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Biomolecules May 2024Peptides possessing antihypertensive attributes via inhibiting the angiotensin-converting enzyme (ACE) were derived through the enzymatic degradation of (ribbonfish)...
Peptides possessing antihypertensive attributes via inhibiting the angiotensin-converting enzyme (ACE) were derived through the enzymatic degradation of (ribbonfish) using alkaline protease. The resulting mixture underwent filtration using centrifugation, ultrafiltration tubes, and Sephadex G-25 gels. Peptides exhibiting ACE-inhibitory properties and DPPH free-radical-scavenging abilities were isolated and subsequently purified via LC/MS-MS, leading to the identification of over 100 peptide components. In silico screening yielded five ACE inhibitory peptides: FAGDDAPR, QGPIGPR, IFPRNPP, AGFAGDDAPR, and GPTGPAGPR. Among these, IFPRNPP and AGFAGDDAPR were found to be allergenic, while FAGDDAPRR, QGPIGPR, and GPTGPAGP showed good ACE-inhibitory effects. IC values for the latter peptides were obtained from HUVEC cells: FAGDDAPRR (IC = 262.98 μM), QGPIGPR (IC = 81.09 μM), and GPTGPAGP (IC = 168.11 μM). Peptide constituents derived from ribbonfish proteins effectively modulated ACE activity, thus underscoring their therapeutic potential. Molecular docking and modeling corroborated these findings, emphasizing the utility of functional foods as a promising avenue for the treatment and prevention of hypertension, with potential ancillary health benefits and applications as substitutes for synthetic drugs.
Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Animals; Humans; Peptides; Human Umbilical Vein Endothelial Cells; Peptidyl-Dipeptidase A; Molecular Docking Simulation; Perciformes
PubMed: 38785988
DOI: 10.3390/biom14050581 -
Frontiers in Cardiovascular Medicine 2024Patients with hypertension are at a high risk of atrial fibrillation (AF). Recent research has indicated the varying effects of antihypertensive medications on...
BACKGROUND
Patients with hypertension are at a high risk of atrial fibrillation (AF). Recent research has indicated the varying effects of antihypertensive medications on developing AF.
OBJECTIVES
We investigated the relationship between different types of antihypertensive medications and the risk of AF occurrence.
METHODS
We analyzed data from 113,582 subjects with national health screening examinations between 2009 and 2014. The study population was categorized according to antihypertensive medication type. The primary outcome was the incidence of AF.
RESULTS
Among 113,582 subjects (mean age 59.4 ± 12.0 years, 46.7% men), 93,557 received monotherapy [angiotensin receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACEi), beta-blockers, calcium channel blockers (CCB), or diuretics], while 34,590 received combination therapy (ARB/beta-blockers, ARB/CCB, ARB/diuretics, or ARB/CCB/diuretics). During a mean follow-up duration of 7.6 ± 2.1 years, 3.9% of patients were newly diagnosed with AF. In monotherapy, ACEi and CCB had similar AF risks as ARB, while beta-blockers and diuretics showed higher AF risks than ARB. In combination therapy, ARBs/CCBs and ARBs/diuretics had the lowest AF risk, whereas ARBs/beta-blockers had the highest compared to ARB/CCB. Among the specific ARBs, the AF risk varied insignificantly, except for telmisartan and candesartan.
CONCLUSIONS
In hypertensive patients receiving monotherapy, ACEi and CCB showed a similar AF risk as ARBs, while beta-blockers and diuretics were associated with a higher risk. Among those receiving combination therapy, ARBs/CCBs and ARBs/diuretics had the lowest AF risk, whereas ARBs/beta-blockers showed the highest risk. Various types of ARBs have different associations with AF risk.
PubMed: 38784173
DOI: 10.3389/fcvm.2024.1372505 -
Frontiers in Pharmacology 2024We investigated the effects of the maintenance of angiotensin-converting enzyme inhibitors (ACE inhibitors) the day of the surgery on the incidence of postoperative...
Pre-operative maintenance of angiotensin-converting enzyme inhibitors is not associated with acute kidney injury in cardiac surgery patients with cardio-pulmonary bypass: a propensity-matched multicentric analysis.
