-
Animals : An Open Access Journal From... Jun 2024The skin of bony fish is the first physical barrier and is responsible for maintaining the integrity of the fish. Lesions make the skin vulnerable to potential infection...
The skin of bony fish is the first physical barrier and is responsible for maintaining the integrity of the fish. Lesions make the skin vulnerable to potential infection by pathogens present in the aquatic environment. In this way, wound repair has barely been studied in gilthead sea bream. Thus, this study investigated the modulation of peripheral neuro-endocrine and tissue repair markers at the transcriptional level in the skin of teleost fish subjected to mechanical damage above or below the lateral line (dorsal and ventral lesions, respectively). Samples were evaluated using RT-qPCR at 2-, 4-, and 20-days post-injury. Fish with a ventral lesion presented a trend of progressive increase in the expressions of (), (), (), (), (), (), and (less pronounced) (). By contrast, fish with a dorsal lesion registered no significant increase or biological trend for the genes evaluated at the different sampling times. Collectively, the results show a rapid and more robust response of neuro-endocrine and tissue repair markers in the injuries below than above the lateral line, which could be attributable to their proximity to vital organs.
PubMed: 38929434
DOI: 10.3390/ani14121815 -
Therapeutic Apheresis and Dialysis :... Jun 2024This study aims to examine the relationship between fluid overload, Vascular Endothelial Growth Factor C (VEGF-C), plasma Angiotensinogen (pAGT), and echocardiography...
INTRODUCTION
This study aims to examine the relationship between fluid overload, Vascular Endothelial Growth Factor C (VEGF-C), plasma Angiotensinogen (pAGT), and echocardiography findings in hemodialysis patients.
METHODS
This was a single-center, cross-sectional study. Patients were divided into two groups according to mid-week inter-dialytic weight gain (mIDWG): (1) mIDWG ≤3% and (2) mIDW >3%.
RESULTS
A total of 55 patients were enrolled in this study. While the mean pAGT and left ventricular mass index were significantly higher in patients with mIDWG >3% compared to patients with mIDWG ≤3%, VEGF-C was similar between groups. pAGT ≥76.8 mcg/L, VEGF-C ≤175.5 pg/ML, and pAGT /VEGF-C ≥0.45 were significant cut-offs for the prediction of left ventricular hypertrophy(LVH). Univariate logistic regression analysis revealed that these cut-off values were significantly associated with LVH.
CONCLUSION
Renin-angiotensin-aldosterone system activation may persist in hemodialysis patients with excessive IDWG. Additionally, pAGT and VEGF-C could be risk factors for the development of LVH.
PubMed: 38894556
DOI: 10.1111/1744-9987.14178 -
Food Research International (Ottawa,... Aug 2024Edible insects are recognized as promising food sources due to their nutritional composition. Some species, such as Gryllus assimilis, contain proteins, lipids, and...
Edible insects are recognized as promising food sources due to their nutritional composition. Some species, such as Gryllus assimilis, contain proteins, lipids, and carbohydrates of high biological value, which regulate several metabolic functions, including the Renin-Angiotensin System (RAS). In this context, the present study aimed to assess the effects of dietary supplementation with whole Gryllus assimilis powder on the metabolism of malnourished mice. Thirty-two male Swiss mice were used and divided into four treatment groups. The groups were identified as (AIN93-M); AIN93-M + Gryllus assimilis diet (AIN93-M + GA); AIN93-M + Renutrition diet (AIN93-M + REN) and AIN93-M + Renutrition diet + Gryllus assimilis (AIN93-M + REN + GA). The results showed that whole Gryllus assimilis powder inclusion promotes recovery from protein-energy malnutrition, reduces adiposity, and improves glucose tolerance and insulin sensitivity. It also reduces total cholesterol, triglycerides, VLDL, and adipocyte area. We also observed a significant increase in the expression of RAS-related genes, such as ACE2 and MasR, followed by a reduction in Angiotensinogen and ACE. The main findings of the present study suggest the use of black cricket as a viable strategy for the prevention and treatment of protein-energy malnutrition, as well as the reduction of adiposity, and improvement of lipid and glycemic parameters, with antihypertensive potential.
