Lower Angiotensin-converting Enzyme Research Articles

A Retrospective Study to Evaluate the Association Between the Glasgow Prognostic Score and Atrial Fibrillation, Stroke, and Mortality at 30 Days and at 1 Year After Coronary Artery Bypass Graft Surgery.

BACKGROUND The Glasgow prognostic score (GPS) consists of a combination of serum C-reactive protein and albumin levels as indicators of systematic inflammatory response and nutritional status, respectively. The present retrospective study aimed to evaluate the association between the GPS and atrial fibrillation, stroke, and mortality at 30 days and 1 year after coronary artery bypass graft (CABG) surgery. MATERIAL AND METHODS Patients with chronic coronary syndromes who underwent CABG surgery between 2012 and 2019 in a single center were included. Preoperative GPS was calculated. Then, patients were grouped according to postoperative atrial fibrillation (POAF) development. Further, groups were formed to evaluate the relationship between GPS and 30-day and 1-year cardiovascular mortality as well as stroke development. RESULTS Patients who developed POAF had higher GPS, higher European System for Cardiac Operative Risk Evaluation (EuroSCORE II) score, advanced age, lower angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) use, lower left ventricular ejection fraction, and were more likely to be female and to have a history of carotid artery disease (P<0.05, for all). Additionally, GPS, EuroSCORE II, advanced age, and lower left ventricular ejection fraction were detected as independent risk factors for POAF development. When adverse outcomes were assessed, cardiovascular mortality at 30 days or 1 year, and stroke development at 1 year, were more frequent in patients with POAF. Moreover, POAF development was found to be an independent risk factor for adverse outcomes. Also, GPS was established as an independent risk factor both for 30-day and 1-year cardiovascular mortality (P<0.0001 and P=0.001, respectively). CONCLUSIONS GPS is an easy-to-calculate score that has reasonable diagnostic accuracy in determining the risk of POAF and stroke as well as 30-day and 1-year cardiovascular mortality.

The Effect of Soybean Peptides on Improving Quality and the ACE Inhibitory Bioactivity of Extruded Rice

It is crucial to address the dietary problems of hypertensive patients. The effect and mechanism of different contents of soybean protein on cooking quality and angiotensin-converting enzyme (ACE) inhibitory action in the extruded rice were firstly investigated. The results showed that the extruded rice with soybean protein possessed the higher taste value (90.32 ± 2.31), hardness (2.65 ± 0.01 g), and good pasting quality (p ≤ 0.05). Meanwhile, the soybean protein notably retarded the starch digestibility; the sample with 6% soybean protein showed the fewest rapidly digestible starch (RDS) content (78.82 ± 0.01 mg g−1) and the most slowly digestible starch (SDS) content (8.97 ± 0.45 mg g−1). Importantly, the ACE inhibition rate improved from 17.09 ± 0.01% to 74.02 ± 0.65% in the 6% soybean protein sample because of the production of peptides. The peptide composition of samples were compared, which showed that the effective ACE-inhibitory peptides usually contain 2~20 amino acids, and Pro, Leu, Ile, Val, Phe, and Ala were the main components. Overall, moderate soybean protein would give a good quality and lower ACE activity in extruded food.

Low placental angiotensin-converting enzyme expression is related to fetal small for gestational age but not to metabolic control in type 1 diabetic pregnancies.

The maternal renin-angiotensin system is involved in blood pressure control and plays a crucial role in fetoplacental nutrition. Pre-gestational type 1 diabetes (PGDM) leads to serious pregnancy complications. We thus performed a longitudinal study to analyse the association of maternal angiotensin-converting enzyme (ACE) serum levels and placental mRNA expression with fetal newborns gestational weight in type 1 diabetes mellitus (T1DM) women. We recruited 65 singleton pregnant women with T1DM. Placental mRNA ACE gene expression was examined using quantitative real-time PCR. Serum ACE levels were measured in the first, second and third trimesters of pregnancy by ELISA commercial kits. Placental expression of ACE mRNA was significantly lower in small for gestational age (SGA) than appropriate for gestational age (AGA) and large for gestational age (LGA) mothers (0.55±0.06 vs 0.78±0.06 and 0.85±0.07 respectively, p=0.003). In the SGA group, the mRNA expression of ACE positively correlated with maternal body mass index (BMI) in the third trimester (r=0.49; p=0.04). In all study groups maternal ACE level was significantly higher in the third trimester (mean 139.91±SD 69.64) compared to the first and second trimesters of pregnancy (13.57±4.32 and 15.69±15.92 respectively). Our data suggest that lower placental ACE gene mRNA expression may have a vital role in the etiology of SGA babies.

