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https://www.readbyqxmd.com/read/28734982/isolation-and-characterization-of-renin-like-aspartic-proteases-from-echis-ocellatus-venom
#1
M C Wilkinson, D J H Nightingale, R A Harrison, S C Wagstaff
Three aspartic proteases (SVAPs) have been isolated from venom of the saw-scaled viper, Echis ocellatus. In confirmation of prior transcriptomic predictions, all three forms match to sequences of either of the two SVAP transcripts (EOC00051 and EOC00123), have a molecular weight of 42 kDa and possess a single N-glycan. The SVAPs act in a renin-like manner, specifically cleaving human and porcine angiotensinogen into angiotensin-1 and possess no general protease activity. Their activity is completely inhibited by the aspartyl protease inhibitor Pepstatin A...
July 19, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28720877/role-of-the-histone-deacetylase-inhibitor-valproic-acid-in-high-fat-diet-induced-hypertension-via-inhibition-of-hdac1-angiotensin-ii-axis
#2
J Choi, S Y Park, T K Kwon, S-I Sohn, K M Park, J I Kim
BACKGROUND: Obesity is known as an epidemic worldwide because of consumption of westernized high-fat diets and one of the major risk factors of hypertension. Histone deacetylases (HDACs) control gene expression by regulating histone/non-histone protein deacetylation. HDAC inhibitors exert anti-cancer and anti-inflammatory effects and play a protective role in cardiovascular diseases. In the present study, we tested the effect of an FDA-approved pan-HDAC inhibitor valproic acid (VPA) on high-fat diet (HFD)-induced hypertension in mice...
July 19, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28716988/blood-pressure-lowering-and-safety-improvements-with-liver-angiotensinogen-inhibition-in-models-of-hypertension-and-kidney-injury
#3
Adam E Mullick, Steve T Yeh, Mark J Graham, Jeffery A Engelhardt, Thazha P Prakash, Rosanne M Crooke
Uncontrolled hypertension is an important contributor to cardiovascular disease. Despite the armamentarium of antihypertensive treatments, there remains a need for novel agents effective in individuals who cannot reach acceptable blood pressure levels. Inhibitors targeting the renin-angiotensin-aldosterone system (RAAS) are widely used but may not optimally inhibit RAAS and demonstrate an acceptable safety profile. Experiments were conducted to characterize a series of AGT (angiotensinogen) antisense oligonucleotides (ASOs) and compare their efficacy and tolerability to traditional RAAS blockade...
July 17, 2017: Hypertension
https://www.readbyqxmd.com/read/28714028/identification-of-potential-target-genes-associated-with-the-pathogenesis-of-osteoarthritis-using-microarray-based-analysis
#4
Meng Li, Liqiang Zhi, Zhi Zhang, Weiguo Bian, Yusheng Qiu
The aim of the present study was to investigate the molecular circuitry of osteoarthritis (OA) and identify more potential target genes for OA treatment. Microarray data of GSE32317 was downloaded from the National Center for Biotechnology Information Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in samples of synovial membrane from patients with early stage of knee OA (OA_Early) and late stage of knee OA (OA_End) that were compared with healthy specimens. Bioinformatics analysis was applied to analyze the significant functions and pathways that were enriched by the common DEGs identified in OA_Early and OA_End samples...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28698595/the-gene-variants-of-maternal-fetal-renin-angiotensin-system-in-preeclampsia-a-hybrid-case-parent-mother-control-study
#5
Heng Zhang, Ying-Xue Li, Wei-Jun Peng, Zhi-Wei Li, Chun-Hua Zhang, Hai-Hong Di, Xian-Ping Shen, Jun-Feng Zhu, Wei-Rong Yan
Preeclampsia (PE) is a common pregnancy-related complication, and polymorphisms in angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and angiotensin II type 1 receptor (AT1R) are believed to contribute to PE development. We implemented a hybrid study to investigate the influence of maternal and fetal ACE I/D, ACE G2350A, AGT M235T, AGT T174M, and AT1R A1166C polymorphisms on PE in Han Chinese women. Polymorphisms were genotyped in 1,488 subjects (256 patients experiencing PE, along with their fetuses and partners, and 360 normotensive controls with their fetuses)...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698269/urinary-matrix-metalloproteinase-7-predicts-severe-aki-and-poor-outcomes-after-cardiac-surgery
#6
Xiaobing Yang, Chunbo Chen, Siyuan Teng, Xiaorui Fu, Yan Zha, Huafeng Liu, Li Wang, Jianwei Tian, Xiangyan Zhang, Youhua Liu, Jing Nie, Fan Fan Hou
Urinary matrix metalloproteinase-7 (uMMP-7) levels consistently reflect the activity of intrarenal Wnt/β-catenin, which is activated in AKI models. To test the hypothesis that uMMP-7 is a predictor for severe AKI in patients after cardiac surgery, we performed a prospective, multicenter, two-stage cohort study in 721 patients undergoing cardiac surgery. In stage 1, we enrolled 323 children from three academic medical centers. In stage 2, we enrolled 398 adults at six centers. We analyzed levels of uMMP-7 and other injury biomarkers during the perioperative period...
