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Journal of Clinical Laboratory Analysis May 2024The interference can be a significant source of laboratory errors with the potential to cause immunoassay results to drift. Therefore, we evaluated the interference in...
BACKGROUND
The interference can be a significant source of laboratory errors with the potential to cause immunoassay results to drift. Therefore, we evaluated the interference in various endogenous and exogenous substances on immunoassay for angiotensin I (Ang I), angiotensin II (Ang II), aldosterone, and renin in vitro.
METHODS
Ten endogenous and eight exogenous substances were evaluated at supraphysiologic or supratherapeutic plasma levels using the screening study to identify potential interfering substances. Subsequently, potential interfering substances were further tested within maximum pathological or therapeutic plasma concentration ranges using the dose-response study to determine whether the interference has a significant bias. According to preset acceptance criteria, the interference in potential interfering substances for Ang I, Ang II, and renin and aldosterone assays was determined.
RESULTS
Six potential interfering substances for Ang I immunoassays were identified, namely valsartan, nifedipine, spironolactone, cholesterol, hemoglobin, and triglyceride. Meanwhile, ethanol, nifedipine, spironolactone, heparin sodium, warfarin, hemoglobin, uric acid, cholesterol, and triglyceride appeared to have potential interference in the Ang II assay. Three identified as possible interferents for aldosterone immunoassays were glucose, valsartan, and spironolactone. Moreover, warfarin, valsartan, spironolactone, uric acid, cholesterol, bilirubin unconjugated, triglyceride, and hemoglobin were potential interfering substances for renin immunoassays. However, only spironolactone of these potential interfering substances exceeded preset mean bias limits (less than ±10.0%) in aldosterone immunoassays.
CONCLUSION
Exogenous spironolactone caused clinically significant interference in aldosterone immunoassays. Moreover, the interference in other substances was acceptable in Ang I, Ang II, and renin and aldosterone immunoassays.
Topics: Humans; Angiotensin II; Aldosterone; Renin; Immunoassay; Angiotensin I; Luminescent Measurements
PubMed: 38822626
DOI: 10.1002/jcla.25045 -
Current Problems in Cardiology Aug 2023Cardiovascular disease is the greatest health care burden and one of the most common causes of death worldwide. Less is known about the genetic factors that are... (Review)
Review
Cardiovascular disease is the greatest health care burden and one of the most common causes of death worldwide. Less is known about the genetic factors that are responsible for predisposition to cardiovascular disease thus; the molecular and genetic mechanisms underlying cardiovascular diseases remain obscure. One important regulator of blood pressure homeostasis is the renin-angiotensin system. The protease renin cleaves angiotensinogen into the inactive decameric peptide angiotensin I (Ang I). Angiotensin-converting enzyme (ACE) catalyzes the cleavage of the Ang I into the active octomer angiotensin II (Ang II). In humans, can ACE polymorphism has been associated with determinants of renal and cardiovascular function and pharmacological inhibition of ACE and Ang II receptors are effective in lowering blood pressure and preventing kidney disease. In addition, inhibition of ACE and Ang II receptors has beneficial effects in heart failure. A homologue of ACE, termed ACE2, has been identified; it is predominantly expressed in the vascular endothelial cells of the kidney and heart. Unlike ACE, ACE2 functions as a carboxypeptidase, cleaving a single residue from AngI, generating Ang1-9, and a single residue from AngII to generate Ang1-7. Nevertheless, the in vivo role of ACE2 in the cardiovascular system and the renin-angiotensin system is not known.
Topics: Humans; Cardiovascular Diseases; Angiotensin-Converting Enzyme 2; Endothelial Cells; Renin-Angiotensin System; Kidney
PubMed: 35245599
DOI: 10.1016/j.cpcardiol.2022.101162 -
Genes Oct 2023The Mediterranean diet (MedD) has been shown to have beneficial effects on health, well-being, and mental status. It potentially modulates gene expressions linked to...
The Mediterranean diet (MedD) has been shown to have beneficial effects on health, well-being, and mental status. It potentially modulates gene expressions linked to oxidative stress, contributing to its beneficial effects on overall health. The aim of this study was to assess the effects of MedD treatment in healthy human volunteers on the expression of ten genes related to oxidative stress and inflammation in women and men. Of 30 enrolled subjects, 17 were eligible, 10 women and 7 men. All of them received the same MedD treatment. Before and after 8 weeks of MedD treatment, an evaluation of body composition, blood tests, and anthropometric and clinical parameters was performed. Furthermore, 10 genes were amplified and analyzed. The study showed significant differences between females and males in body composition and biochemical parameters before and after MedD treatment. Significant differences between females and males in Resistance Force ( < 0.009) and Diastolic Blood Pressure ( < 0.04) before MedD treatment, and in High-Density Lipoprotein ( < 0.02) after MedD treatment, were observed. Moreover, a significant upregulation of and in females has been shown. Sex differences impact MedD treatment response, and influence the genetic expression of genes related to oxidative stress; our findings may help to personalize diet therapy and contribute to overall health and well-being.
