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Cureus Dec 2023The growing research regarding the implementation of angiotensin-converting enzyme-2 inhibitors (ACEi) and angiotensin receptor blockers (ARBs) in the treatment of... (Review)
Review
Clinical Outcomes of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in COVID-19 Patients With Pre-existing Cardiac Comorbidities: A Literature Review.
The growing research regarding the implementation of angiotensin-converting enzyme-2 inhibitors (ACEi) and angiotensin receptor blockers (ARBs) in the treatment of COVID-19 in patients with pre-existing cardiac comorbidities has become a large topic of discussion since the onset of the pandemic. Previous research primarily associates positive outcomes to the use of these drug classes due to their mechanism of action, which involves the downregulation of angiotensin I-converting enzyme 2 (ACE2) in the renin-angiotensin-aldosterone-system (RAAS) pathway, inflammatory mediators, and cytokines. Thus, these medications can convey preventative and protective effects in patients suffering from a SARS-CoV-2 infection. While we explored the studies that supported the positive outcomes of the use of these drugs in the first half of this review, we also expanded on the limitations of these studies in the latter portion. We also further explored the contradictory studies that indicated that using these antihypertensives can paradoxically increase the severity of COVID-19 infection as well. The studies in support of the use of these medications should consider epigenetic variations, ACE2 variants and acknowledge inherent genetic variations in certain ethnic groups as some have a predisposition for a severe COVID-19 infection. Additionally, mortality rates need to be taken into consideration in these studies as they naturally differ throughout the trajectory of the COVID-19 pandemic. While some studies are in support of the use of these antihypertensives despite other studies suggesting otherwise, further research is needed to explore the long-term effects of these antihypertensives and observe whether they are truly beneficial or not in reducing the severity of COVID-19 infections.
PubMed: 38283421
DOI: 10.7759/cureus.51244 -
The Journal of General and Applied... Jan 2024To enhance the value of surimi, efforts have been made to develop a fermentation method with lactic acid bacteria (LAB) to proteolyze fish protein. However, fermenting...
To enhance the value of surimi, efforts have been made to develop a fermentation method with lactic acid bacteria (LAB) to proteolyze fish protein. However, fermenting unheated surimi poses a spoilage risk due to its high bacterial content. Surimi heat treatment can prevent spoilage, but gel formation induced by heating introduces another technical issue: it hinders uniform fermentation. Thus, this study aims to observe the proteolysis and enhance the functionality of seafood product through lactic acid fermentation of kamaboko, a heated surimi. Upon analyzing the kamaboko fermented with Lactobacillus helveticus JCM1004, we observed that LAB produced protease, resulting in the degradation of myosin heavy chain and actin during fermentation. Lactic acid fermentation significantly augmented the peptide content of kamaboko, subsequently elevating the angiotensin Ⅰ-converting enzyme (ACE) inhibitory activity in 200-fold diluted extract of fermented kamaboko to approximately 70% and higher. Notably, our investigation revealed that proteolysis was confined to the surface of kamaboko, as evidenced by SDS-PAGE analysis. This observation implies that the surface area of kamaboko influences the ACE inhibitory activity. Through a comparative analysis of various bacterial strains, we demonstrated that the increase in ACE inhibitory activity is contingent on the protease generated by LAB. These results suggest that LAB-mediated proteolysis of fish proteins liberates bioactive peptides, thereby manifesting in the ACE inhibitory activity. In summary, this study underscores that the fermentation of kamaboko employing proteolytic LAB holds promise in the development of novel functional seafood products.
PubMed: 38281752
DOI: 10.2323/jgam.2024.01.003 -
Frontiers in Endocrinology 2023Twin gestation is related to a higher risk of hypertensive disorders in pregnancy with possible risk stratification depending on chorionicity. It may be related to... (Observational Study)
Observational Study
INTRODUCTION
Twin gestation is related to a higher risk of hypertensive disorders in pregnancy with possible risk stratification depending on chorionicity. It may be related to differences in plasma renin-angiotensin-aldosterone components between monochorionic and dichorionic twin pregnancies. The study aimed to analyze the plasma ANG II and ANG 1-7 concentrations in women with monochorionic and dichorionic twin gestation.
METHODS
A prospective observational study included 79 women between 32 and 34 weeks of gestation with twin pregnancy (31 with monochorionic gestation and 48 with dichorionic gestation). Angiotensin II and angiotensin 1-7 concentrations were measured in the collected blood samples.