July 11, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28695400/role-of-collecting-duct-renin-in-the-pathogenesis-of-hypertension
#7
REVIEW
Alexis A Gonzalez, Lucienne S Lara, Minolfa C Prieto
The presence of renin production by the principal cells of the collecting duct has opened new perspectives for the regulation of intrarenal angiotensin II (Ang II). Angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) are present in the tubular fluid coming from the proximal tubule and collecting duct. All the components needed for Ang II formation are present along the nephron, and much is known about the mechanisms regulating renin in juxtaglomerular cells (JG); however, those in the collecting duct remain unclear...
August 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/28672944/effective-prediction-of-preeclampsia-by-measuring-serum-angiotensin-ii-urinary-angiotensinogen-and-urinary-transforming-growth-factor-%C3%AE-1
#8
Lihong Zhang, Yunjiao Zhou, Qing Wu, Weifeng Fan, Jun Ye, Yaping Chen, Yun Wu, Jianying Niu, Yong Gu
The aim of the current study was to analyze serum angiotensin II (Ang II), urinary angiotensinogen (AGT) and urinary transforming growth factor β1 (TGFβ1) levels in relation to the clinical manifestation of preeclampsia, and to explore the effects of circulating and renal renin angiotensin system (RAS) in preeclampsia patients. An enzyme-linked immunosorbent assay was used to evaluate serum Ang II, urinary AGT and urinary TGFβ1 in preeclampsia, pregnancy-induced hypertension and normotensive pregnancy patients...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28659284/renal-vascular-and-glomerular-pathologies-associated-with-spontaneous-hypertension-in-the-nonhuman-primate-chlorocebus-aethiops-sabaeus
#9
Megan K Rhoads, Slavina B Goleva, William H Beierwaltes, Jeffrey L Osborn
Hypertension is a complex disease affecting 78 million adults in the United States. The etiology of essential hypertension is unknown and current experimental models do not recapitulate all behavioral and physiological characteristics of the pathology. Researchers should assess the translational capacity of these models and look to other animal models for the discovery of new therapies. Chlorocebus aethiops sabaeus, the African Green Monkey (AGM), is a nonhuman primate that develops spontaneous hypertension and is a novel translational model for the study of hypertension and associated diseases...
June 28, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28641212/association-of-gene-polymorphisms-of-four-components-of-renin-angiotensin-aldosterone-system-and-preeclampsia-in-south-african-black-women
#10
M Aung, T Konoshita, J Moodley, P Gathiram
OBJECTIVE: To investigate the association of the gene polymorphisms of: angiotensinogen (AGT), renin (REN), angiotensin II receptor 1 (AT1R) and angiotensin II receptor 2 (AT2R), in the pathogenesis of PE in South African Black women. METHODOLOGY (STUDY DESIGN): 603 pregnant women; 246 normotensive and 357 with PE (early-onset=187, late-onset=170), were recruited. Each study group was subdivided into HIV infected and uninfected groups. The distribution and frequencies of gene polymorphisms of AGT (M235T), REN (C-5312T), AT1R (A1166C) and AT2R (C3123A) were determined in purified DNA by Real Time Polymerase Chain Reaction...