The potential role of renin-angiotensin system in mild traumatic brain injury.

Traumatic brain injury (TBI) is a serious public health problem, affecting 69 million people worldwide annually. Mild TBI (mTBI) comprises the majority of the cases and remains the most neglected TBI severity. Its intricate pathophysiology involves complex cellular and molecular processes that remain uncomprehended. Although the renin-angiotensin system (RAS) has its well-known roles in blood pressure regulation and fluid balance, accumulating evidence demonstrates its active expression and signaling in the central nervous system. Over the past years, pre-clinical studies have been supporting the role of RAS in mTBI. However, particularly for human TBI, evidence is still missing. Herein, we investigated peripheral levels of angiotensin II (Ang II) and angiotensin-converting enzyme (ACE), components of RAS classical axis, as well as angiotensin-(1-7) [Ang-(1-7)] and ACE2, components of RAS counter-regulatory axis, in 28 mTBI patients and 24 healthy controls. In the first 24h, mTBI patients displayed lower ACE (p = 0.0004) and ACE2 (p = 0.0047) concentrations and an increase in Ang II (p = 0.0234) and Ang-(1-7) (p = 0.0225) levels compared to controls. Interestingly, at 30days follow-up, mTBI patients increased the levels of ACE (p = 0.0415) and ACE2 (p = 0.0416) along with a decrease in Ang II (p = 0.0039) and Ang-(1-7) (p = 0.0015) concentrations compared with their measures at 24h after TBI. Also, our receiver operating curve (ROC) analysis demonstrated that ACE concentration was a good predictor of mTBI diagnosis (AUC = 0.798, p < 0.0001). The current study provides the first clinical evidence of RAS molecule's involvement in mTBI and their possible role as discriminating biomarkers.

Norepinephrine acting on adventitial fibroblasts stimulates vascular smooth muscle cell proliferation via promoting small extracellular vesicle release.

Excessive sympathetic activity and norepinephrine (NE) release play crucial roles in the pathogeneses of hypertension. Sympathetic fibers innervate adventitia rather than media of arteries. However, the roles of NE in adventitial fibroblasts (AFs) are unknown. This study investigated the roles of NE in regulating AFs-derived extracellular vesicles (EVs) release and vascular smooth muscle cells (VSMCs) proliferation in hypertension.Methods: AFs and VSMCs were prepared from aorta of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). AFs were treated with NE (10 μM) for 24 h (every 6 h, 4 times), and cultured in exosomes-depleted medium for 48 h. EVs were isolated from AFs medium with ultracentrifugation for identification and transfer to VSMCs.Results: NE promoted AFs phenotypic transformation and proliferation, which were prevented by α-receptor antagonist phentolamine rather than β-receptor antagonist propranolol. NE-treated AFs conditioned medium stimulated VSMCs proliferation, which was inhibited by either exosome inhibitor GW4869 or phentolamine. NE increased small EVs number, diameter and angiotensin converting enzyme (ACE) contents. The NE-induced EVs release was abolished by GW4869. The EVs from NE-treated AFs stimulated VSMCs proliferation, which was prevented by angiotensin II type 1 receptor antagonist losartan. The EVs from the ACE knockdown-treated AFs showed lower ACE contents, and lost their roles in stimulating VSMCs proliferation.Conclusion: NE promotes AFs-derived small EVs release and ACE transfer, and then causes VSMCs proliferation in hypertension. Intervention of AFs-derived EVs release may be potential therapeutics for excessive sympathetic activation-related vascular remodeling in hypertension.

Structure-function relationship of fermented skate skin gelatin-derived bioactive peptides: a peptidomics approach.

