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Molecules (Basel, Switzerland) Aug 2023This research aimed to determine the biofunctional properties of wheat flour (WF) protein fractions and modifications to the antioxidant, anti-α-amylase and...
Functional and Bioactive Properties of Wheat Protein Fractions: Impact of Digestive Enzymes on Antioxidant, α-Amylase, and Angiotensin-Converting Enzyme Inhibition Potential.
This research aimed to determine the biofunctional properties of wheat flour (WF) protein fractions and modifications to the antioxidant, anti-α-amylase and anti-angiotensin-I converting enzyme (ACE) activities induced by the action of digestive endopeptidases in vitro. A molecular characterization of the most abundant protein fractions, i.e., albumins, glutelins-1, glutelins-2 and prolamins, showed that low- and high-MW polypeptides rich in cysteine, glutamic acid and leucine were present in albumins and glutelins, whereas low-MW subunits with a high proportion of polar amino acids prevailed in prolamins. Prolamins exhibited the second-highest water holding capacity (54%) after WF (84%), while albumins provided superior foam stability (76%). Prolamins, glutenins-1 and globulins demonstrated the highest antioxidant activity (up to 95%, 68% and 59%, respectively) both before and after hydrolysis with pepsin (P-H) or trypsin-chymotrypsin (TC-H). Prolamins, globulins and WF strongly inhibited α-amylase (>90%) before and after TC-H, and before P-H (55-71%). Moreover, P-H significantly increased α-amylase inhibition by albumins from 53 to 74%. The fractions with strong ACE inhibitory activity (70-89%) included prolamins and globulins after TC-H or P-H, as well as globulins before TC-H and WF before P-H. This novel evidence indicates that WF protein fractions and their peptide-enriched P and TC hydrolysates are excellent sources of multifunctional bioactives with antioxidant, antihyperglycemic and antihypertensive potential.
Topics: Antioxidants; Triticum; alpha-Amylases; Flour; Albumins; Glutens; Gastrointestinal Agents
PubMed: 37630264
DOI: 10.3390/molecules28166012 -
American Journal of Physiology. Cell... Apr 2024Cardiometabolic diseases are often associated with heightened levels of angiotensin II (Ang II), which accounts for the observed oxidative stress, inflammation, and...
Cardiometabolic diseases are often associated with heightened levels of angiotensin II (Ang II), which accounts for the observed oxidative stress, inflammation, and fibrosis. Accumulating evidence indicates a parallel upregulation of dipeptidyl dipeptidase 4 (DPP4) activity in cardiometabolic diseases, with its inhibition shown to mitigate oxidative stress, inflammation, and fibrosis. These findings highlight an overlap between the pathophysiological mechanisms used by Ang II and DPP4. Recent evidence demonstrates that targeted inhibition of DPP4 prevents the rise in Ang II and its associated molecules in experimental models of cardiometabolic diseases. Similarly, inhibitors of the angiotensin I-converting enzyme (ACE) or Ang II type 1 receptor (AT1R) blockers downregulate DPP4 activity, establishing a bidirectional relationship between DPP4 and Ang II. Here, we discuss the current evidence supporting the cross talk between Ang II and DPP4, along with the potential mechanisms promoting this cross regulation. A comprehensive analysis of this bidirectional relationship across tissues will advance our understanding of how DPP4 and Ang II collectively promote the development and progression of cardiometabolic diseases.
