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The American Journal of Pathology Oct 2020Coronavirus disease 2019 has markedly varied clinical presentations, with most patients being asymptomatic or having mild symptoms. However, severe acute respiratory... (Review)
Review
Coronavirus disease 2019 has markedly varied clinical presentations, with most patients being asymptomatic or having mild symptoms. However, severe acute respiratory disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is common and associated with mortality in patients who require hospitalization. The etiology of susceptibility to severe lung injury remains unclear. Angiotensin II, converted by angiotensin-converting enzyme (ACE) from angiotensin I and metabolized by ACE 2 (ACE2), plays a pivotal role in the pathogenesis of lung injury. ACE2 is identified as an essential receptor for SARS-CoV-2 to enter the cell. The binding of ACE2 and SARS-CoV-2 leads to the exhaustion and down-regulation of ACE2. The interaction and imbalance between ACE and ACE2 result in an unopposed angiotensin II. Considering that the ACE insertion (I)/deletion (D) gene polymorphism contributes to the ACE level variability in general population, in which mean ACE level in DD carriers is approximately twice that in II carriers, we propose a hypothesis of genetic predisposition to severe lung injury in patients with coronavirus disease 2019. It is plausible that the ACE inhibitors and ACE receptor blockers may have the potential to prevent and to treat the acute lung injury after SARS-CoV-2 infection, especially for those with the ACE genotype associated with high ACE level.
Topics: Angiotensin I; Angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Animals; Betacoronavirus; COVID-19; Coronavirus Infections; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Lung Injury; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Polymorphism, Genetic; Receptors, Virus; Renin-Angiotensin System; SARS-CoV-2
PubMed: 32735889
DOI: 10.1016/j.ajpath.2020.07.009 -
Endocrine, Metabolic & Immune Disorders... 2022Angiotensin-converting enzyme (ACE) is a zinc-dependent dicarboxypeptidase with two catalytic components, which has an important role in regulating blood pressure by... (Review)
Review
Angiotensin-converting enzyme (ACE) is a zinc-dependent dicarboxypeptidase with two catalytic components, which has an important role in regulating blood pressure by converting angiotensin I to angiotensin II. ACE breaks down other peptides besides angiotensin I and has a variety of physiological effects together with renal growth and reproduction in men. ACE also acts on innate and acquired immune systems by affecting macrophage and neutrophil function, and these outcomes are exacerbated due to the overexpression of ACE. Overexpression of ACE in macrophages imposes antitumor and antimicrobial response, and it enhances the ability of neutrophils to produced super peroxide that has a bactericidal effect. ACE is also known to contribute to the expression of Major Histocompatibility Complex (MHC) class I and MHC class II peptides through enzymatic alterations of these peptides. Apprehending the expression of ACE and its effects on myeloid cell (myelogenous cells) activity can be promising in therapeutic interventions, including treatment of infection and malignancy.
Topics: Angiotensins; Animals; Antigen Presentation; Female; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Humans; Immunity; Infections; Macrophages; Male; Neoplasms; Peptidyl-Dipeptidase A
PubMed: 33583391
DOI: 10.2174/1871530321666210212144511 -
Molecular and Cellular Endocrinology Jun 2021Kidney disease, blood pressure determination, hypertension pathogenesis, and the renin-angiotensin system (RAS) are inextricably linked. Hence, understanding the RAS is... (Review)
Review
Kidney disease, blood pressure determination, hypertension pathogenesis, and the renin-angiotensin system (RAS) are inextricably linked. Hence, understanding the RAS is pivotal to unraveling the pathophysiology of hypertension and the determinants to maintaining normal blood pressure. The RAS has been the subject of intense investigation for over a century. Moreover, medications that block the RAS are mainstay therapies in clinical medicine and have been shown to reduce morbidity and mortality in patients with diabetes, cardiovascular, and kidney diseases. The main effector peptide of the RAS is the interaction of the octapeptide- Ang II with its receptor. The type 1 angiotensin receptor (ATR) is the effector receptor for Ang II. These G protein-coupled receptors (GPCRs) are ubiquitously expressed in a variety of cell lineages and tissues relevant to cardiovascular disease throughout the body. The advent of cell specific deletion of genes using Cre LoxP technology in mice has allowed for the identification of discreet actions of ATRs in blood pressure control and kidney disease. The kidney is one of the major targets of the RAS, which is responsible in maintaining fluid, electrolyte balance, and blood pressure. In this review we will discuss the role of ATRs in the kidney, vasculature, and immune cells and address their effects on hypertension and kidney disease.