Topics: Animals; Renin-Angiotensin System; Male; Dietary Supplements; Mice; Gryllidae; Protein-Energy Malnutrition; Adipose Tissue; Adiposity; Insulin Resistance
PubMed: 38876598
DOI: 10.1016/j.foodres.2024.114570 -
Chronic Diseases and Translational... Jun 2024Hypertension (HTN) involves genetic variability in the renin-angiotensin system and influences antihypertensive response. We previously reported that angiotensinogen ()...
BACKGROUND
Hypertension (HTN) involves genetic variability in the renin-angiotensin system and influences antihypertensive response. We previously reported that angiotensinogen () messenger RNA (mRNA) is endogenously bound by miR-122-5p and rs699 A > G decreases reporter mRNA in the microRNA functional-assay PASSPORT-seq. The promoter variant rs5051 C > T is in linkage disequilibrium (LD) with rs699 A > G and increases transcription. The independent effect of these variants is understudied due to their LD therefore we aimed to test the hypothesis that increased by rs5051 C > T counterbalances decreased by rs699 A > G, and when these variants occur independently, it translates to HTN-related phenotypes.
METHODS
We used in silico, in vitro, in vivo, and retrospective models to test this hypothesis.
RESULTS
In silico, rs699 A > G is predicted to increase miR-122-5p binding affinity by 3%. Mir-eCLIP results show rs699 is 40-45 nucleotides from the strongest microRNA-binding site in the mRNA. Unexpectedly, rs699 A > G increases mRNA in an -plasmid-cDNA HepG2 expression model. Genotype-Tissue Expression (GTEx) and UK Biobank analyses demonstrate liver expression and HTN phenotypes are not different when rs699 A > G occurs independently from rs5051 C > T. However, GTEx and the in vitro experiments suggest rs699 A > G confers cell-type-specific effects on mRNA abundance, and suggest paracrine renal renin-angiotensin-system perturbations could mediate the rs699 A > G associations with HTN.
CONCLUSIONS
We found that rs5051 C > T and rs699 A > G significantly associate with systolic blood pressure in Black participants in the UK Biobank, demonstrating a fourfold larger effect than in White participants. Further studies are warranted to determine if altered antihypertensive response in Black individuals might be due to rs5051 C > T or rs699 A > G. Studies like this will help clinicians move beyond the use of race as a surrogate for genotype.
PubMed: 38872760
DOI: 10.1002/cdt3.103 -
Medicina Clinica Jun 2024Even though a large number of antihypertensive drugs are suitable for hypertension treatment, some new therapeutic targets are recently under development. Most are... (Review)
Review
Even though a large number of antihypertensive drugs are suitable for hypertension treatment, some new therapeutic targets are recently under development. Most are focused in the treatment of resistant hypertension, added to the drugs currently available for treating such condition. Others have specific particularities in their duration of action, which allows their use once per month or every six months and could become alternatives to the current antihypertensive treatment. Most interesting therapeutic targets are the renin-angiotensin-aldosterone system, through interference with the RNA of the angiotensinogen, the inhibition of brain aminopeptidase III, the inhibition of aldosterone synthase, and new non-steroidal aldosterone receptor antagonists. In addition, dual endothelin receptor antagonists or agonists of the NPR1 receptor, the main effector of natriuretic peptides are other new interesting therapeutic possibilities. In this paper, we review clinical data on the development of the most interesting molecules acting through these new therapeutic targets.
PubMed: 38849267
DOI: 10.1016/j.medcli.2024.03.028 -
Discovery Medicine May 2024Cardiovascular disease stands as the leading cause of death globally, with hypertension emerging as an independent risk factor for its development. The worldwide... (Review)
Review
Cardiovascular disease stands as the leading cause of death globally, with hypertension emerging as an independent risk factor for its development. The worldwide prevalence of hypertension hovers around 30%, encompassing a staggering 1.2 billion patients, and continues to escalate annually. Medication plays a pivotal role in managing hypertension, not only effectively regulating blood pressure (BP) but also substantially mitigating the occurrence of cardiovascular and cerebrovascular diseases. This review comprehensively outlines the categories, mechanisms, clinical applications, and drawbacks of conventional antihypertensive drugs. It delves into the five primary pharmacological classifications, namely β-receptor blockers, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and diuretics. The emphasis is placed on elucidating the mechanisms, advantages, and research progress of novel antihypertensive drugs targeting emerging areas. These include mineralocorticoid receptor antagonists (MRAs), atrial natriuretic peptides (ANPs), neutral endopeptidase inhibitors (NEPIs), sodium-dependent glucose transporter 2 inhibitors (SGLT-2Is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), endothelin receptor antagonists (ERAs), soluble guanylate cyclase (sGC) agonists, brain aminopeptidase A inhibitors (APAIs), and small interfering ribonucleic acids (siRNAs) targeting hepatic angiotensinogen. Compared to conventional antihypertensive drugs, these novel alternatives exhibit favorable antihypertensive effects with minimal adverse reactions. This review serves as a valuable reference for future research and the clinical application of antihypertensive drugs.