The online version contains supplementary material available at 10.1007/s10068-021-00998-6.

Lower Serum Angiotensin-Converting Enzyme Level in Relation to Hyperinflammation and Impaired Antiviral Immune Response Contributes to Progression of COVID-19 Infection.

IntroductionAs a homologue of the angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2) has been identified as the main receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invasion. We aimed to investigate the role of serum ACE in predicting the coronavirus disease 2019 (COVID-19) disease progression and the underlying mechanisms.MethodsWe retrospectively enrolled 120 patients with confirmed COVID-19 who underwent serum ACE detection on admission. The clinical characteristics and laboratory findings during hospitalization were evaluated dynamically to identify the potential risk factors for disease progression.ResultsACE level was demonstrated as one of the independent risk factors. Patients with ACE level ≤ 33.5 U/L showed a higher cumulative virus RNA detection rate, elevated pro-inflammatory mediators levels, declined lymphocyte count, and decreased SARS-CoV-2-specific antibodies than those with ACE level > 33.5 U/L.ConclusionLower serum ACE levels in relation to delayed virus elimination, hyperinflammatory condition, and impaired host antiviral immune responses contribute to disease progression of COVID-19.

Association of Antihypertensive Drug Target Genes With Psychiatric Disorders

Observational studies have reported associations between antihypertensive medication and psychiatric disorders, although the reported direction of association appears to be dependent on drug class. To estimate the potential effect of different antihypertensive drug classes on schizophrenia, bipolar disorder, and major depressive disorder. This 2-sample mendelian randomization study assessed the association between a single-nucleotide variant (SNV) and drug target gene expression derived from existing expression quantitative trait loci (eQTL) data in blood (sample 1) and the SNV-disease association from published case-control genome-wide association studies (sample 2). Significant associations were corroborated using published brain eQTL and protein QTL data. Participants included 40 675 patients with schizophrenia and 64 643 controls, 20 352 patients with bipolar disorder and 31 358 controls, and 135 458 patients with major depressive disorder and 344 901 controls. Blood eQTL levels were measured in 31 684 individuals from 37 cohorts (eQTLGen consortium); prefrontal cortex eQTLs were measured from the PsychENCODE resource in 1387 individuals; and protein QTLs were measured in cerebral spinal fluid from 544 individuals and plasma from 818 individuals. Data were collected from October 4, 2019, to June 1, 2020, and analyzed from October 14, 2019, to June 6, 2020. Expression levels of antihypertensive drug target genes as proxies for drug exposure, and genetic variants robustly associated with the expression of these genes as mendelian randomization instruments. Risk for schizophrenia, bipolar disorder, and major depressive disorder. A 1-SD lower expression of the angiotensin-converting enzyme (ACE) gene in blood was associated with lower systolic blood pressure of 4.0 (95% CI, 2.7-5.3) mm Hg, but increased risk of schizophrenia (odds ratio [OR], 1.75; 95% CI, 1.28-2.38; P = 3.95 × 10-4). A concordant direction of association was also observed between ACE expression in prefrontal cortex (OR, 1.33; 95% CI, 1.13-1.56) and ACE protein levels in cerebral spinal fluid (OR per 1-SD decrease, 1.12; 95% CI, 1.05-1.19) and plasma (OR per 1-SD decrease, 1.04; 95% CI, 1.01-1.07). We found no evidence for an association between genetically estimated SBP and schizophrenia risk. Findings suggest an adverse association of lower ACE messenger RNA and protein levels with schizophrenia risk. These findings warrant greater pharmacovigilance and further investigation into the effect of ACE inhibitors, particularly those that are centrally acting, on psychiatric symptoms in patients with schizophrenia, as well as the role of ACE inhibitor use in late-onset schizophrenia.

Decreased Plasma Levels of Angiotensin-Converting Enzyme Among Patients With Bipolar Disorder.

