UNASSIGNED: Non-ischemic dilated cardiomyopathy (NIDCM) is a form of heart failure with a poor prognosis and unclear optimal management. The aim of the study was to systematically review the literature and assess the efficacy and safety of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors in the management of chronic heart failure secondary to NIDCM and explore their putative mechanisms of action.
UNASSIGNED: Studies from 1990 to 2023 were reviewed using PubMed and EMBASE, focusing on their effects on left ventricular ejection fraction (LVEF) in NIDCM patients, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
UNASSIGNED: Beta-blockers showed a significant beneficial effect on LVEF improvement in NIDCM, with an overall effect size of Cohen\'s d = 1.30, 95% confidence interval (CI) (0.76, 1.84), high heterogeneity (Tau2 = 0.90; Chi2 = 162.05, df = 13, P < 0.00001; I2 = 92%), and a significant overall effect (Z = 4.72, P < 0.00001). ACE inhibitors also showed a beneficial role, but with less heterogeneity (Tau2 = 0.02; Chi2 = 1.09, df = 1, P = 0.30; I2 = 8%) and a nonsignificant overall effect (Z = 1.36, P = 0.17), 95% CI (-0.24, 1.31).
UNASSIGNED: The study highlights the efficacy of carvedilol in improving LVEF in NIDCM patients over ACE inhibitors, recommends beta-blockers as first-line therapy, and advocates further research on ACE inhibitors.

A two-year-old male veiled chameleon (Chamaeleo calyptratus) was referred for a gular oedema and bilateral blepharoedema. The echocardiography revealed a ventricular hypertrophy, pericardial effusion, and valvular regurgitation of the right atrioventricular valve. Treatment with hydrochlorothiazide, enalapril, and carvedilol was commenced. Within 3 weeks of treatment, the valvular regurgitation was noticeably decreased. In the 4th week of treatment, the echocardiography revealed a reduction in the myocardium hypertrophy. After an additional month of home treatment, the patient was presented with anorexia and decreased activity. Despite the supportive care, the patient died. The histopathology revealed mild to moderate fibrosis of the epicardium. Moderate to severe fibrosis, degeneration of the myofibrils, fatty atrophy, interstitial oedema and mild calcification was seen in the atria. The tunica intima, media and adventitia of the major cardiac vessels were moderately fibrotic, swollen and interfused by myxoedema. The kidney histopathology revealed moderate sclerosis and atrophy of the glomeruli, vacuolation of the tubular epithelium, fibrosis, and infiltration of the leucocytes in the interstitium. The therapeutic protocol with hydrochlorothiazide, ACE inhibitor enalapril and β-blocker carvedilol reduced the myocardium hypertrophy and the valvular regurgitation; however, the prolonged use of diuretics jeopardized the renal function in our patient. Frequent blood analyses are necessary using diuretics in reptile patients.

Angiotensin converting enzyme (ACE) exerts strong modulation of myeloid cell function independently of its cardiovascular arm. The success of the ACE-overexpressing murine macrophage model, ACE 10/10, in treating microbial infections and cancer opens a new avenue into whether ACE overexpression in human macrophages shares these benefits. Additionally, as ACE inhibitors are a widely used antihypertensive medication, their impact on ACE expressing immune cells is of interest and currently understudied. In the present study, we utilized mass spectrometry to characterize and assess global proteomic changes in an ACE-overexpressing human THP-1 cell line. Additionally, proteomic changes and cellular uptake following treatment with an ACE C-domain selective inhibitor, lisinopril-tryptophan, were also assessed. ACE activity was significantly reduced following inhibitor treatment, despite limited uptake within the cell, and both RNA processing and immune pathways were significantly dysregulated with treatment. Also present were upregulated energy and TCA cycle proteins and dysregulated cytokine and interleukin signaling proteins with ACE overexpression. A novel, functionally enriched immune pathway that appeared both with ACE overexpression and inhibitor treatment was neutrophil degranulation. ACE overexpression within human macrophages showed similarities with ACE 10/10 murine macrophages, paving the way for mechanistic studies aimed at understanding the altered immune function.

The renin-angiotensin system (RAS) is known to affect diverse physiological processes that affect the functioning of many key organs. Angiotensin-converting enzyme (ACE) modulates a variety of bioactive peptides associated with pain. ACE inhibitors (ACEis) have found applications in the treatment of cardiovascular, kidney, neurological and metabolic disorders. However, ACEis also tend to display undesirable effects, resulting in increased pain sensitization and mechanical allodynia. In this review, we provide comprehensive discussion of preclinical and clinical studies involving the evaluation of various clinically approved ACEis. With the emerging knowledge of additional factors involved in RAS signaling and the indistinct pharmacological role of ACE substrates in pain, extensive studies are still required to elucidate the mechanistic role of ACE in pain perception.