Topics: Humans; Male; Female; Diet, Mediterranean; Pilot Projects; Nutrigenomics; Sex Characteristics; Oxidative Stress
PubMed: 38002923
DOI: 10.3390/genes14111980 -
Critical Care (London, England) Apr 2024Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARB) medications are widely prescribed. We sought to assess how pre-admission use of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARB) medications are widely prescribed. We sought to assess how pre-admission use of these medications might impact the response to angiotensin-II treatment during vasodilatory shock.
METHODS
In a post-hoc subgroup analysis of the randomized, placebo-controlled, Angiotensin Therapy for High Output Shock (ATHOS-3) trial, we compared patients with chronic angiotensin-converting enzyme inhibitor (ACEi) use, and patients with angiotensin receptor blocker (ARB) use, to patients without exposure to either ACEi or ARB. The primary outcome was mean arterial pressure after 1-h of treatment. Additional clinical outcomes included mean arterial pressure and norepinephrine equivalent dose requirements over time, and study-drug dose over time. Biological outcomes included baseline RAS biomarkers (renin, angiotensin-I, angiotensin-II, and angiotensin-I/angiotensin-II ratio), and the change in renin from 0 to 3 h.
RESULTS
We included n = 321 patients, of whom, 270 were ACEi and ARB-unexposed, 29 were ACEi-exposed and 22 ARB-exposed. In ACEi/ARB-unexposed patients, angiotensin-treated patients, compared to placebo, had higher hour-1 mean arterial pressure (9.1 mmHg [95% CI 7.6-10.1], p < 0.0001), lower norepinephrine equivalent dose over 48-h (p = 0.0037), and lower study-drug dose over 48-h (p < 0.0001). ACEi-exposed patients treated with angiotensin-II showed similarly higher hour-1 mean arterial pressure compared to ACEi/ARB-unexposed (difference in treatment-effect: - 2.2 mmHg [95% CI - 7.0-2.6], p = 0.38), but a greater reduction in norepinephrine equivalent dose (p = 0.0031) and study-drug dose (p < 0.0001) over 48-h. In contrast, ARB-exposed patients showed an attenuated effect of angiotensin-II on hour-1 mean arterial pressure versus ACEi/ARB-unexposed (difference in treatment-effect: - 6.0 mmHg [95% CI - 11.5 to - 0.6], p = 0.0299), norepinephrine equivalent dose (p < 0.0001), and study-drug dose (p = 0.0008). Baseline renin levels and angiotensin-I/angiotensin-II ratios were highest in ACEi-exposed patients. Finally, angiotensin-II treatment reduced hour-3 renin in ACEi/ARB-unexposed and ACEi-exposed patients but not in ARB-exposed patients.
CONCLUSIONS
In vasodilatory shock patients, the cardiovascular and biological RAS response to angiotensin-II differed based upon prior exposure to ACEi and ARB medications. ACEi-exposure was associated with increased angiotensin II responsiveness, whereas ARB-exposure was associated with decreased responsiveness. These findings have clinical implications for patient selection and dosage of angiotensin II in vasodilatory shock. Trial Registration ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Angiotensin II; Renin; Angiotensin Receptor Antagonists; Shock; Norepinephrine
PubMed: 38637829
DOI: 10.1186/s13054-024-04910-6 -
Journal of Chemical Information and... Aug 2023Angiotensin-(1-7) is an endogenous peptide known for its vasoprotective, antioxidant, and anti-inflammatory effects, making it a promising therapeutic candidate for...
Angiotensin-(1-7) is an endogenous peptide known for its vasoprotective, antioxidant, and anti-inflammatory effects, making it a promising therapeutic candidate for various clinical conditions. However, the peptide exhibits pH-dependent physical instability in aqueous solutions, and a comprehensive atomistic study elucidating this behavior and its implications is currently lacking. Therefore, we performed all-atom molecular dynamics simulations to investigate the early formation of angiotensin-(1-7) oligomeric aggregates under different conditions: acidic and neutral pH-like conditions, physiological and high ionic strength, and high and low peptide concentrations. Our results are as follows: (1) under acidic pH-like conditions, angiotensin-(1-7) showed minimal clustering, (2) under neutral pH-like conditions, the peptides aggregated into a single cluster, consistent with the reported physical instability, and (3) increasing salt concentration under acidic pH-like conditions resulted in aggregation similar to that observed under neutral pH-like conditions. These results suggest that a combination of salt concentration and pH conditions can modulate angiotensin-(1-7) aggregation. Our protocol (molecular dynamics + cluster analysis + amino acid interaction map analysis) is general and could be applied to other peptides to study interpeptide interaction mechanisms.