Topics: Humans; Angiotensin II; Dipeptidyl Peptidase 4; Peptidyl-Dipeptidase A; Receptor, Angiotensin, Type 1; Inflammation; Fibrosis; Cardiovascular Diseases; Angiotensin I
PubMed: 38581656
DOI: 10.1152/ajpcell.00734.2023 -
Journal of the... 2023All strains of SARS-CoV-2, as well as previously described SARS-CoV and MERS-CoV, bind to ACE2, the cell membrane receptor of -coronaviruses. Monocarboxypeptidase ACE2... (Review)
Review
All strains of SARS-CoV-2, as well as previously described SARS-CoV and MERS-CoV, bind to ACE2, the cell membrane receptor of -coronaviruses. Monocarboxypeptidase ACE2 activity stops upon viral entry into cells, leading to inadequate tissue production of angiotensin 1-7 (Ang1-7). Acute lung injury due to the human respiratory syncytial virus (hRSV) or avian influenza A H7N9 and H5N1 viruses is also characterized by significant downregulation of lung ACE2 and increased systemic levels of angiotensin II (Ang II). Restoration of Ang1-7 anti-inflammatory, antifibrotic, vasodilating, and natriuretic properties was attempted at least in some COVID-19 patients through i.v. infusion of recombinant human ACE2 or intranasal administration of the modified ACE2 protein, with inconsistent clinical results. Conversely, use of ACE inhibitors (ACEis), which increase ACE2 cell expression, seemed to improve the prognosis of hypertensive patients with COVID-19. To restore Ang1-7 tissue levels in all these viral diseases and avoid the untoward effects frequently seen with ACE2 systemic administration, a different strategy may be hypothesized. Experimentally, when metallopeptidase inhibitors block ACE2, neprilysin (NEP), highly expressed in higher and lower airways, starts cleaving angiotensin I (Ang I) into Ang1-7. We suggest a discerning use of ACEis in normohypertensive patients with -coronavirus disease as well as in atypical pneumonia caused by avian influenza viruses or hRSV to block the main ACE-dependent effects: Ang II synthesis and Ang1-7 degradation into angiotensin 1-5. At the same time, i.v.-infused Ang I, which is not hypertensive provided ACE is inhibited, may become the primary substrate for local Ang1-7 synthesis via ubiquitous NEP; i.e., NEP could replace inadequate ACE2 function if Ang I was freely available. Moreover, inhibitors of chymase, a serine endopeptidase responsible for 80% of Ang II-forming activity in tissues and vessel walls, could protect patients with atypical pneumonia from Ang II-mediated microvascular damage without reducing arterial blood pressure.
Topics: Animals; Humans; Renin-Angiotensin System; COVID-19; SARS-CoV-2; Peptidyl-Dipeptidase A; Angiotensin-Converting Enzyme 2; Influenza A Virus, H5N1 Subtype; Influenza A Virus, H7N9 Subtype; Angiotensin-Converting Enzyme Inhibitors; Angiotensin II; Hypertension
PubMed: 37476705
DOI: 10.1155/2023/3362391 -
Fitoterapia Apr 2024Angiotensin I-converting enzyme (ACE) inhibition is currently a common method for the treatment and control of hypertension. In this study, four new (1-4) and one known...
Angiotensin I-converting enzyme (ACE) inhibition is currently a common method for the treatment and control of hypertension. In this study, four new (1-4) and one known (5) cycloartane triterpenoids were isolated from the leaves of Swietenia macrophylla by chromatographic techniques and identified by their spectroscopic data and a comprehensive comparison of published data. The triterpenoids were evaluated for their ACE inhibitory potential using in vitro inhibition assays and in silico methods. The inhibition assay and enzyme kinetics results showed that the most active triterpenoid, compound 4, inhibited ACE in a mixed-type manner with an IC value of 57.7 ± 6.07 μM. Computer simulations revealed that compound 4 reduces the catalytic efficiency of ACE by competitive insertion into the active pocket blocking the substrate, and the binding activity occurs mainly through hydrogen bonds and hydrophobic interactions. The study showed that S. macrophylla can be a source of bioactive material and the ACE inhibitory triterpenoid could be a potential antihypertensive agent.
Topics: Angiotensin-Converting Enzyme Inhibitors; Molecular Docking Simulation; Molecular Structure; Triterpenes; Meliaceae; Angiotensins
PubMed: 38354823
DOI: 10.1016/j.fitote.2024.105862 -
Molecular Biology Reports Aug 2023Angiotensin Converting Enzyme or ACE is an exo-peptidase that causes the conversion of angiotensin I to angiotensin II, vasoconstriction, and aldosterone production. ACE...
