10, 20 mg/kg paclitaxel and the volume and weight of the tumor tissue were measured and calculated. The necrotic index were assessed by H&E staining and microscopic observation. The levels of caspase-3, caspase-9, TLR2, NF-κB p56, Akt, GSK3β were measured by western blot, and the levels of TNF-α, IL-6, IL-8 were measured by real-time PCR. Results We found that Arr2 overexpression promoted the growth of human EC heterotransplants. Arr2 attenuated the promotion of caspase-3 and caspase-9 by paclitaxel and mediated the increase of TLR2 and several inflammatory cytokines. The levels of Akt and GSK3β were not affected. Conclusion Arr2 overexpression was associated with the increase of TLR2 and several inflammatory factors, meanwhile inhibited paclitaxel-induced anti-tumor effect on human EC heterotransplants.

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