May 18, 2017: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/28629525/erythropoietin-regulation-by-angiotensin-ii
#11
Yong-Chul Kim, Ognoon Mungunsukh, Regina M Day
The renin-angiotensin system (RAS) is a key regulator of blood pressure and blood volume homeostasis. The RAS is primarily comprised of the precursor protein angiotensinogen and the two proteases, renin and angiotensin-converting enzyme (ACE). Angiotensin I (Ang I) is derived from angiotensinogen by renin, but appears to have no biological activity. In contrast, angiotensin II (Ang II) that has a variety of biological functions in the cells is converted from Ang I through removal of two-C-terminal residues by ACE...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28619367/the-vasoprotective-axes-of-the-renin-angiotensin-system-physiological-relevance-and-therapeutic-implications-in-cardiovascular-hypertensive-and-kidney-diseases
#12
REVIEW
Xiao C Li, Jianfeng Zhang, Jia L Zhuo
The renin-angiotensin system (RAS) is undisputedly one of the most prominent endocrine (tissue-to-tissue), paracrine (cell-to-cell) and intracrine (intracellular/nuclear) vasoactive systems in the physiological regulation of neural, cardiovascular, blood pressure, and kidney function. The importance of the RAS in the development and pathogenesis of cardiovascular, hypertensive and kidney diseases has now been firmly established in clinical trials and practice using renin inhibitors, angiotensin-converting enzyme (ACE) inhibitors, type 1 (AT1) angiotensin II (ANG II) receptor blockers (ARBs), or aldosterone receptor antagonists as major therapeutic drugs...
June 12, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28596160/effects-of-sodium-glucose-cotransporter-2-inhibitors-on-urinary-excretion-of-intact-and-total-angiotensinogen-in-patients-with-type-2-diabetes
#13
Takuo Yoshimoto, Takayuki Furuki, Hiroyuki Kobori, Masaaki Miyakawa, Hitomi Imachi, Koji Murao, Akira Nishiyama
We conducted a descriptive case study to examine the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on urinary angiotensinogen excretion, which represents the function of the intrarenal renin-angiotensin system, in patients with type 2 diabetes. An SGLT2 inhibitor (canagliflozin 100 mg/day, ipragliflozin 25 mg/day, dapagliflozin 5 mg/day, luseogliflozin 2.5 mg/day or tofogliflozin 20 mg/day) was administered for 1 month (n=9). ELISA kits were used to measure both urinary intact and total angiotensinogen levels...
June 8, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28576855/sodium-balance-circadian-bp-rhythm-heart-rate-variability-and-intrarenal-renin-angiotensin-aldosterone-and-dopaminergic-systems-in-acute-phase-of-arb-therapy
#14
Yukako Isobe-Sasaki, Michio Fukuda, Yoshiaki Ogiyama, Ryo Sato, Toshiyuki Miura, Daisuke Fuwa, Masashi Mizuno, Tetsuhei Matsuoka, Hiroko Shibata, Hiroyuki Ito, Minamo Ono, Sumiko Abe-Dohmae, Ken Kiyono, Yoshiharu Yamamoto, Hiroyuki Kobori, Makoto Michikawa, Junichiro Hayano, Nobuyuki Ohte
We have revealed that even in humans, activated intrarenal renin-angiotensin-aldosterone system (RAAS) enhances tubular sodium reabsorption to facilitate salt sensitivity and nondipper rhythm of blood pressure (BP), and that angiotensin receptor blocker (ARB) could increase daytime urinary sodium excretion rate (UNaV) to produce lower sodium balance and restore nondipper rhythm. However, the sympathetic nervous system and intrarenal dopaminergic system can also contribute to renal sodium handling. A total of 20 patients with chronic kidney disease (61 ± 15 years) underwent 24-h ambulatory BP monitoring before and during two-day treatment with ARB, azilsartan...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28572913/hdac9-is-an-epigenetic-repressor-of-kidney-angiotensinogen-establishing-a-sex-difference
#15
Camille T Bourgeois, Ryousuke Satou, Minolfa C Prieto
BACKGROUND: Sexual difference has been shown in the pathogenesis of chronic kidney disease induced by hypertension. Females are protected from hypertension and related end-organ damage. Augmentation of renal proximal tubular angiotensinogen (AGT) expression can promote intrarenal angiotensin formation and the development of associated hypertension and kidney injury. Female rodents exhibit lower intrarenal AGT levels than males under normal conditions, suggesting that the suppressed intrarenal AGT production by programmed mechanisms in females may provide protection from these diseases...