INTRODUCTION
Angiotensin Converting Enzyme or ACE is an exo-peptidase that causes the conversion of angiotensin I to angiotensin II, vasoconstriction, and aldosterone production. ACE gene polymorphism (I/D) affects enzyme activity and the risk of coronary artery disease or CAD.
AIMS
To examine the role of ACE (I/D) Gene Polymorphisms by Stent Types (Biomime, Supraflex, Xience) the Ace gene allele and genotype frequencies were determined in patients who underwent angioplasty.
MATERIAL & METHODS
Patients with in-stent restenosis (ISR) (N = 53) and patients as non-ISR group (ISR) (N = 68) have been enrolled in this study based on follow-up angiography > 1 year after PCI. Frequencies of allele and genotypes of the ACE (I/D) variant were determined using polymerase chain reaction (PCR).
RESULTS
The genotypes and allele frequencies were not significantly different between the studied populations (p-Values > 0.05). However, there was a significant difference between people with a history of Clopidogrel use in the ISR- and ISR + groups observed (p-Values > 0.005).
CONCLUSION
In the present study, there was no statistically significant relationship between ACE (I/D) gene polymorphism and the incidence of restenosis in patients who underwent repeat angiography. The results showed that the number of patients who received Clopidogrel in the ISR + group was significantly less than the ISR- group. This issue can indicate the inhibitory effect of Clopidogrel in the recurrence of stenosis.
Topics: Humans; Peptidyl-Dipeptidase A; Coronary Restenosis; Constriction, Pathologic; Clopidogrel; Percutaneous Coronary Intervention; Polymorphism, Genetic; Stents; Risk Factors
PubMed: 37328581
DOI: 10.1007/s11033-023-08554-7 -
Diabetes/metabolism Research and Reviews Nov 2023Angiotensin I-converting enzyme type 2 (ACE2), a pivotal SARS-CoV-2 receptor, has been shown to be expressed in multiple cells, including human pancreatic beta-cells. A...
AIMS
Angiotensin I-converting enzyme type 2 (ACE2), a pivotal SARS-CoV-2 receptor, has been shown to be expressed in multiple cells, including human pancreatic beta-cells. A putative bidirectional relationship between SARS-CoV-2 infection and diabetes has been suggested, confirming the hypothesis that viral infection in beta-cells may lead to new-onset diabetes or worse glycometabolic control in diabetic patients. However, whether ACE2 expression levels are altered in beta-cells of diabetic patients has not yet been investigated. Here, we aimed to elucidate the in situ expression pattern of ACE2 in Type 2 diabetes (T2D) with respect to non-diabetic donors which may account for a higher susceptibility to SARS-CoV-2 infection in beta-cells.
MATERIAL AND METHODS
Angiotensin I-converting enzyme type 2 immunofluorescence analysis using two antibodies alongside insulin staining was performed on formalin-fixed paraffin embedded pancreatic sections obtained from n = 20 T2D and n = 20 non-diabetic (ND) multiorgan donors. Intensity and colocalisation analyses were performed on a total of 1082 pancreatic islets. Macrophage detection was performed using anti-CD68 immunohistochemistry on serial sections from the same donors.
RESULTS
Using two different antibodies, ACE2 expression was confirmed in beta-cells and in pancreas microvasculature. Angiotensin I-converting enzyme type 2 expression was increased in pancreatic islets of T2D donors in comparison to ND controls alongside with a higher colocalisation rate between ACE2 and insulin using both anti-ACE2 antibodies. CD68 cells tended to be increased in T2D pancreata, in line with higher ACE2 expression observed in serial sections.
CONCLUSIONS
Higher ACE2 expression in T2D islets might increase their susceptibility to SARS-CoV-2 infection during COVID-19 in T2D patients, thus worsening glycometabolic outcomes and disease severity.