BackgroundDysfunctions in the renin-angiotensin system (RAS) seem to be involved in the pathophysiology of several mental illness, including schizophrenia and mood disorders. We carried out a cross-sectional study assessing the levels of RAS-related molecules among bipolar disorder (BD) patients compared to healthy controls.Methodsour sample consisted of 30 outpatients with BD type 1 (10 males, 20 females, age = 35.53 ± 10.59 years, 14 euthymic, 16 experiencing mood episodes) and 30 healthy controls (10 males, 20 females, age = 34.83 ± 11.49 years). Plasma levels of angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin-II (Ang II), and angiotensin (1–7) [Ang-(1–7)] were determined by ELISA.ResultsBD patients experiencing ongoing mood episodes had significantly lower ACE levels compared to controls (median: 459.00 vs. 514.10, p < 0.05). There was no association between the levels of these biomarkers and clinical parameters.ConclusionOur findings support the involvement of RAS dysfunction in the pathophysiology of BD. Considering the potential therapeutic implications linked to a better understanding of the role of RAS dysfunction in BD, studies allowing a better characterization of RAS-related molecules level and activity across different mood states are of high interest.

Effects of enzymatically hydrolysed poultry byproduct meal in extruded diets on serum angiotensin-converting enzyme activity and aldosterone in cats

ABSTRACT Several peptides found in hydrolysed poultry byproduct meal can inhibit angiotensin-converting enzyme (ACE) activity, a property that indicates potential antihypertensive and health-promoting effects. This study aimed to assess the effects of extruded diets containing enzymatically hydrolysed poultry byproduct meal (HPM) on cat serum ACE activity and aldosterone (ALD) concentration, nutrient digestibility, and faecal characteristics. On the basis of a preliminary in vitro ACE inhibitory activity assay, a commercial HPM and a commercial conventional poultry byproduct meal (CPM) were selected for further investigation. Two isoenergetic and isonitrogenous diets were formulated: CPM diet (25.7% CPM) and HPM diet (24.7% HPM). In trial 1, the effect of diet on serum ACE activity and ALD concentration was evaluated using 8 healthy cats (4 female and 4 male, 4.1 ± 0.38 kg BW) in a crossover design, with 5 d of adaptation and blood collection on d 6. In trial 2, apparent total tract digestibility and faecal characteristics were evaluated using 12 cats (6 female and 6 male, 4.0 ± 0.72 kg BW) in a completely randomised design. Serum ACE and ALD were analysed using a mixed model, with diet as the fixed effect and cat as the random effect. Data from trial 2 were subjected to analysis of variance, and means were compared by Tukey’s test. In vitro ACE inhibitory activity of HPM (90.4%) was higher than that of CPM (52.0%). Cats fed the HPM diet tended to have lower serum ACE activity than those fed the CPM diet (126 versus 142 U/l, p = 0.09). Serum ALD was not influenced by diet. Diets had similar digestibility values, and faecal consistency scores tended to be higher (firmer faeces) in cats fed the CPM diet than in cats fed the HPM diet (4.6 versus 4.0, p = 0.09). Inclusion of HPM in extruded diets may reduce cat serum ACE activity and promote good faecal consistency without affecting digestibility. Further investigations are needed to explore the potential health benefits of HPM in hypertensive cats.

Antioxidant, hypoglycemic and anti-hypertensive properties of extracts derived from peel, fruit and kernel of Salak