Topics: Peptide Fragments; Angiotensin I; Amino Acids; Cluster Analysis; Sodium Chloride
PubMed: 37589289
DOI: 10.1021/acs.jcim.3c00478 -
Frontiers in Oncology 2023Endometrial cancer (EC), the most common adenocarcinoma, represents 90% of uterine cancer in women with an increased incidence of occurrence attributed to age, obesity,... (Review)
Review
Endometrial cancer (EC), the most common adenocarcinoma, represents 90% of uterine cancer in women with an increased incidence of occurrence attributed to age, obesity, hypertension, and hypoestrogenism. Being the most common gynecological malignancy in women, it shows a relation with the activation of different components of the renin-angiotensin system (RAS), which is predominantly involved in maintaining blood pressure, salt, water, and aldosterone secretion, thereby playing a significant role in the etiology of hypertension. The components of the RAS, i.e., ACE-I, ACE-II, AT1R, AT2R, and Pro(renin) receptor, are widely expressed in both glandular and stromal cells of the endometrium, with varying levels throughout the different phases of the menstrual cycle. This causes the endometrial RAS to implicate angiogenesis, neovascularization, and cell proliferation. Thus, dysfunctioning of the endometrial RAS could predispose the growth and spread of EC. Interestingly, the increased expression of AngII, AGTR1, and AGTR2 showed advancement in the stages and progression of EC via the prorenin/ATP6AP2 and AngII/AGTR1 pathway. Therefore, this review corresponds to unraveling the relationship between the progression and development of endometrial cancer with the dysfunction in the expression of various components associated with RAS in maintaining blood pressure.
PubMed: 37869088
DOI: 10.3389/fonc.2023.1235418 -
Journal of Theoretical Biology Sep 2023The renin-angiotensin systems play pivotal role in cardiovascular physiology through its effects on regulating blood pressure and electrolyte homeostasis. Components of...
The renin-angiotensin systems play pivotal role in cardiovascular physiology through its effects on regulating blood pressure and electrolyte homeostasis. Components of circulating RAS (cRAS) that include precursor angiotensinogen, two critical enzymes (renin and angiotensin-converting enzyme, ACE), their bioactive products, angiotensin- I, II together with its receptors (AT1R and AT2R) essentially determine this homeostasis. Most classical studies, however, showed the deleterious role of cRAS in elevating the blood pressure. Contemporary discovery of non-canonical components of the RAS has challenged this classic hypothesis that it can only exert deleterious effects on the cardiovascular systems. Using the classic cRAS model, we have designed in-silico experiments to test the hypothesis that AT2R-mediated feedback effects play pivotal role for maintaining the normal variation of the mean-arterial pressure (MAP).Beside the AT2R-mediation of downstream singling pathways consisting of several non-canonical RAS components, this study first time illustrated AT2R mediated feedback controls over the blood pressure regulation: one that impedes AT1R activity, and the other that downregulates renin. It has been shown that relatively stronger suppression of renin activity significantly contributes in maintaining the normal MAP and that tight AT2R-mediated regulation is relaxed in hyper-and hypotension. This control mechanism is noted to be robustly maintained with the MAP variations through an established linear steady-state relationship among renin, angiotensin I and angiotensin II. This examination suggests that AT2R-mediated downregulation of renin activities potentially counteracts the AT1R-mediated deleterious actions of Ang II. This study, therefore, provides a solid ground for considering different AT2 receptor adaptor protein and direct agonism at AT2R that can cause greater effects along with contemporary approaches of blocking AT1R mediation to attenuate hypertension or other cardiovascular disorders.
Topics: Renin; Feedback; Arterial Pressure; Renin-Angiotensin System; Angiotensin II
PubMed: 37532028
DOI: 10.1016/j.jtbi.2023.111589 -
Cureus Dec 2023The growing research regarding the implementation of angiotensin-converting enzyme-2 inhibitors (ACEi) and angiotensin receptor blockers (ARBs) in the treatment of... (Review)
Review
Clinical Outcomes of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in COVID-19 Patients With Pre-existing Cardiac Comorbidities: A Literature Review.