Topics: Humans; Angiotensin-Converting Enzyme 2; COVID-19; Diabetes Mellitus, Type 2; Insulin; Islets of Langerhans; Peptidyl-Dipeptidase A
PubMed: 37466955
DOI: 10.1002/dmrr.3696 -
Molecular Biology Reports Jun 2024Acute leukemias (ALs) are the most common cancers in pediatric population. There are two types of ALs: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia... (Review)
Review
Acute leukemias (ALs) are the most common cancers in pediatric population. There are two types of ALs: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Some studies suggest that the Renin Angiotensin System (RAS) has a role in ALs. RAS signaling modulates, directly and indirectly, cellular activity in different cancers, affecting tumor cells and angiogenesis. Our review aimed to summarize the role of RAS in ALs and to explore future perspectives for the treatment of these hematological malignancies by modulating RAS molecules. The database including Pubmed, Scopus, Cochrane Library, and Scielo were searched to find articles about RAS molecules in ALL and in pediatric patients. The search terms were "RAS", "Acute Leukemia", "ALL", "Angiotensin-(1-7)", "Pediatric", "Cancer", "Angiotensin II", "AML". In the bone marrow, RAS has been found to play a key role in blood cell formation, affecting several processes including apoptosis, cell proliferation, mobilization, intracellular signaling, angiogenesis, fibrosis, and inflammation. Local tissue RAS modulates tumor growth and metastasis through autocrine and paracrine actions. RAS mainly acts via two molecules, Angiotensin II (Ang II) and Angiotensin (1-7) [Ang-(1-7)]. While Ang II promotes tumor cell growth and stimulates angiogenesis, Ang-(1-7) inhibits the proliferation of neoplastic cells and the angiogenesis, suggesting a potential therapeutic role of this molecule in ALL. The interaction between ALs and RAS reveals a complex network of molecules that can affect the hematopoiesis and the development of hematological cancers. Understanding these interactions could pave the way for innovative therapeutic approaches targeting RAS components.
Topics: Humans; Renin-Angiotensin System; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Angiotensin II; Leukemia, Myeloid, Acute; Signal Transduction; Angiotensin I; Neovascularization, Pathologic; Animals; Peptide Fragments
PubMed: 38904729
DOI: 10.1007/s11033-024-09659-3 -
Journal of Agricultural and Food... Jul 2023This study aimed to identify angiotensin I-converting enzyme (ACE) from digestion products of pork sausage with partial substitution of NaCl by KCl (PSRK). Peptides...
This study aimed to identify angiotensin I-converting enzyme (ACE) from digestion products of pork sausage with partial substitution of NaCl by KCl (PSRK). Peptides from digestion products of PSRK were identified through liquid chromatography with tandem mass spectrometry analysis coupled with de novo sequencing. Subsequently, the ACE inhibitory peptides LIVGFPAYGH and IVGFPAYGH were screened based on PeptideRanker, absorption, molecular docking, and the determination of ACE inhibitory activity. In addition, the ACE inhibitory peptides LIVGFPAYGH and IVGFPAYGH were mixed-type inhibitors; these peptides' ACE inhibitory activities were expressed as the 50% inhibitory concentration (IC) values , which were 196.16 and 150.88 μM, respectively. After 2 h of incubation, LIVGFPAYGH and IVGFPAYGH could be transported through Caco-2 cell monolayers with paracellular passive diffusion. Furthermore, LIVGFPAYGH and IVGFPAYGH significantly increased the levels of ACE2 and nitric oxide while decreasing the levels of ACE, angiotensin II, and endothelin-1 in Ang I-treated human umbilical vein endothelial cells, indicating the ACE inhibitory effect of LIVGFPAYGH and IVGFPAYGH. In summary, LIVGFPAYGH and IVGFPAYGH from PSRK can be used as functional foods with antihypertensive activity.
Topics: Animals; Humans; Swine; Angiotensin-Converting Enzyme Inhibitors; Peptidyl-Dipeptidase A; Sodium Chloride; Molecular Docking Simulation; Caco-2 Cells; Endothelial Cells; Pork Meat; Red Meat; Peptides; Digestion
PubMed: 37406188
DOI: 10.1021/acs.jafc.3c01149 -
Journal of Clinical Medicine Jul 2023Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous condition predominantly affecting autonomic control of the cardiovascular system. Its extensive...