We investigated the effects of the maintenance of angiotensin-converting enzyme inhibitors (ACE inhibitors) the day of the surgery on the incidence of postoperative acute kidney injury (AKI) and cardiac events in patients undergoing cardiac surgery. We performed a multicentric observational study with propensity matching on 1,072 patients treated with ACE inhibitors. We collected their baseline demographic data, comorbidities, and operative and postoperative outcomes. AKI was defined by KDIGO (Kidney Disease: Improving Global Outcome). Maintenance of an ACE inhibitor was not associated with an increased risk of AKI (OR: 1.215 (CI:0.657-2.24), = 0.843, 71 patients (25.1%) vs. 68 patients (24%)). Multivariate logistic regression and sensitive analysis did not demonstrate any association between ACE inhibitor maintenance and AKI, following cardiac surgery (OR: 1.03 (CI:0.81-1.3)). No statistically significant difference occurs in terms of incidence of cardiogenic shock (OR: 1.315 (CI:0.620-2.786)), stroke (OR: 3.313 (CI:0.356-27.523)), vasoplegia (OR: 0.741 (CI:0.419-1.319)), postoperative atrial fibrillation (OR: 1.710 (CI:0.936-3.122)), or mortality (OR: 2.989 (CI:0.343-26.034)). ICU and hospital length of stays did not differ (3 [2; 5] vs. 3 [2; 5] days, = 0.963 and 9.5 [8; 12] vs. 10 [8; 14] days, = 0.638). Our study revealed that maintenance of ACE inhibitors on the day of the surgery was not associated with increased postoperative AKI. ACE inhibitor maintenance was also not associated with an increased rate of postoperative major cardiovascular events (arterial hypotension, cardiogenic shock, vasopressors use, stroke and death).
PubMed: 38783960
DOI: 10.3389/fphar.2024.1343647 -
ESC Heart Failure May 2024Reducing sodium intake is necessary for patients with chronic heart failure (CHF). Salt substitutes (saltSubs) have become increasingly popular as recommendations by...
AIMS
Reducing sodium intake is necessary for patients with chronic heart failure (CHF). Salt substitutes (saltSubs) have become increasingly popular as recommendations by healthcare professionals (HCPs) as well as options for patients and their caregivers. However, their consumption is generally potassium based and remains poorly evaluated in CHF management. Their impact on guideline-directed medical therapies (GDMTs) also remains unknown. The primary objective of this study was to provide a description and estimate of HCP recommendations and reported use of saltSubs in France. Secondary objectives were to identify if there was an association between these recommendations by HCPs and the use of GDMTs.
METHODS AND RESULTS
A nationwide, questionnaire-based, cross-sectional, epidemiological study was conducted from September 2020 to July 2021. Data collection included baseline characteristics, the use and recommendations of saltSubs, and the use of GDMTs, which included (i) angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) or angiotensin receptor-neprilysin inhibitors (ARNis), (ii) mineralocorticoid receptor antagonists (MRAs), and/or (iii) beta-blockers (BBs). In total, 13% of HCPs advised saltSubs and 17% of patients and 22% of caregivers reported their consumption. CHF patients advised to take saltSubs did not differ in terms of left ventricular ejection fraction (EF) <40%, ischaemic origin, and New York Heart Association III-IV class, but were more recently hospitalized for acute HF (P = 0.004). HCPs who recommended saltSubs to patients were more likely to advise an anti-diabetic diet (P < 0.001), cholesterol-lowering diet (P < 0.001), and exercise (P = 0.018). In the overall population, ACEi/ARB/ARNi use was less frequent in case of saltSub recommendations (74% vs. 82%, P = 0.012). The concomitant prescription of none, one, two, or three GDMTs was less favourable in case of saltSub recommendations (P = 0.046). There was no significant difference for the presence of MRA (56% vs. 58%) and/or BB (78% vs. 82%). The under-prescription of ACEi/ARB/ARNi was found when patients had EF < 40% (P = 0.029) and/or EF ≥ 40% (P = 0.043). In the subgroup with left ventricular EF ≥ 40%, we found a higher thiazide use (P = 0.014) and a less frequent use of low EF GDMTs (P = 0.044) in case of being recommended saltSubs.
CONCLUSIONS
Beyond the well-established risk for hyperkalaemia, our preliminary results suggest a potentially negative impact of saltSubs on GDMT use, especially for ACEis/ARBs/ARNis in CHF management. saltSub recommendations and their availability from open sale outlets should be considered to avoid possible misuse or deference from GDMTs in the future. Informed advice to consumers should also be considered from HCPs or pharmacists.