PurposeSalak (Salacca zalacca) is an underutilised fruit. The bioactivities of this fruit have rarely been studied scientifically. Thus, the present study aimed to determine the antioxidant activity of extracts derived from the peel, fruit and kernel of the Salak fruit, as well as the hypoglycemic and anti-hypertensive properties of Salak peel extracts.Design/methodology/approachThe peel, fruit and kernel of the Salak were extracted using distilled water, methanol and ethanol. Antioxidant activities, angiotensin-converting enzyme (ACE) and alpha-amylase inhibition properties of the extracts were estimated via in vitro standard methods. Besides, the total phenolic content (TPC) and total flavonoid content (TFC) of the extracts were also determined in the present study. The antioxidant activities of different parts of Salak extracts were determined by ferric-reducing antioxidant power (FRAP) and Trolox equivalent antioxidant capacity (TEAC) methods. Percent of radical scavenging properties were calculated via DPPH assay. The hypoglycemic and anti-hypertensive properties of Salak peel were evaluated using alpha-amylase inhibition and ACE assays, respectively.FindingsFruit extracts of Salak in methanol were found to exhibit the highest TPC (10.27 ± 0.12 mg GAE/g), TFC (11.04 ± 0.89 mg CE/g) and antioxidant properties amongst all samples whereby the TPC and TFC were strongly correlated with antioxidant activities. On the other hand, distilled water extracted Salak kernel showed to have the lowest TPC (0.53 ± 0.05 mg GAE/g), TFC (0.37 ± 0.01 mg CE/g) and antioxidant properties amongst all the Salak extracts. Peel extracts exhibit comparable antioxidant activities with fruit extracts in the current findings. In addition, peel extracts indicated some extend of ACE and alpha-amylase inhibition activities regardless of the solvents used. Methanol and ethanol peel extracts indicated no significant difference (p < 0.05) ACE (98%) and alpha-amylase (90%) inhibition activities. However, distilled water extracted Salak peel showed significantly lower ACE and alpha-amylase inhibition in comparison to methanol and ethanol peel extracts.Originality/valueThe present findings suggested that the fruit of Salak exhibits the highest antioxidant properties, followed by the peel and lastly, the kernel, which shows the lowest antioxidant properties amongst all the samples. The results also indicated that the peel extracts have ACE and alpha-amylase inhibition activities.

Pediatric Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Clinical Presentation, Infectivity, and Immune Responses

ObjectivesAs schools plan for re-opening, understanding the potential role children play in the coronavirus infectious disease 2019 (COVID-19) pandemic and the factors that drive severe illness in children is critical.Study designChildren ages 0-22 years with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presenting to urgent care clinics or being hospitalized for confirmed/suspected SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) at Massachusetts General Hospital were offered enrollment in the Massachusetts General Hospital Pediatric COVID-19 Biorepository. Enrolled children provided nasopharyngeal, oropharyngeal, and/or blood specimens. SARS-CoV-2 viral load, ACE2 RNA levels, and serology for SARS-CoV-2 were quantified.ResultsA total of 192 children (mean age, 10.2 ± 7.0 years) were enrolled. Forty-nine children (26%) were diagnosed with acute SARS-CoV-2 infection; an additional 18 children (9%) met the criteria for MIS-C. Only 25 children (51%) with acute SARS-CoV-2 infection presented with fever; symptoms of SARS-CoV-2 infection, if present, were nonspecific. Nasopharyngeal viral load was highest in children in the first 2 days of symptoms, significantly higher than hospitalized adults with severe disease (P = .002). Age did not impact viral load, but younger children had lower angiotensin-converting enzyme 2 expression (P = .004). Immunoglobulin M (IgM) and Immunoglobulin G (IgG) to the receptor binding domain of the SARS-CoV-2 spike protein were increased in severe MIS-C (P < .001), with dysregulated humoral responses observed.ConclusionsThis study reveals that children may be a potential source of contagion in the SARS-CoV-2 pandemic despite having milder disease or a lack of symptoms; immune dysregulation is implicated in severe postinfectious MIS-C.

Current trends in bioactive peptides from muscle foods and their potential application

Muscle protein is a valuable source of energy and essential amino acids, which are needed for growth and maintenance of physiological functions. It also provides peptides known as bioactive peptides exerting some health benefits, including antihypertension, antioxidant activity, immunomodulatory activity, and improving brain function, among others. Bioactive peptides can be generated from digestion or enzymatic reaction. Cooking condition is found to critically affect digestibility of chicken breast and release of bioactive peptides. Extreme thermal treatment at 121°C/15 min reduces simulated gastrointestinal digestion (GI) of chicken breast. In addition, release of peptides inhibiting angiotensin converting enzyme (ACE) that regulates blood pressure via renin–angiotensin system decreases. This implies that extreme thermal process of muscle food lower nutritional values and available ACE inhibitor peptides. Enzymatic hydrolysis is also an effective means to produce bioactive peptides, providing appropriate protease(s) is applied under the optimal condition. Hydrolysates or bioactive peptides would likely be modified through GI digestion. Thus, changes of bioactivities upon GI digestion should be taken into consideration for optimization of protein hydrolysate production. Structural changes of bioactive peptides further take place during transepithelial transport. This would definitely affect bioactivities of peptides reaching the target organ in either positive or negative manner. To further develop functional food or nutraceutical products, efficacy of bioactive peptides should be tested in vivo to assure their health benefits.