Topics: Humans; Antihypertensive Agents; Hypertension; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Calcium Channel Blockers; Animals; Adrenergic beta-Antagonists; Diuretics; Mineralocorticoid Receptor Antagonists
PubMed: 38798249
DOI: 10.24976/Discov.Med.202436184.83 -
Foods (Basel, Switzerland) May 2024In this study, we investigated the anti-hypertensive properties of mulberry products by modulating the renin-angiotensin system (RAS). Comparative analysis showed that...
In this study, we investigated the anti-hypertensive properties of mulberry products by modulating the renin-angiotensin system (RAS). Comparative analysis showed that the ethyl acetate fractions, particularly from the Cheongil and Daeshim cultivars, contained the highest levels of polyphenols and flavonoids, with concentrations reaching 110 mg gallic acid equivalent (GE)/g and 471 mg catechin equivalent (CE)/g of extract, respectively. The ethyl acetate fraction showed superior angiotensin-converting enzyme (ACE) inhibitory activity, mainly because of the presence of the prenylated flavonoids kuwanon G and H. UPLC/Q-TOF-MS analysis identified kuwanon G and H as the primary active components, which significantly contributed to the pharmacological efficacy of the extract. In vivo testing of mice fed a high-salt diet showed that the ethyl acetate fraction substantially reduced the heart weight and lowered the serum renin and angiotensinogen levels by 34% and 25%, respectively, highlighting its potential to modulate the RAS. These results suggested that the ethyl acetate fraction of mulberry root bark is a promising candidate for the development of natural ACE inhibitors. This finding has significant implications for the management of hypertension through RAS regulation and the promotion of cardiovascular health in the functional food industry.
PubMed: 38790847
DOI: 10.3390/foods13101547 -
Hypertension (Dallas, Tex. : 1979) May 2024Angiotensin-(1-12), measured by a self-developed, polyclonal antibody-based radioimmunoassay, has been suggested to act as an alternative precursor of angiotensin II. A...
BACKGROUND
Angiotensin-(1-12), measured by a self-developed, polyclonal antibody-based radioimmunoassay, has been suggested to act as an alternative precursor of angiotensin II. A more reliable detection method would be liquid chromatography-tandem mass spectrometry.
METHODS
We set up the quantification of human and murine angiotensin-(1-12) by liquid chromatography-tandem mass spectrometry and then used this method to measure angiotensin-(1-12) in human and mouse blood samples, as well as in mouse brain and kidney. We also verified ex vivo angiotensin-(1-12) generation and metabolism in human blood samples incubated at 37 °C.
RESULTS
Stabilization of blood in guanidine hydrochloride was chosen for sample collection since this allowed full recovery of spiked angiotensin-(1-12). Angiotensin-(1-12) was undetectable in human blood samples when incubating nonstabilized plasma at 37 °C, while angiotensin-(1-12) added to nonstabilized human plasma disappeared within 10 minutes. Stabilized human blood samples contained angiotensin II, while angiotensin-(1-12) was undetectable. Blood, hearts, and kidneys, but not brains, of wild-type mice and rats contained detectable levels of angiotensin II, while angiotensin-(1-12) was undetectable. In renin knockout mice, all angiotensins, including angiotensin-(1-12), were undetectable at all sites, despite a 50% rise in angiotensinogen. Angiotensin-(1-12) metabolism in human blood plasma was not affected by renin inhibition. Yet, blockade of angiotensin-converting enzyme and aminopeptidase A, but not of chymase, neutral endopeptidase, or prolyl oligopeptidase, prolonged the half-life of angiotensin-(1-12), and angiotensin-converting enzyme inhibition prevented the formation of angiotensin II.