PubMed: 38783593
DOI: 10.1002/ehf2.14706 -
ESC Heart Failure May 2024This study aimed to describe baseline characteristics and adherence among patients with transthyretin amyloid cardiomyopathy (ATTR-CM) treated with tafamidis...
AIMS
This study aimed to describe baseline characteristics and adherence among patients with transthyretin amyloid cardiomyopathy (ATTR-CM) treated with tafamidis (VYNDAQEL®) in Japan using the Japanese Medical Data Vision (MDV) database.
METHODS AND RESULTS
This study was a non-interventional, retrospective cohort study of adult (≥18 years old) patients in the Japanese MDV claims database diagnosed with ATTR-CM and with at least two tafamidis prescriptions of dose strength 4 × 20 mg/day between 1 March 2019 and 31 August 2021. The date of the first prescription was defined as the index date, with follow-up time defined as the time between the first and last prescription plus the days' supply from the last refill. Baseline characteristics were assessed during a 12 month pre-index period. Adherence was measured using two metrics: (i) the modified medication possession ratio (mMPR), calculated by taking the sum of days supplied for all fills within the follow-up period, divided by the number of days of follow-up, and reported as a percentage, with patients classified as adherent with an mMPR of ≥80%, and (ii) the proportion of days covered (PDC), calculated by taking the total number of days' supply dispensed during the follow-up period divided by the number of days of follow-up, adjusting for any days' supply overlap. A total of 210 patients were identified; the mean (standard deviation) age of the cohort was 77 (5.9) years, and the majority (89%) were male. The most common baseline cardiovascular comorbidities were heart failure (85%), ischaemic heart disease (66%), hypertensive diseases (49%), and diabetes (35%); 75% of patients received heart failure medications in the 12 months prior to index, with the most common being beta-blockers (49%), diuretics (48%), angiotensin receptor blockers (30%), angiotensin-converting enzyme inhibitors (22%), and sodium-glucose cotransporter-2 inhibitors (8.1%). Over an average 14 month follow-up, mean mMPR was 96% with a median of 100% [inter-quartile range (IQR): 97-101%]; 93% of patients were adherent (defined as an mMPR ≥ 80%). In the same follow-up period, mean PDC was 93.6% with a median of 99% (IQR: 93-100%). Persistence was high with 78% of patients having a 0 day gap between prescription refills.
CONCLUSIONS
This study found high adherence rates to tafamidis in this real-world Japanese patient population. Adherence rates in this study were similar to those reported by the tafamidis clinical trial and a previously published US commercial claims adherence analysis. Further studies should be conducted to assess the impact of real-world adherence on real-world outcomes.
PubMed: 38783561
DOI: 10.1002/ehf2.14736 -
International Immunopharmacology Jun 2024Activating angiotensin-converting enzyme 2 (ACE2) is an important player in the pathogenesis of septic-related acute respiratory distress syndrome (ARDS). Rosmarinic...
Activating angiotensin-converting enzyme 2 (ACE2) is an important player in the pathogenesis of septic-related acute respiratory distress syndrome (ARDS). Rosmarinic acid (RA) as a prominent polyphenolic secondary metabolite derived from Rosmarinus officinalis modulates ACE2 in sepsis remains unclear, although its impact on ACE inhibition and septic-associated lung injury has been explored. The study investigated the ACE2 expression in lipopolysaccharide (LPS)-induced lungs in mice and BEAS2B cells. Additionally, molecular docking, protein-protein interaction (PPI) network analysis, and western blotting were employed to predict and evaluate the molecular mechanism of RA on LPS-induced ferroptosis in vivo and in vitro. LPS-induced glutathione peroxidase 4 (GPX4) downregulation, ACE/ACE2 imbalance, and alteration of frequency of breathing (BPM), minute volume (MV), and the expiratory flow at 50% expired volume (EF) were reversed by captopril pretreatment in vitro and in vivo. RA notably inhibited the infiltration into the lungs of neutrophils and monocytes with increased amounts of GPX4 and ACE2 proteins, lung function improvement, and decreased inflammatory cytokines levels and ER stress in LPS-induced ARDS in mice. Molecular docking showed RA was able to interact with ACE and ACE2. Moreover, combined with different pharmacological inhibitors to block ACE and ferroptosis, RA still significantly inhibited inflammatory cytokines Interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and C-X-C motif chemokine 2 (CXCL2) levels, as well as improved lung function, and enhanced GPX4 expression. Particularly, the anti-ferroptosis effect of RA in LPS-induced septic ARDS is RAS-dependent.