2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28571891/renin-angiotensin-aldosterone-inhibition-in-the-treatment-of-cardiovascular-disease
#16
REVIEW
Carlos M Ferrario, Adam E Mullick
A collective century of discoveries establishes the importance of the renin angiotensin aldosterone system in maintaining blood pressure, fluid volume and electrolyte homeostasis via autocrine, paracrine and endocrine signaling. While research continues to yield new functions of angiotensin II and angiotensin-(1-7), the gap between basic research and clinical application of these new findings is widening. As data accumulates on the efficacy of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers as drugs of fundamental importance in the treatment of cardiovascular and renal disorders, it is becoming apparent that the achieved clinical benefits is suboptimal and surprisingly no different than what can be achieved with other therapeutic interventions...
May 29, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28534088/the-ppar-gamma-binding-sequence-pal3-is-necessary-for-basal-but-dispensable-for-high-fat-diet-regulated-human-renin-expression-in-the-kidney
#17
Peter Lachmann, Jenny Selbmann, Linda Hickmann, Bernd Hohenstein, Christian Hugo, Vladimir T Todorov
We reported earlier that PPAR-gamma regulates renin transcription through a human-specific atypical binding sequence termed hRen-Pal3. Here we developed a mouse model to investigate the functional relevance of the hRen-Pal3 sequence in vivo since it might be responsible for the increased renin production in obesity and thus for the development of accompanying arterial hypertension. We used bacterial artificial chromosome construct and co-placement strategy to generate two transgenic mouse lines expressing the human renin gene from identical genomic locus without affecting the intrinsic mouse renin expression...
May 22, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28515914/analysis-of-the-function-of-microrna-375-in-humans-using-bioinformatics
#18
Xiaohua Chen, Baoxia Li, Rongcheng Luo, Sina Cai, Cao Zhang, Xiaolong Cao
MicroRNA-375 (miR-375) is expressed at low levels in many types of solid tumor, particularly in gastrointestinal tumors. It is considered to be important in the development of cancer and certain diseases. Thus, more detailed knowledge is required on the particular functions of miR-375. miRs function by regulating target genes. Therefore, in the current study, miRWalk (which includes the data from 10 prediction software programs) was used to predict the target genes of miR-375. The genes, which were co-predicted using five different software programs were further analyzed using Database for Annotation, Visualization and Integrated Discovery online software [including gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis]...
May 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28509726/sodium-butyrate-suppresses-angiotensin-ii-induced-hypertension-by-inhibition-of-renal-pro-renin-receptor-and-intrarenal-renin-angiotensin-system
#19
Lei Wang, Qing Zhu, Aihua Lu, Xiaofen Liu, Linlin Zhang, Chuanming Xu, Xiyang Liu, Haobo Li, Tianxin Yang
OBJECTIVES: Butyrate, a short-chain fatty acid, is the end product of the fermentation of complex carbohydrates by the gut microbiota. Recently, sodium butyrate (NaBu) has been found to play a protective role in a number of chronic diseases. However, it is still unclear whether NaBu has a therapeutic potential in hypertension. The present study was aimed to investigate the role of NaBu in angiotensin II (Ang II)-induced hypertension and to further explore the underlying mechanism. METHODS: Ang II was infused into uninephrectomized Sprague-Dawley rats with or without intramedullary infusion of NaBu for 14 days...
May 13, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28506960/familial-analysis-of-epistatic-and-sex-dependent-association-of-genes-of-the-renin-angiotensin-aldosterone-system-and-blood-pressure
#20
Katrina J Scurrah, Angela Lamantia, Justine A Ellis, Stephen B Harrap
BACKGROUND: Renin-angiotensin-aldosterone system genes have been inconsistently associated with blood pressure, possibly because of unrecognized influences of sex-dependent genetic effects or gene-gene interactions (epistasis). METHODS AND RESULTS: We tested association of systolic blood pressure with single-nucleotide polymorphisms (SNPs) at renin (REN), angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AGTR1), and aldosterone synthase (CYP11B2), including sex-SNP or SNP-SNP interactions...
June 2017: Circulation. Cardiovascular Genetics
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