240-LB: Angiotensin-Converting Enzyme and Type 2 Diabetes Risk: A Mendelian Randomization Study

The causal relationship between angiotensin-converting enzyme (ACE) inhibition and protection from type 2 diabetes (T2D) remains uncertain. While three large randomized control trials (RCTs) suggested a protective effect of ACE inhibitors compared to placebo, three other RCTs failed to observe an effect, including the only trial dedicated to this question. We hypothesized that ACE concentration-lowering genetic variants could be used to infer the pharmacological effect of ACE inhibitors on T2D risk using a Mendelian Randomization (MR) approach. We first assessed the association between T2D prevalence and ACE serum level in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial (N=8,197). We next investigated whether genetically lowered ACE level was causally linked to the risk of T2D using (i) a two-sample MR analysis applied to the DIAbetes Genetics Replication And Meta-analysis consortium (n=26,676 T2D cases; 132,532 controls), and (ii) an ACE concentration-lowering genetic risk score in the UK Biobank cohort (N=341,872). We then compared the genetically determined effect of lower ACE level on T2D risk to the pharmacological inhibition of ACE vs. placebo, which was evaluated through a meta-analysis of six RCTs (N=31,200). Lower ACE serum level was associated with reduced T2D prevalence (OR, 0.89; 95% CI, 0.82-0.96; P=3.50x10-3) in the ORIGIN trial. Through MR analyses, a 1 SD lower genetically determined ACE level predicted a lower risk of T2D (OR, 0.92; 95% CI, 0.89-0.95; P=1.79x10-7). This result was replicated in the UK Biobank (OR, 0.97; 95% CI, 0.96-0.99, P=8.73x10-4). RCT meta-analysis showed a reduction in T2D incidence on ACE inhibitors vs. placebo (OR, 0.76; 95% CI, 0.60-0.97; P=2.59x10-2), which was consistent with the findings from MR analyses (P for comparison=0.95). Our results support a protective effect of long-term ACE inhibition on T2D risk and suggest to consider patient's risk for T2D when prescribing blood-pressure lowering drugs. Disclosure M. Pigeyre: None. J. Sjaarda: None. M. Chong: None. S. Hess: None. J. Bosch: Advisory Panel; Self; Bayer AG. S. Yusuf: None. H. Gerstein: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Sanofi. G. Pare: Consultant; Self; Amgen Inc., Bristol-Myers Squibb Company, Lexicomp, Sanofi. Research Support; Self; Canada Research Chair in Genetic and Molecular Epidemiology, CISCO Professorship in Integrated Health Biosystems, Sanofi. Funding Sanofi; Canadian Institutes of Health Research

Preliminary study about the relationship between estimated training status and RAS polymorphisms on blood pressure and ACE activity in the elderly.

Objective:Polymorphisms of the renin angiotensin system (RAS) are associated with increases in blood pressure (BP). Physical exercise has been considered the main strategy to prevent this increase. This study aimed to investigate the relationship between estimated training status (TS), BP and angiotensin-converting enzyme (ACE) activity in elderly people classified as low or high risk to develop hypertension according to genetic profile.Methods:A total of 155 elderly participants performed the following assessments: general functional fitness index (GFFI), systolic BP (SBP) and diastolic BP (DBP), blood collection for ACE activity and analyses of the RAS polymorphisms.Results:Uncontrolled hypertensive (UHT) participants presented higher values of SBP and DBP compared with normotensive (NT) and controlled hypertensive (CHT) participants. No differences were found in ACE activity and GFFI between groups. In the high risk group, UHT presented higher values of SBP and DBP compared with other groups. CHT presented higher values of SBP compared with NT. Furthermore, UHT presented higher values of ACE activity compared with CHT and lower values of GFFI compared with NT.Conclusion:MDA, TIA and TIC genetic combinations were associated with high risk of developing hypertension while the maintenance of good levels of TS was associated with lower BP values and ACE activity.