Topics: Rosmarinic Acid; Animals; Depsides; Ferroptosis; Cinnamates; Respiratory Distress Syndrome; Lipopolysaccharides; Humans; Mice; Male; Sepsis; Angiotensin-Converting Enzyme 2; Molecular Docking Simulation; Peptidyl-Dipeptidase A; Mice, Inbred C57BL; Bronchi; Cell Line; Captopril; Disease Models, Animal; Cytokines
PubMed: 38776851
DOI: 10.1016/j.intimp.2024.112304 -
BMC Cardiovascular Disorders May 2024Acute heart failure is the rapid onset of new or worsening symptoms and signs of heart failure. Despite the increasing burden of heart failure in developing countries... (Observational Study)
Observational Study
BACKGROUND
Acute heart failure is the rapid onset of new or worsening symptoms and signs of heart failure. Despite the increasing burden of heart failure in developing countries like Ethiopia, there is a paucity of comprehensive data regarding the clinical characteristics, treatment patterns, and outcomes of acute heart failure, especially in the selected study area. Therefore, this study aimed to assess the clinical characteristics, treatment patterns, and outcomes of hospitalized patients with acute heart failure at Yekatit 12 Hospital Medical College, Addis Ababa, Ethiopia.
METHODS
This is a retrospective cross-sectional study of 303 acute heart failure patients who were admitted to the medical wards and intensive care unit of Yekatit 12 Hospital Medical College, Addis Ababa, central Ethiopia, from July 1, 2022, to July 1, 2023. A pretested data abstraction format was used for data extraction from electronic medical records, and SPSS version 26 was used for data analysis. Descriptive analysis was used to summarize sociodemographic data, clinical characteristics, treatment patterns, and outcomes of acute heart failure. Bivariate and multivariate logistic regression models were fitted to identify factors associated with in-hospital mortality. The odds ratio (OR) with the corresponding 95% confidence interval (CI) was calculated to show the strength of the association.
RESULTS
Of the 303 patients, 51.5% were females, and the mean age was 56.7 years. The most frequent symptom and sign were dyspnea (98.7%) and peripheral edema (79%), respectively. The commonest underlying cause and precipitating factor of acute heart failure were cor pulmonale (22.8%) and pneumonia (35.3%), respectively. The commonest anti-remodeling medications prescribed on discharge were beta-blockers (47.9%), followed by mineralocorticoid receptor antagonists (42.8%) and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (38.6%), and the least prescribed were sodium-glucose cotransporter 2 inhibitors (8.3%). The in-hospital mortality rate was 8.6%, and the median length of hospital stay was 9 days. Based on the multivariate logistic regression analysis, the most important predictors of in-hospital mortality were systolic blood pressure (SBP) < 115 mmHg (adjusted odds ratio [AOR] = 6.28; 95% CI: 1.99, 19.78), chloride level < 96 mg/dL (AOR = 4.88; 95% CI: 1.30, 18.33), blood urea nitrogen (BUN) > 20 mg/dl (AOR = 5.48; 95% CI: 1.47, 20.49), and presence of dyslipidemia (AOR = 3.73, 95% CI: 1.15, 12.07).
CONCLUSIONS
This study has shown that systolic blood pressure (SBP) < 115 mmHg, blood urea nitrogen (BUN) > 20 mg/dL, chloride (Cl) level < 96 mg/dL, and the presence of dyslipidemia were statistically significant factors associated with in-hospital mortality among patients with acute heart failure. Hence, healthcare providers should stratify patients with acute heart failure upon admission based on their risk of in-hospital mortality and address those potential negative prognostic indicators accordingly.
Topics: Humans; Retrospective Studies; Heart Failure; Ethiopia; Male; Female; Middle Aged; Cross-Sectional Studies; Hospital Mortality; Aged; Acute Disease; Treatment Outcome; Risk Factors; Adult; Risk Assessment; Time Factors; Practice Patterns, Physicians'; Aged, 80 and over; Hospitalization
PubMed: 38773412
DOI: 10.1186/s12872-024-03905-z -
World Journal of Gastroenterology May 2024This editorial contains comments on the article by Zhao in print in the . The mechanisms responsible for hepatic fibrosis are also involved in cancerogenesis. Here, we...