Topics: Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme 2; Animals; Blood Pressure; Gene Expression Regulation; Humans; Hypertension; Kidney Tubules, Proximal; Mice; Mice, Knockout; Peptide Fragments; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renal Insufficiency, Chronic; Renin-Angiotensin System; Signal Transduction; Water-Electrolyte Balance
PubMed: 33781840
DOI: 10.1016/j.mce.2021.111259 -
Critical Care (London, England) Feb 2020In patients with vasodilatory shock, plasma concentrations of angiotensin I (ANG I) and II (ANG II) and their ratio may reflect differences in the response to severe...
BACKGROUND
In patients with vasodilatory shock, plasma concentrations of angiotensin I (ANG I) and II (ANG II) and their ratio may reflect differences in the response to severe vasodilation, provide novel insights into its biology, and predict clinical outcomes. The objective of these protocol prespecified and subsequent post hoc analyses was to assess the epidemiology and outcome associations of plasma ANG I and ANG II levels and their ratio in patients with catecholamine-resistant vasodilatory shock (CRVS) enrolled in the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) study.
METHODS
We measured ANG I and ANG II levels at baseline, calculated their ratio, and compared these results to values from healthy volunteers (controls). We dichotomized patients according to the median ANG I/II ratio (1.63) and compared demographics, clinical characteristics, and clinical outcomes. We constructed a Cox proportional hazards model to test the independent association of ANG I, ANG II, and their ratio with clinical outcomes.
RESULTS
Median baseline ANG I level (253 pg/mL [interquartile range (IQR) 72.30-676.00 pg/mL] vs 42 pg/mL [IQR 30.46-87.34 pg/mL] in controls; P < 0.0001) and median ANG I/II ratio (1.63 [IQR 0.98-5.25] vs 0.4 [IQR 0.28-0.64] in controls; P < 0.0001) were elevated, whereas median ANG II levels were similar (84 pg/mL [IQR 23.85-299.50 pg/mL] vs 97 pg/mL [IQR 35.27-181.01 pg/mL] in controls; P = 0.9895). At baseline, patients with a ratio above the median (≥1.63) had higher ANG I levels (P < 0.0001), lower ANG II levels (P < 0.0001), higher albumin concentrations (P = 0.007), and greater incidence of recent (within 1 week) exposure to angiotensin-converting enzyme inhibitors (P < 0.00001), and they received a higher norepinephrine-equivalent dose (P = 0.003). In the placebo group, a baseline ANG I/II ratio <1.63 was associated with improved survival (hazard ratio 0.56; 95% confidence interval 0.36-0.88; P = 0.01) on unadjusted analyses.
CONCLUSIONS
Patients with CRVS have elevated ANG I levels and ANG I/II ratios compared with healthy controls. In such patients, a high ANG I/II ratio is associated with greater norepinephrine requirements and is an independent predictor of mortality, thus providing a biological rationale for interventions aimed at its correction.
TRIAL REGISTRATION
ClinicalTrials.gov identifier NCT02338843. Registered 14 January 2015.
Topics: Angiotensin I; Angiotensin II; Catecholamines; Female; Humans; Male; Shock
PubMed: 32028998
DOI: 10.1186/s13054-020-2733-x -
Frontiers in Pharmacology 2020The importance of dietary potassium in health and disease has been underestimated compared with that placed on dietary sodium. Larger effort has been made on reduction...
BACKGROUND
The importance of dietary potassium in health and disease has been underestimated compared with that placed on dietary sodium. Larger effort has been made on reduction of sodium intake and less on the adequate dietary potassium intake, although natural food contains much more potassium than sodium. The benefits of a potassium-rich diet are known, however, the mechanism by which it exerts its preventive action, remains to be elucidated. With the hypothesis that dietary potassium reduces renal vasoconstrictor components of the renin-angiotensin system in the long-term, we studied the effect of high potassium diet on angiotensin-I converting enzyme, renin, and angiotensin converting enzyme 2.
METHODS
Sprague Dawley male rats on a normal sodium diet received normal potassium (0.9%, NK) or high potassium diet (3%, HK) for 4 weeks. Urine was collected in metabolic cages for electrolytes and urinary volume measurement. Renal tissue was used to analyze angiotensin-I converting enzyme, renin, and angiotensin converting enzyme 2 expression. Protein abundance analysis was done by Western blot; gene expression by mRNA levels by RT-qPCR. Renal distribution of angiotensin-I converting enzyme and renin was done by immunohistochemistry and morphometric analysis in coded samples.