The source of ACE during scar formation is from both bone marrow and skin tissue.

Angiotensin-converting enzyme (ACE) has been found in the pathogenesis of various fibrosis diseases, and ACE inhibitor (ACEI) may affect wound healing and cutaneous fibrosis. However, there is no scientific evidence as to where the ACE is produced during scar formation. Whether it is from the cutaneous tissue or the bone marrow, or both remains unknown. In this study, we investigated the source of ACE using bone marrow transplantation in genetically modified mice, analyzed the inflammatory milieu and some growth factors in the middle of the wound healing period (4 d after the wound was induced). After having deleted the ACE from bone marrow or skin tissue, the wound/scar width in the low-ACE groups were narrower than those in wild-type (WT) controls. Loosely arranged collagen deposition and reduced vessel density were also detected in ACE-deficient mice. Lower ACE levels during scar formation were also accompanied by lower levels of TGF-β1. In the middle of the wound healing period, ACE levels affected the inflammatory cells significantly. In the mice with a deficiency in ACE, the expression of TGF-β1 and TNF-α decreased, but not that of IL-4. Our findings indicate that both bone marrow and skin tissue release ACE during scar formation. Deleting either of them can affect the inflammatory cells and growth factors and reduce the expression of TGF-β1, resulting in a decreased level of scarring.-Fang, Q.-Q., Wang, X.-F., Zhao, W.-Y., Chen, C.-Y., Zhang, M.-X., Shi, B.-H., Zhang, L.-Y., Tan, W.-Q. The source of ACE during scar formation is from both bone marrow and skin tissue.

Effects of Pravastatin on Type 1 Diabetic Rat Heart with or without Blood Glycemic Control.

Although statins have been suggested to attenuate the progression of diabetic cardiomyopathy, its effect without glycemic control remains unclear. Therefore, we evaluated the effect of pravastatin on diabetic rat hearts according to glycemic control. Rats were randomly divided into five groups: control (C), diabetes (D), diabetes with insulin (I), diabetes with pravastatin (P), and diabetes with insulin and pravastatin (IP). Eight weeks after allocated treatments, the heart was extracted and analyzed following echocardiography. Cardiac fibrosis was measured using Masson's trichrome stain. Cardiac expression of collagen I/III, matrix metalloproteinase (MMP)-2, MMP-9, and angiotensin-converting enzyme (ACE)/ACE2 was evaluated by immunohistochemistry and/or Western blot. Enzyme-linked immunosorbent assay was used for measuring reactive oxygen species (ROS). Diabetic groups without glycemic control (D and P) showed significantly impaired diastolic function and increased levels of cardiac fibrosis, collagen I/III, MMP-2, MMP-9, and ROS production. However, there were little significant differences in the outcomes among the control and two glucose-controlled diabetic groups (I and IP). Groups C and IP showed more preserved ACE2 and lower ACE expressions than the other groups did (D, I, and P). Our study suggested glycemic control would be more important to attenuate the progression of diabetic cardiomyopathy than pravastatin medication.

Analysis of Age Distribution and Disease Presentation of 1269 Patients with Sarcoidosis.

While the incidence of sarcoidosis peaks between 20 and 39 years, it is comparatively low in elderly subjects. We sought to determine whether there are age-dependent differences in the demographic and laboratory characteristics of patients with sarcoidosis. We retrospectively collected information from our database using the International Classification of Disease (ICD) diagnostic code D86 between 2008 and 2014. Patients were divided into three groups: 20-39 years old (Group 1), 40-59 years old (Group 2), and 60-80 years old (Group 3). A total of 3988 patients with code of D86 were included in the study. After the exclusion of non-eligible patients, the number of cases in Groups 1, 2, and 3 were 276, 641, and 352, respectively. The groups were compared according to demographic characteristics, ICD diagnostic codes, and laboratory parameters. The ratio of female patients was significantly higher in Group 3 than in Groups 1 and 2 (p=0.000). There was no difference in diagnostic codes of the ICD subgroups between groups (p=0.19). While the level of blood-urea nitrogen was significantly higher in Group 3 patients than in other groups (p=0.000), serum angiotensin-converting enzyme (ACE) values were found to be significantly low in Group 3 (p=0.010). The mean ACE values did not differ between females and males (50.8±39.3 and 59.1±45.5 mg/dL, respectively) (p=0.18). The majority of patients with sarcoidosis were female in all age groups and pulmonary sarcoidosis was the most common presentation of the disease. Elderly patients (≥60 years) with sarcoidosis had lower serum ACE levels than younger patients.