CONCLUSIONS
We were unable to detect intact angiotensin-(1-12) in humans or mice, either in blood or tissue, suggesting that this metabolite is an unlikely source of endogenous angiotensins.
PubMed: 38716648
DOI: 10.1161/HYPERTENSIONAHA.124.22856 -
The European Journal of Neuroscience May 2024Gastrodin, an anti-inflammatory herbal agent, is known to suppress microglia activation. Here, we investigated whether it would exert a similar effect in reactive...
Gastrodin, an anti-inflammatory herbal agent, is known to suppress microglia activation. Here, we investigated whether it would exert a similar effect in reactive astrocytes and whether it might act through the renin-angiotensin system (RAS) and sirtuin 3 (SIRT3). Angiotensinogen (ATO), angiotensin-converting enzyme (ACE), angiotensin II type 1 (AT) and type 2 (AT) receptor and SIRT3 expression was detected in TNC-1 astrocytes treated with BV-2 microglia conditioned medium (CM) with or without gastrodin and lipopolysaccharide (LPS) pre-treatment by RT-PCR, immunofluorescence and western blotting analysis. Expression of C3 (A1 astrocyte marker), S100A10 (A2 astrocyte marker), proinflammatory cytokines and neurotrophic factors was then evaluated. The results showed a significant increase of ATO, ACE, AT, SIRT3, C3, proinflammatory cytokines and neurotrophic factors expression in TNC-1 astrocytes incubated in CM + LPS when compared with cells incubated in the CM, but AT and S100A10 expression was reduced. TNC-1 astrocytes responded vigorously to BV-2 CM treated with gastrodin + LPS as compared with the control. This was evident by the decreased expression of the abovementioned protein markers, except for AT and S100A10. Interestingly, SIRT3, IGF-1 and BDNF expression was enhanced, suggesting that gastrodin inhibited the expression of RAS and proinflammatory mediators but promoted the expression of neurotrophic factors. And gastrodin regulated the phenotypic changes of astrocytes through AT. Additionally, azilsartan (a specific inhibitor of AT) inhibited the expression of C3 and S100A10, which remained unaffected in gastrodin and azilsartan combination treatment. These findings provide evidence that gastrodin may have a therapeutic effect via regulating RAS-SIRT3.
PubMed: 38711280
DOI: 10.1111/ejn.16371 -
Diabetes, Metabolic Syndrome and... 2024Hypertension is a leading cause of cardiovascular-related morbidity and mortality worldwide, with a prevalence increasing at an alarming rate in both middle- and...
PURPOSE
Hypertension is a leading cause of cardiovascular-related morbidity and mortality worldwide, with a prevalence increasing at an alarming rate in both middle- and low-income countries. Various environmental and genetic factors have been attributed to play a significant role in the increasing prevalence of hypertension. Single nucleotide polymorphisms (SNPs) in the angiotensinogen () gene are reported to have a significant association with hypertension; however, there are limited studies done on South African populations. Therefore, this case-control study aimed to investigate the association between SNPs (rs2004776, rs3789678, rs5051 and rs7079) with hypertension in a study population of isiXhosa-speaking participants from the Eastern Cape Province in South Africa.
MATERIALS AND METHODS
The SNPs were genotyped in 250 hypertensive cases and 237 normotensive controls, using TaqMan genotyping assays.
RESULTS
For the SNP rs2004776, the frequency of CC genotype (18.4%) and C allele (44%) in hypertensive cases showed no significant differences (p = 0.52, χ2 = 1.32), when compared to the normotensive control group (CC: 19.8% and C allele: 43%). Similar results were obtained for the genotypic and allelic frequencies between hypertensive cases and normotensive controls for rs3789678 (p = 0.88, χ2=0.26) and rs5051 (p = 0.57, χ2=1.12), and rs7079 (p = 0.33, χ2=2.23). These findings demonstrate that there were no significant associations between the SNPs rs2004776, rs3789678, rs7079, rs5051 with hypertension in our study population.
CONCLUSION
These findings suggest that gene polymorphisms are not associated with the development of hypertension in the studied population. The present study represents the first genetic report to investigate the gene polymorphisms with hypertension in an isiXhosa-speaking South African population.
PubMed: 38706806
DOI: 10.2147/DMSO.S452272