Inhibition of ACE is considered as one of the main strategies to reduce hypertension. ACE inhibitors derived from Suaeda salsa (S. salsa) present a novel antihypertensive agent source. This study employed 3D-QSAR pharmacophore, metabolomics, docking-based screening, and molecular dynamics simulations to identify ACE inhibitors from S. salsa. A set of 53 known molecules was chemically diverse to construct a 3D-QSAR model for predictive purposes. S. salsa was characterized using UPLC-QqQ-MS/MS and UPLC-Q-TOF-LC-MS techniques, 211 and 586 kinds of bioactive metabolites were identified, respectively. A total of 680 compounds were collected for database construction and virtual screening. An ADMET assessment was conducted to evaluate drug-likeness and pharmacokinetics parameters. Moreover, molecular docking results show that six top hit compounds bind to ACE tightly. Specially, diosmin could interact with ACE by hydrogen bond, Pi-cation bond, and metal bond. Molecular dynamics (MD) simulation and MMPBSA calculations were subsequently employed to elucidate complex stability and the interaction between diosmin and ACE, indicating it a strong ACE inhibitory activity. In conclusion, this study suggests that S.salsa represents a potential source of antihypertensive agents.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s40203-024-00233-0.

UNASSIGNED: Despite guideline recommendations, suboptimal prescription rates of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been observed in patients with acute coronary syndrome.
UNASSIGNED: This study aimed to examine the temporal trends, variations, and mortality outcomes among acute coronary syndrome patients prescribed ACEIs/ARBs in the multi-ethnic population of Malaysia.
UNASSIGNED: This retrospective study utilized data from the Malaysian National Cardiovascular Disease-Acute Coronary Syndrome registry, encompassing consecutive patient records from 2008 to 2017 (N = 60,854). Ten-year temporal trends of on-discharge ACEIs/ARBs prescription were examined. Demographics, clinical characteristics and 1-year all-cause mortality outcomes were compared between patients prescribed and not prescribed ACEIs/ARBs.
UNASSIGNED: The 10-year prescription rate of on-discharge ACEIs/ARBs was 52.8% (n = 32,140), with a significant decline over the years [linear trend test, P = 0.008; SD = 0.03; SE = 0.001; 95% CI = 0.55-0.64]. Patients aged ≥65 years (aOR = 0.79; 95% CI = 0.73-0.86) were less likely to be prescribed ACEIs/ARBs than those aged <65 years. In addition, patients with comorbid diabetes mellitus (DM) (aOR = 0.85; 95% CI = 0.79-0.92) and chronic kidney disease (CKD) (aOR = 0.34; 95% CI = 0.30-0.40) were significantly less likely to receive ACEIs/ARBs. IPW-adjusted survival analysis revealed a 38% lower 1-year all-cause mortality rate in patients prescribed on-discharge ACEIs/ARBs (HR = 0.62; 95% CI = 0.56-0.69; P < 0.001).
UNASSIGNED: Acute coronary syndrome patients with concomitant DM and CKD were less likely to receive on-discharge ACEIs/ARBs in Malaysia. Suboptimal prescription rates of ACEIs/ARBs persisted over the 10-year period, despite improved 1-year survival in ACS patients prescribed ACEIs/ARBs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, uses the surface angiotensin-converting enzyme 2 (ACE2) receptor as the site of entry into host cardiac, respiratory, intestinal, renal, and nervous system cells. Predisposing risk factors such as cardiovascular disease increase the risk of developing severe disease. Hypertension is characterized by the stimulation of the renin-angiotensin-aldosterone system (RAAS). Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin 2 receptor blockers (ARBs), medications used to treat hypertension, inhibit RAAS and its downstream effects; however, they have also been shown to upregulate ACE2 receptors. In this review, we aim to evaluate the effectiveness of ACEi/ARBs as an adjunct therapy in patients with SARS-CoV-2 as well as examine the possible protective effects and impact on infection rate and disease severity. A PubMed literature search excluding sources outside the United States and duplicates was performed using the following search criteria: \"COVID-19 AND cardiovascular disease AND ACEi AND ARB\", \"SARS-COVID-19 OR COVID-19, AND ACEi AND ARB AND Infection rate\", \"COVID-19 AND ACEi and ARB\", \"Omicron BA.1 and BA.2 AND ACE2 OR ARBs\", \"Omicron AND ACEi AND ARBs\". This resulted in 33 final sources. The review concluded that ACEi/ARB therapy may continue to improve COVID-19 survival as previous treatment is associated with positive clinical outcomes. Patients taking ACEis or ARBs were found to have a decreased risk of hospitalization, reduced severity of COVID-19 pneumonia, a lesser need for mechanical ventilation, and an overall reduction in mortality rate. No statistically significant association between ACEi/ARB use and enhanced COVID-19 infectivity was found. The Omicron variant is theoretically more infectious and was associated with increased negative clinical outcomes in those undertreated with ACEis/ARBs. The majority of the literature supports the current guidelines from the American College of Cardiology (ACC), American Heart Association (AHA), European Society of Cardiology (ESC), and Heart Failure Society of America (HFSA), which state that ACEi and ARB medications should not be withdrawn from or initiated on patients with cardiovascular disease who are infected with SARS-CoV-2. More research needs to be conducted on the association between the emerging COVID-19 variants and ACEis/ARBs to give clinicians confidence when treating patients within this subgroup of the population.