Urine RAS components in mice and people with type 1 diabetes and chronic kidney disease.

The pathways implicated in diabetic kidney disease (DKD) are largely derived from animal models. To examine if alterations in renin-angiotensin system (RAS) in humans are concordant with those in rodent models, we measured concentration of angiotensinogen (AOG), cathepsin D (CTSD), angiotensin-converting enzyme (ACE), and ACE2 and enzymatic activities of ACE, ACE2, and aminopeptidase-A in FVB mice 13-20 wk after treatment with streptozotocin (n = 9) or vehicle (n = 15) and people with long-standing type 1 diabetes, with (n = 37) or without (n = 81) DKD. In streptozotocin-treated mice, urine AOG and CTSD were 10.4- and 3.0-fold higher than in controls, respectively (P < 0.001). Enzymatic activities of ACE, ACE2, and APA were 6.2-, 3.2-, and 18.8-fold higher, respectively, in diabetic animals (P < 0.001). Angiotensin II was 2.4-fold higher in diabetic animals (P = 0.017). Compared with people without DKD, those with DKD had higher urine AOG (170 vs. 15 μg/g) and CTSD (147 vs. 31 μg/g). In people with DKD, urine ACE concentration was 1.8-fold higher (1.4 vs. 0.8 μg/g in those without DKD), while its enzymatic activity was 0.6-fold lower (1.0 vs. 1.6 × 109 RFU/g in those without DKD). Lower ACE activity, but not ACE protein concentration, was associated with ACE inhibitor (ACEI) treatment. After adjustment for clinical covariates, AOG, CTSD, ACE concentration, and ACE activity remained associated with DKD. In conclusion, in mice with streptozotocin-induced diabetes and in humans with DKD, urine concentrations and enzymatic activities of several RAS components are concordantly increased, consistent with enhanced RAS activity and greater angiotensin II formation. ACEI use was associated with a specific reduction in urine ACE activity, not ACE protein concentration, suggesting that it may be a marker of exposure to this widely-used therapy.

Sex differences in the aging pattern of renin\u2013angiotensin system serum peptidases

BackgroundSerum peptidases, such as angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (ACE2), neutral endopeptidase (NEP), aminopeptidase N (APN), and aminopeptidase A (APA), are important elements of the renin–angiotensin system (RAS). Dysregulation of these enzymes has been associated with hypertension and cardiovascular risk. In the present study, serum activities of RAS peptidases were analyzed to evaluate the existence of sexual differences, with a possible different pattern in pre- and post-andropausal/post-menopausal participants.MethodsOne hundred and eighteen healthy men and women between 41 and 70 years of age (58 women and 60 men) were recruited to participate in the study. Serum RAS-regulating enzymes were measured by spectrofluorimetry. Enzymatic activity was recorded as units of enzyme per milliliter of serum (U/mL).ResultsSignificantly lower serum APA activity was observed in men with respect to women; no sex differences were detected for ACE, ACE2, NEP, or APN. Significantly lower APA and ACE serum activity were observed in older men compared to older women. In contrast, younger (<55 years) men had significantly higher values of NEP serum activity than younger women. Significantly lower ACE serum activity was detected in older men compared to younger men. In women, significantly higher ACE2 serum activity was observed in older women compared to younger women.ConclusionsThese results suggest a differential effect of aging on the activity of RAS enzymes in men and women, especially with respect to the breakpoint of andropausia/menopausia, on the critical serum enzymatic activities of the RAS, which could correlate with sexual differences in cardiovascular risk.