RESULTS
High potassium diet (4 weeks) reduced the levels of renin, angiotensin-I converting enzyme, and angiotensin converting enzyme 2. Angiotensin-I converting enzyme was located in the brush border of proximal tubules and with HK diet decreased the immunostaining intensity ( < 0.05), decreased the mRNA ( < 0.01) and the protein levels ( < 0.01). Renin localization was restricted to granular cells of the afferent arteriole and HK diet decreased the number of renin positive cells ( < 0.01) and renin mRNA levels ( < 0.01). High potassium intake decreased angiotensin converting enzyme 2 gene expression and protein levels ( < 0.01).No morphological abnormalities were observed in renal tissue during high potassium diet.The reduced expression of angiotensin-I converting enzyme, renin, and angiotensin converting enzyme 2 during potassium supplementation suggest that high dietary potassium intake could modulate these vasoactive enzymes and this effects can contribute to the preventive and antihypertensive effect of potassium.
PubMed: 32625100
DOI: 10.3389/fphar.2020.00920 -
Arquivos Brasileiros de Oftalmologia Aug 2020The renin-angiotensin system is involved in the pathogenesis of retinal ischemic conditions and glaucoma. Our objective was to evaluate the renin, angiotensinconverting...
PURPOSE
The renin-angiotensin system is involved in the pathogenesis of retinal ischemic conditions and glaucoma. Our objective was to evaluate the renin, angiotensinconverting enzyme 1, and angiotensin-converting enzyme 2 activities in aqueous humor and blood samples of patients with and without primary open-angle glaucoma.
METHODS
We analyzed samples from 56 participants who underwent ocular surgeries. The patients were divided into two groups: patients with cataract alone (n=28) and patients with cataract and primary open-angle glaucoma (n=28). Venous blood (2 ml) and aqueous humor (150 µl, via paracentesis) samples were collected during phacoemulsification (cataract only) or glaucoma surgery (cataract and primary open-angle glaucoma). The serum and aqueous humor renin, angiotensin-converting enzyme 1, and angiotensin-converting enzyme 2 activities of all patients were evaluated by fluorimetric assays, and results were analyzed by using multivariate regression analysis.
RESULTS
Both the aqueous humor renin activity and renin activity aqueous humor/serum ratio were significantly lower in patients with cataract and primary open-angle glaucoma than in patients with cataract only [(mean ± SE): 0.018 ± 0.006 ng/ml/h vs 0.045 ± 0.009 ng/ml/h, p<0.001; 0.05 ± 0.02 vs 0.13 ± 0.05, p=0.025]. Multivariate analyses showed a significant relationship between lower aqueous humor renin activity and primary open-angle glaucoma [coefficient (±SE): -0.029 ± 0.013, p=0.026].
CONCLUSIONS
Our results showed that patients with primary open-angle glaucoma had lower aqueous humor renin activity. As timolol eye drops were used by most of the primary open-angle glaucoma patients, we propose that a large sample of washed-out patients should be studied in the future to discriminate the involvement of b-blocker treatment in the aqueous humor renin activity.
Topics: Angiotensin I; Angiotensin II; Aqueous Humor; Cataract; Glaucoma, Open-Angle; Humans; Renin
PubMed: 32756783
DOI: 10.5935/0004-2749.20200052 -
Bioscience Reports Sep 2019The renin-angiotensin system (RAS) is undisputedly well-studied as one of the oldest and most critical regulators for arterial blood pressure, fluid volume, as well as... (Review)
Review
The renin-angiotensin system (RAS) is undisputedly well-studied as one of the oldest and most critical regulators for arterial blood pressure, fluid volume, as well as renal function. In recent studies, RAS has also been implicated in the development of obesity, diabetes, hyperlipidemia, and other diseases, and also involved in the regulation of several signaling pathways such as proliferation, apoptosis and autophagy, and insulin resistance. AMP-activated protein kinase (AMPK), an essential cellular energy sensor, has also been discovered to be involved in these diseases and cellular pathways. This would imply a connection between the RAS and AMPK. Therefore, this review serves to draw attention to the cross-talk between RAS and AMPK, then summering the most recent literature which highlights AMPK as a point of balance between physiological and pathological functions of the RAS.