This editorial contains comments on the article by Zhao in print in the . The mechanisms responsible for hepatic fibrosis are also involved in cancerogenesis. Here, we recapitulated the complexity of the renin-angiotensin system, discussed the role of hepatic stellate cell (HSC) autophagy in liver fibrogenesis, and analyzed the possible implications in the development of hepatocarcinoma (HCC). Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers definitively contribute to reducing hepatic fibrogenesis, whereas their involvement in HCC is more evident in experimental conditions than in human studies. Angiotensin-converting enzyme 2 (ACE2), and its product Angiotensin (Ang) 1-7, not only regulate HSC autophagy and liver fibrosis, but they also represent potential targets for unexplored applications in the field of HCC. Finally, ACE2 overexpression inhibits HSC autophagy through the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway. In this case, Ang 1-7 acts binding to the MasR, and its agonists could modulate this pathway. However, since AMPK utilizes different targets to suppress the mTOR downstream complex mTOR complex 1 effectively, we still need to unravel the entire pathway to identify other potential targets for the therapy of fibrosis and liver cancer.
Topics: Humans; TOR Serine-Threonine Kinases; Angiotensin-Converting Enzyme 2; Liver Cirrhosis; AMP-Activated Protein Kinases; Signal Transduction; Autophagy; Hepatic Stellate Cells; Liver Neoplasms; Carcinoma, Hepatocellular; Renin-Angiotensin System; Angiotensin I; Animals; Peptidyl-Dipeptidase A; Angiotensin-Converting Enzyme Inhibitors; Peptide Fragments; Angiotensin Receptor Antagonists; Liver
PubMed: 38764773
DOI: 10.3748/wjg.v30.i18.2391 -
Saudi Journal of Medicine & Medical... 2024Despite guideline recommendations, suboptimal prescription rates of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been...
Prescribing Trends of Renin-Angiotensin System Inhibitors and Mortality among Acute Coronary Syndrome Patients: Insights from the Malaysian National Cardiovascular Disease Registry.
BACKGROUND
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.
OBJECTIVE
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.
METHODOLOGY
This retrospective study utilized data from the Malaysian National Cardiovascular Disease-Acute Coronary Syndrome registry, encompassing consecutive patient records from 2008 to 2017 ( = 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.
RESULTS
The 10-year prescription rate of on-discharge ACEIs/ARBs was 52.8% ( = 32,140), with a significant decline over the years [linear trend test, = 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; < 0.001).
CONCLUSION
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.
PubMed: 38764563
DOI: 10.4103/sjmms.sjmms_422_23 -
Advances and Applications in... 2024This study aimed to screen potential drug candidates from the flavonoids of the genus for the Corona Virus Disease 2019 (COVID-19) treatment.
PURPOSE
This study aimed to screen potential drug candidates from the flavonoids of the genus for the Corona Virus Disease 2019 (COVID-19) treatment.
PATIENTS AND METHODS
A comprehensive screening was conducted on the structures of 473 flavonoids derived from the genus , focusing on their potential toxicity and pharmacokinetic profiles. Subsequently, flavonoids that were non-toxic and possessed favorable pharmacokinetic properties underwent further analysis to explore their interactions with the angiotensin-converting enzyme 2 (ACE2) receptor, employing molecular docking and molecular dynamics simulations.
RESULTS
Among 473 flavonoids, 104 were predicted to be safe from being mutagenic, hepatotoxic, and inhibitors of the human ether-a-go-go-related gene (hERG). Among these 104 flavonoids, 18 compounds were predicted not to be substrates of P-glycoprotein (P-gp). Among these 18 flavonoids, gangetinin () and erybraedin D () exhibit low binding affinities and root mean square deviation (RMSD) values, indicating stable binding to the ACE2 receptor. The physicochemical attributes of compounds 310 and 471 suggest that they possess drug-like properties.
CONCLUSION
Gangetinin () and erybraedin D () may serve as promising candidates for COVID-19 treatment due to their potential to inhibit the ACE2-RBD interaction. This warrants further investigation into their inhibitory effects on ACE2-RBD binding through in vitro experiments.
PubMed: 38764460
DOI: 10.2147/AABC.S454961