RESULTS
No significant differences were observed in angiotensin II concentrations between the dichorionic and monochorionic group with significantly higher levels of angiotensin 1-7 being observed in the dichorionic group. Angiotensin 1-7 level was higher than angiotensin II in 20 women (64.5%) in the monochorionic group and in 42 women (87.5%, p=0.01) in the dichorionic group. Higher plasma concentrations of angiotensin II and lower concentrations of angiotensin 1-7 were found in 5 women with gestational hypertension and in 3 with preeclampsia compared to normotensive women.
DISCUSSION
It is the first study investigating angiotensin II and angiotensin 1-7 in twin pregnancies regarding chorionicity. Our results showed that plasma angiotensin 1-7 concentration was related to chorionicity, while plasma angiotensin II level was not. In most women with twin gestation angiotensin 1-7 concentration exceeded the concentration of angiotensin II. A switch in the relation between angiotensin II and angiotensin 1-7 was observed in hypertensive pregnant women.
Topics: Pregnancy; Female; Humans; Pregnancy, Twin; Angiotensin II; Pregnancy Trimester, Third; Peptide Hormones; Hypertension, Pregnancy-Induced; Angiotensin I; Peptide Fragments
PubMed: 38260128
DOI: 10.3389/fendo.2023.1329025 -
Biomedicines Jan 2024We hypothesized that subjects with heterozygous loss-of-function (LoF) mutations are at risk for Alzheimer's disease because amyloid Aβ42, a primary component of the...
We hypothesized that subjects with heterozygous loss-of-function (LoF) mutations are at risk for Alzheimer's disease because amyloid Aβ42, a primary component of the protein aggregates that accumulate in the brains of AD patients, is cleaved by ACE (angiotensin I-converting enzyme). Thus, decreased ACE activity in the brain, either due to genetic mutation or the effects of ACE inhibitors, could be a risk factor for AD. To explore this hypothesis in the current study, existing SNP databases were analyzed for LoF mutations using four predicting tools, including PolyPhen-2, and compared with the topology of known mutations already associated with AD. The combined frequency of >400 of these LoF-damaging mutations in the general population is quite significant-up to 5%-comparable to the frequency of AD in the population > 70 y.o., which indicates that the contribution of low ACE in the development of AD could be under appreciated. Our analysis suggests several mechanisms by which ACE mutations may be associated with Alzheimer's disease. Systematic analysis of blood ACE levels in patients with all mutations is likely to have clinical significance because available sequencing data will help detect persons with increased risk of late-onset Alzheimer's disease. Patients with transport-deficient mutations (about 20% of damaging ACE mutations) may benefit from preventive or therapeutic treatment with a combination of chemical and pharmacological (e.g., centrally acting ACE inhibitors) chaperones and proteosome inhibitors to restore impaired surface ACE expression, as was shown previously by our group for another transport-deficient ACE mutation-Q1069R.
PubMed: 38255267
DOI: 10.3390/biomedicines12010162 -
International Journal of Molecular... Dec 2023Diabetic nephropathy (DN) is a crucial metabolic health problem. The renin-angiotensin system (RAS) is well known to play an important role in DN. Abnormal RAS activity...
Studying the Roles of the Renin-Angiotensin System in Accelerating the Disease of High-Fat-Diet-Induced Diabetic Nephropathy in a db/db and ACE2 Double-Gene-Knockout Mouse Model.
Diabetic nephropathy (DN) is a crucial metabolic health problem. The renin-angiotensin system (RAS) is well known to play an important role in DN. Abnormal RAS activity can cause the over-accumulation of angiotensin II (Ang II). Angiotensin-converting enzyme inhibitor (ACEI) administration has been proposed as a therapy, but previous studies have also indicated that chymase, the enzyme that hydrolyzes angiotensin I to Ang II in an ACE-independent pathway, may play an important role in the progression of DN. Therefore, this study established a model of severe DN progression in a db/db and ACE2 KO mouse model (db and ACE2 double-gene-knockout mice) to explore the roles of RAS factors in DNA and changes in their activity after short-term (only 4 weeks) feeding of a high-fat diet (HFD) to 8-week-old mice. The results indicate that FD-fed db/db and ACE2 KO mice fed an HFD represent a good model for investigating the role of RAS in DN. An HFD promotes the activation of MAPK, including p-JNK and p-p38, as well as the RAS signaling pathway, leading to renal damage in mice. Blocking Ang II/AT1R could alleviate the progression of DN after administration of ACEI or chymase inhibitor (CI). Both ACE and chymase are highly involved in Ang II generation in HFD-induced DN; therefore, ACEI and CI are potential treatments for DN.