The growing research regarding the implementation of angiotensin-converting enzyme-2 inhibitors (ACEi) and angiotensin receptor blockers (ARBs) in the treatment of COVID-19 in patients with pre-existing cardiac comorbidities has become a large topic of discussion since the onset of the pandemic. Previous research primarily associates positive outcomes to the use of these drug classes due to their mechanism of action, which involves the downregulation of angiotensin I-converting enzyme 2 (ACE2) in the renin-angiotensin-aldosterone-system (RAAS) pathway, inflammatory mediators, and cytokines. Thus, these medications can convey preventative and protective effects in patients suffering from a SARS-CoV-2 infection. While we explored the studies that supported the positive outcomes of the use of these drugs in the first half of this review, we also expanded on the limitations of these studies in the latter portion. We also further explored the contradictory studies that indicated that using these antihypertensives can paradoxically increase the severity of COVID-19 infection as well. The studies in support of the use of these medications should consider epigenetic variations, ACE2 variants and acknowledge inherent genetic variations in certain ethnic groups as some have a predisposition for a severe COVID-19 infection. Additionally, mortality rates need to be taken into consideration in these studies as they naturally differ throughout the trajectory of the COVID-19 pandemic. While some studies are in support of the use of these antihypertensives despite other studies suggesting otherwise, further research is needed to explore the long-term effects of these antihypertensives and observe whether they are truly beneficial or not in reducing the severity of COVID-19 infections.
PubMed: 38283421
DOI: 10.7759/cureus.51244 -
International Journal of Molecular... Jul 2023Angiotensin I-converting enzyme (ACE) is an important blood pressure regulator. In this study, we aimed to investigate the ACE-inhibitory effects of meroterpenoids...
Angiotensin I-converting enzyme (ACE) is an important blood pressure regulator. In this study, we aimed to investigate the ACE-inhibitory effects of meroterpenoids isolated from the brown alga, , and the molecular mechanisms underlying ACE inhibition. Four fractions of were prepared using hexane, chloroform, ethyl acetate, and water as solvents and analyzed for their potential ACE-inhibitory effects. The chloroform fraction showed the strongest ACE-inhibitory effect, with an IC value of 0.18 mg/mL. Three meroterpenoids, sargachromenol, 7-methyl sargachromenol, and sargaquinoic acid, were isolated from the chloroform fraction. Meroterpenoids isolated from had IC values of 0.44, 0.37, and 0.14 mM. The molecular docking study revealed that the ACE-inhibitory effect of the isolated meroterpenoids was mainly attributed to Zn-ion, hydrogen bonds, pi-anion, and pi-alkyl interactions between the meroterpenoids and ACE. These results suggest that could be a potential raw material for manufacturing antihypertensive nutraceutical ingredients.
Topics: Angiotensin-Converting Enzyme Inhibitors; Molecular Docking Simulation; Sargassum; Peptidyl-Dipeptidase A; Chloroform
PubMed: 37446242
DOI: 10.3390/ijms241311065 -
Food Chemistry Mar 2024This study aimed to screen novel angiotensin I-converting enzyme (ACE) inhibitory peptides from garlic proteins and to explore their underlying antihypertensive...
Two novel angiotensin I-converting enzyme inhibitory peptides from garlic protein: In silico screening, stability, antihypertensive effects in vivo and underlying mechanisms.
This study aimed to screen novel angiotensin I-converting enzyme (ACE) inhibitory peptides from garlic proteins and to explore their underlying antihypertensive mechanisms in vivo. After simulated hydrolysis and in silico screening, two novel peptides (MGR and HDCF) were obtained with the highest ACE inhibitory activity (IC of 4.50 μM and 26.38 μM) and acted as competitive inhibitors. They interacted with key residues in the ACE receptor mainly through hydrogen bonding and exhibited excellent stability against high temperature, extreme pH, and gastrointestinal digestion. In spontaneously hypertensive rats, MGR and HDCF effectively lowered blood pressure after single or continuous treatments. This was mainly achieved by balancing the renin-angiotensin system, improving renal and cardiac impairment, and regulating endothelial dysfunction. These findings suggested that garlic proteins were potentially suitable materials to prepare ACE inhibitory peptides and provided two promising candidates for ACE inhibition as functional food ingredients.
Topics: Rats; Animals; Antihypertensive Agents; Peptidyl-Dipeptidase A; Angiotensin-Converting Enzyme Inhibitors; Garlic; Peptides; Rats, Inbred SHR; Biological Products; Protein Hydrolysates; Hypertension; Molecular Docking Simulation
PubMed: 37797452
DOI: 10.1016/j.foodchem.2023.137537