Topics: AMP-Activated Protein Kinases; Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme 2; Autophagy; Blood Pressure; Blood Vessels; Gene Expression Regulation; Humans; Insulin Resistance; Kidney; Muscle, Skeletal; Myocardium; Peptidyl-Dipeptidase A; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renin-Angiotensin System; Signal Transduction
PubMed: 31413168
DOI: 10.1042/BSR20181994 -
Molecular Human Reproduction Jun 2020The 2019 novel coronavirus (2019-nCoV) appeared in December 2019 and then spread throughout the world rapidly. The virus invades the target cell by binding to... (Review)
Review
The 2019 novel coronavirus (2019-nCoV) appeared in December 2019 and then spread throughout the world rapidly. The virus invades the target cell by binding to angiotensin-converting enzyme (ACE) 2 and modulates the expression of ACE2 in host cells. ACE2, a pivotal component of the renin-angiotensin system, exerts its physiological functions by modulating the levels of angiotensin II (Ang II) and Ang-(1-7). We reviewed the literature that reported the distribution and function of ACE2 in the female reproductive system, hoping to clarify the potential harm of 2019-nCoV to female fertility. The available evidence suggests that ACE2 is widely expressed in the ovary, uterus, vagina and placenta. Therefore, we believe that apart from droplets and contact transmission, the possibility of mother-to-child and sexual transmission also exists. Ang II, ACE2 and Ang-(1-7) regulate follicle development and ovulation, modulate luteal angiogenesis and degeneration, and also influence the regular changes in endometrial tissue and embryo development. Taking these functions into account, 2019-nCoV may disturb the female reproductive functions through regulating ACE2.
Topics: Adult; Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme 2; Betacoronavirus; COVID-19; Coronavirus Infections; Female; Gene Expression Regulation; Genitalia, Female; Host-Pathogen Interactions; Humans; Pandemics; Peptide Fragments; Peptidyl-Dipeptidase A; Pneumonia, Viral; Pregnancy; Protein Binding; Receptors, Virus; Renin-Angiotensin System; SARS-CoV-2; Spike Glycoprotein, Coronavirus
PubMed: 32365180
DOI: 10.1093/molehr/gaaa030 -
Current Hypertension Reports Jul 2020To review recent data that suggest opposing effects of brain angiotensin type-1 (ATR) and type-2 (ATR) receptors on blood pressure (BP). Here, we discuss recent studies... (Review)
Review
PURPOSE OF REVIEW
To review recent data that suggest opposing effects of brain angiotensin type-1 (ATR) and type-2 (ATR) receptors on blood pressure (BP). Here, we discuss recent studies that suggest pro-hypertensive and pro-inflammatory actions of ATR and anti-hypertensive and anti-inflammatory actions of ATR. Further, we propose mechanisms for the interplay between brain angiotensin receptors and neuroinflammation in hypertension.
RECENT FINDINGS
The renin-angiotensin system (RAS) plays an important role in regulating cardiovascular physiology. This includes brain ATR and ATR, both of which are expressed in or adjacent to brain regions that control BP. Activation of ATR within those brain regions mediate increases in BP and cause neuroinflammation, which augments the BP increase in hypertension. The fact that ATR and ATR have opposing actions on BP suggests that ATR and ATR may have similar opposing actions on neuroinflammation. However, the mechanisms by which brain ATR and ATR mediate neuroinflammatory responses remain unclear. The interplay between brain angiotensin receptor subtypes and neuroinflammation exacerbates or protects against hypertension.
Topics: Angiotensin I; Brain; Humans; Hypertension; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin
PubMed: 32661792
DOI: 10.1007/s11906-020-01062-0 -
Comprehensive Reviews in Food Science... Mar 2021Angiotensin-I-converting enzyme (ACE) inhibitory peptides are able to inhibit the activity of ACE, which is the key enzymatic factor mediating systemic hypertension....
Angiotensin-I-converting enzyme (ACE) inhibitory peptides are able to inhibit the activity of ACE, which is the key enzymatic factor mediating systemic hypertension. ACE-inhibitory peptides can be obtained from edible proteins and have the function of antihypertension. The amino acid sequences and the secondary structures of ACE-inhibitory peptides determine the inhibitory activities and stability. The resistance of ACE-inhibitory peptides to digestive enzymes and peptidase affect their antihypertensive bioactivity in vivo. In this paper, the mechanism of ACE-inhibition, sources of the inhibitory peptides, structure-activity relationships, stability during digestion, absorption and transportation of ACE-inhibitory peptides, and consumption of ACE-inhibitory peptides are reviewed, which provide guidance to the development of new functional foods and production of antihypertensive nutraceuticals and pharmaceuticals.
Topics: Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Biological Availability; Peptides; Peptidyl-Dipeptidase A
PubMed: 33527706
DOI: 10.1111/1541-4337.12711