Topics: Animals; Mice; Angiotensin II; Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Antiviral Agents; Chymases; Diabetes Mellitus; Diabetic Nephropathies; Diet, High-Fat; Disease Models, Animal; Mice, Knockout; Peptide Hormones; Renin-Angiotensin System; Serine Proteases
PubMed: 38203500
DOI: 10.3390/ijms25010329 -
ACS Omega Dec 2023Macroalgal proteins were extracted from (URPE) (green), (PPPE) (brown), and (LOPE) (red) using ultrasound-assisted enzymatic extraction, which is one of the green...
Macroalgal proteins were extracted from (URPE) (green), (PPPE) (brown), and (LOPE) (red) using ultrasound-assisted enzymatic extraction, which is one of the green extraction technologies. Techno-functional, characteristic, and digestibility properties, and biological activities including antioxidant (AOA) and angiotensin-I converting enzyme (ACE-I) inhibitory activities were also investigated. According to the results, the extraction yield (EY) (94.74%) was detected in the extraction of , followed by and . PPPE showed the highest ACE-I inhibitory activity before digestion. In contrast to PPPE, LOPE (20.90 ± 0.00%) and URPE (20.20 ± 0.00%) showed higher ACE-I inhibitory activity after digestion. The highest total phenolic content (TPC) (77.86 ± 1.00 mg GAE/g) was determined in LOPE. On the other hand, the highest AOA (74.69 ± 1.78 mg TE/g) and AOA (251.29 ± 5.0 mg TE/g) were detected in PPPE. After digestion, LOPE had the highest TPC (22.11 ± 2.18 mg GAE/g), AOA (8.41 ± 0.06 mg TE/g), and AOA (88.32 ± 0.65 mg TE/g) ( < 0.05). protein digestibility of three macroalgal protein extracts ranged from 84.35 ± 2.01% to 94.09 ± 0.00% ( < 0.05). Three macroalgae showed high oil holding capacity (OHC), especially PPPE (410.13 ± 16.37%) ( < 0.05), but they showed minimum foaming and emulsifying properties. The quality of the extracted macroalgal proteins was assessed using FTIR, SDS-PAGE, and DSC analyses. According to our findings, the method applied for macroalgal protein extraction could have a potential the promise of ultrasonication application as an environmentally friendly technology for food industry. Moreover, URPE, PPPE, and LOPE from sustainable sources may be attractive in terms of nourishment for people because of their digestibility, antioxidant properties, and ACE-I inhibitory activities.
PubMed: 38162757
DOI: 10.1021/acsomega.3c05041 -
Naunyn-Schmiedeberg's Archives of... Jul 2024Systemic vascular endothelial growth factor (VEGF) blockade has been the top adjunctive chemotherapy since 1990. Anti-VEGF therapy has also been associated with worsened...
Systemic vascular endothelial growth factor (VEGF) blockade has been the top adjunctive chemotherapy since 1990. Anti-VEGF therapy has also been associated with worsened renal function in some patients. However, the association between patient outcomes and use of intravitreal VEGF inhibitors remains controversial. Thus, it is necessary to determine the action mechanism and long-term renal effects of ranibizumab. The National Health Insurance Research Database (NHIRD) is one of the largest global databases that are extensively used for epidemiological research. NHIRD contains the medical information of all insureds, such as inpatient, outpatient, emergency, and traditional Chinese medicine records. We selected subjects aged ≥ 20 years who recently administered ranibizumab for the ranibizumab cohort. Non-ranibizumab cohort consisted of subjects who did not receive ranibizumab, and the index date was a random date between 2008 and 2018. We excluded subjects with missing sex and age records and those in which the date of primary outcome was before the index date. The two cohorts were matched via 1:1 propensity score matching based on sex, age, index year, hypertension, diabetes mellitus, hyperlipidemia, stroke, coronary artery disease, alcoholism, chronic obstructive pulmonary disease, and age-related macular degeneration, retinal vein occlusion, and diabetic macular edema. Medical confounders were angiotensin I-converting enzyme inhibitors, statins, corticosteroids, VEGF inhibitors including bevacizumab and aflibercept, lithium, amphotericin B, adefovir, NSAIDS, cisplatin, and calcineurin inhibitors. Among 48,248 participants aged ≥ 20 years, 24,136 (50%) received ranibizumab (13,565 male [56.20%] and 10,571 female [43.80%]). Moreover, 24,136 participants who did not receive ranibizumab were matched by age, sex, comorbidities, and medications. Subjects who received ranibizumab exhibited a significantly higher risk of CKD than those who did not receive ranibizumab (adjusted hazard ratio = 1.88, 95% CI = 1.79-1.96). Our findings revealed that exposure to intravitreal ranibizumab is an independent risk factor for CKD. Therefore, physicians and ophthalmologists should make the patients aware of such a correlation to increase patient safety and decrease the CKD burden.