BACKGROUND: Angiotensin-converting enzyme (ACE) is responsible for the production of angiotensin II, and increased production of angiotensin II is observed in diabetes. What is more, ACE polymorphisms may play a role in the development of diabetic nephropathy. The aim of this study was to assess the role of selected ACE polymorphisms (rs4343 and rs4646994) in the risk of development of diabetic nephropathy and in the likelihood of renal replacement therapy.
METHODS: ACE polymorphisms were analyzed in a group of 225 patients who were divided into three subgroups. The rs4343 polymorphism was determined using the PCR-RFLP, and the rs4646994 polymorphism was determined using the PCR. Molecular docking between domains of ACE and its ligands was performed by using AutoDock Vina.
RESULTS: The G/G genotype of rs4343 polymorphism is associated with increased odds of developing diabetic nephropathy. The G allele is also associated with a higher risk of this disease. Similar results were obtained in patients who had already had a kidney transplant as a result of diabetic nephropathy.
CONCLUSIONS: The presence of G/G and G/A genotypes, and the G allele increases the likelihood of developing diabetic nephropathy. This may also be a risk factor for renal replacement therapy.

Stevens-Johnson syndrome (SJS) is a severe and potentially debilitating skin reaction frequently related to medication use. Allopurinol and angiotensin-converting enzyme (ACE) inhibitors are commonly prescribed medications for prevalent health conditions worldwide, and their interaction associated with SJS warrants further investigation. A comprehensive literature search was performed to investigate cases as studies related to SJS occurring in patients with concomitant use of allopurinol and ACE inhibitors. We identified case reports and studies detailing hypersensitivity reactions, including SJS, attributed to a combination of allopurinol and ACE inhibitors. Despite the drug-drug interactions or lack thereof seen in patient populations, there is no definitive evidence of a pharmacokinetic interaction between allopurinol and ACE inhibitors. We were only able to find one case report specifically detailing SJS in a patient on combined ACE inhibitors and allopurinol. While the exact mechanism of the interaction is unclear, those reported cases of severe hypersensitivity reactions suggest a previous history of impaired renal function as a predisposing factor in the development of SJS. The potential risk of SJS with coadministration of ACE inhibitors and allopurinol is a drug-drug interaction that physicians should be aware of. This topic requires additional attention to determine if this drug combination should be avoided entirely in certain patients.

UNASSIGNED: To assess the characteristics of patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mid-range ejection fraction (HFmrEF), as well as the current application of guideline-directed medical therapy (GDMT) in Palestine.
UNASSIGNED: This retrospective cohort study involved a population of heart failure (HF) patients who visited cardiology clinics at An-Najah National University Hospital and the National Hospital, Palestine. The primary outcome measures of interest were the proportions of patients prescribed guideline-based cardiovascular medications (GBCMs), such as angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs), β-blockers, and mineralocorticoid receptor antagonists (MRAs), and the corresponding optimized doses at ≥ 50 % of targets and the reasons underlying the non-prescription of GDMT.
UNASSIGNED: A total of 70.5%, 56.6%, and 88.6% of patients were on ACEIs/ARBs, MRAs, and β-blockers, respectively. Of all patients, 38.7% were on the triple GDMT regimen.
UNASSIGNED: Less than half the patients received the triple combination treatment. Age, diabetes mellitus, chronic renal disease, and admission to the hospital for HF all had significant independent relationships with the reduced utilization and inadequate dosage of GDMT.