BACKGROUND
Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous condition predominantly affecting autonomic control of the cardiovascular system. Its extensive symptom diversity implies multi-organ involvement that interacts in ways still requiring full exploration. Current understanding of POTS pathophysiology suggests alterations in the renin-angiotensin-aldosterone system as a possible contributing factor. Therefore, we investigated the relationship between the activity of the renin-angiotensin-aldosterone system and hemodynamic parameters in a cohort of POTS patients and controls recruited at a tertiary referral center.
METHODS
The case-control study included 46 patients with POTS (27 ± 9 years), and 48 healthy controls (30 ± 9 years) without orthostatic intolerance. Plasma renin activity, expressed as angiotensin I generation, and plasma aldosterone were measured by enzyme-linked immunosorbent assay and were correlated with hemodynamic parameters obtained during active standing tests.
RESULTS
Renin activity was significantly downregulated in POTS patients compared to healthy individuals (median, 3406 ng/mL vs. 9949 ng/mL, < 0.001), whereas aldosterone concentration did not differ between POTS and healthy controls (median, 218 pmol/L vs. 218 pmol/L, = 0.26). A significant inverse correlation between renin activity and supine and orthostatic blood pressure levels was observed in healthy individuals ( < 0.05 for all), but not in POTS patients.
CONCLUSIONS
Renin activity, but not aldosterone concentration, is downregulated in patients with POTS. Moreover, renin activity in POTS is dissociated from supine and standing blood pressure levels in contrast to healthy individuals. These findings suggest impaired renin function in POTS, which may direct future therapeutic approaches.
PubMed: 37510775
DOI: 10.3390/jcm12144660 -
Respiratory Physiology & Neurobiology Oct 2023Evidence suggest that the renin-angiotensin system (RAS) is activated in people with asthma, although its pathophysiological role is unclear. Angiotensin-converting...
OBJECTIVE
Evidence suggest that the renin-angiotensin system (RAS) is activated in people with asthma, although its pathophysiological role is unclear. Angiotensin-converting enzyme 2 (ACE2) is the major enzyme that converts angiotensin II to angiotensin 1-7 (Ang-1-7), and is also known as a receptor of SARS-CoV-2. The current study was conducted to identify the change in RAS-related gene expression in airways of a murine asthma model.
METHODS
The ovalbumin (OA)-sensitized mice were repeatedly challenged with aerosolized OA to induce asthmatic reaction. Twenty-four hours after the last antigen challenge, the main bronchial smooth muscle (BSM) tissues were isolated.
RESULTS
The KEGG pathway analysis of differentially expressed genes in our published microarray data revealed a significant change in the RAS pathway in the antigen-challenged mice. Quantitative RT-PCR analyses showed significant increases in the angiotensin II-generating enzymes (Klk1, Klk1b3 and Klk1b8) and a significant decrease in Ace2. Surprisingly, ELISA analyses revealed a significant increase in Ang-1-7 levels in bronchoalveolar lavage (BAL) fluids of the antigen-challenged animals, while no significant change in angiotensin II was observed. Application of Ang-1-7 to the isolated BSMs had no effect on their isometrical tension.
CONCLUSION
The expression of Ace2 was downregulated in the BSMs of OA-challenged mice, while Klk1, Klk1b3 and Klk1b8 were upregulated. Despite the downregulation of ACE2, the level of its enzymatic product, Ang-1-7, was increased in the inflamed airways, suggesting the existence of an unknown ACE2-independent pathway for Ang-1-7 production. The functional role of Ang-1-7 in the airways remains unclear.
Topics: Animals; Mice; Renin-Angiotensin System; Angiotensin II; Angiotensin-Converting Enzyme 2; Down-Regulation; COVID-19; SARS-CoV-2; Asthma; Ovalbumin; Gene Expression
PubMed: 37595771
DOI: 10.1016/j.resp.2023.104137