Topics: Humans; Male; Female; Taiwan; Middle Aged; Ranibizumab; Renal Insufficiency, Chronic; Aged; Intravitreal Injections; Angiogenesis Inhibitors; Adult; Risk Factors; Databases, Factual; Cohort Studies; Vascular Endothelial Growth Factor A; Retrospective Studies
PubMed: 38153512
DOI: 10.1007/s00210-023-02910-x -
International Journal of Molecular... Dec 2023Pulmonary arterial hypertension (PAH) is a debilitating progressive disease characterized by excessive pulmonary vasoconstriction and abnormal vascular remodeling...
Pulmonary arterial hypertension (PAH) is a debilitating progressive disease characterized by excessive pulmonary vasoconstriction and abnormal vascular remodeling processes that lead to right-ventricular heart failure and, ultimately, death. Although our understanding of its pathophysiology has advanced and several treatment modalities are currently available for the management of PAH patients, none are curative and the prognosis remains poor. Therefore, further research is required to decipher the molecular mechanisms associated with PAH. Angiotensin-converting enzyme 2 (ACE2) plays an important role through its vasoprotective functions in cardiopulmonary homeostasis, and accumulating preclinical and clinical evidence shows that the upregulation of the ACE2/Angiotensin-(1-7)/MAS1 proto-oncogene, G protein-coupled receptor (Mas 1 receptor) signaling axis is implicated in the pathophysiology of PAH. Herein, we highlight the molecular mechanisms of ACE2 signaling in PAH and discuss its potential as a therapeutic target.
Topics: Humans; Pulmonary Arterial Hypertension; Angiotensin-Converting Enzyme 2; Hypertension, Pulmonary; Peptidyl-Dipeptidase A; Familial Primary Pulmonary Hypertension; Receptors, G-Protein-Coupled; Angiotensin I; Peptide Fragments; Renin-Angiotensin System
PubMed: 38139269
DOI: 10.3390/ijms242417441 -
Royal Society Open Science Dec 2023Two bisoprolol derivatives, -acetyl bisoprolol and -formyl bisoprolol, belonging to the beta-blocker class of antihypertensive drugs, were synthesized using acetylation...
Two bisoprolol derivatives, -acetyl bisoprolol and -formyl bisoprolol, belonging to the beta-blocker class of antihypertensive drugs, were synthesized using acetylation and formylation reactions. The yields of the reactions were determined to be 32.40% for -acetyl bisoprolol and 20.20% for -formyl bisoprolol. methods such as molecular docking, molecular dynamics simulation and SwissADME prediction were employed to evaluate the potential of these bisoprolol derivatives as antihypertensive drugs. These methods were used to assess the interaction between the bisoprolol derivatives and various receptors associated with hypertension, including human angiotensin I-converting enzyme (PDB ID: 1O8A), renin (PDB ID: 2V0Z), beta-1 adrenergic receptors (PDB ID: 4BVN, 7BVQ), voltage-dependent L-type calcium channel subunit alpha-1S (PDB ID: 6JP5) and mineralocorticoid receptor (PDB ID: 6L88). Our results demonstrated the highest binding energy when bisoprolol and its derivatives bound to 4BVN, with binding energy values of 6.74 kcal mol, 7.03 kcal mol and 7.63 kcal mol for bisoprolol, -acetyl bisoprolol and -formyl bisoprolol, respectively. The stability of these complexes was confirmed by molecular dynamics simulations, with a root-mean-square deviation value of approximately 2. Furthermore, the SwissADME results indicated that both derivatives exhibited similar properties to the reference drug bisoprolol.
PubMed: 38126063
DOI: 10.1098/rsos.231112