Angiotensin-converting enzyme and the tumor microenvironment: mechanisms beyond angiogenesis

2013 ◽  
Vol 305 (3) ◽  
pp. R205-R215 ◽  
Author(s):  
Derick Okwan-Duodu ◽  
Jerome Landry ◽  
Xiao Z. Shen ◽  
Roberto Diaz
Keyword(s):  
Tumor Microenvironment ◽  
Substance P ◽  
Angiotensin Converting Enzyme ◽  
Ace Inhibitors ◽  
T Regulatory Cells ◽  
Suppressor Cells ◽  
Renin Angiotensin System ◽  
Ace Inhibition ◽  
Converting Enzyme

The renin angiotensin system (RAS) is a network of enzymes and peptides that coalesce primarily on the angiotensin II type 1 receptor (AT1R) to induce cell proliferation, angiogenesis, fibrosis, and blood pressure control. Angiotensin-converting enzyme (ACE), the key peptidase of the RAS, is promiscuous in that it cleaves other substrates such as substance P and bradykinin. Accumulating evidence implicates ACE in the pathophysiology of carcinogenesis. While the role of ACE and its peptide network in modulating angiogenesis via the AT1R is well documented, its involvement in shaping other aspects of the tumor microenvironment remains largely unknown. Here, we review the role of ACE in modulating the immune compartment of the tumor microenvironment, which encompasses the immunosuppressive, cancer-promoting myeloid-derived suppressor cells, alternatively activated tumor-associated macrophages, and T regulatory cells. We also discuss the potential roles of peptides that accumulate in the setting of chronic ACE inhibitor use, such as bradykinin, substance P, and N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), and how they may undercut the gains of anti-angiogenesis from ACE inhibition. These emerging mechanisms may harmonize the often-conflicting results on the role of ACE inhibitors and ACE polymorphisms in various cancers and call for further investigations into the potential benefit of ACE inhibitors in some neoplasms.

Current Perspective on the Use of Angiotensin-Converting Enzyme Inhibitors in the Management of Coronary (Atherosclerotic) Artery Disease

1997 ◽  
Vol 31 (12) ◽  
pp. 1499-1506 ◽  
Author(s):  
Judy WM Cheng ◽  
Mimi N Ngo
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Ace Inhibitors ◽  
English Language ◽  
Data Extraction ◽  
Renin Angiotensin System ◽  
Therapeutic Monitoring ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Beneficial Effects

OBJECTIVE: To review the pathophysiology of atherosclerosis, the role of the renin—angiotensin system in atherogenesis, and studies supporting the potential beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in reducing cardiovascular events with long-term use. BACKGROUND: Through its action in converting angiotensin I to angiotensin II and by degrading bradykinin, local tissue ACE exerts many effects that can contribute to the development of atherosclerosis. Therefore, the use of ACE inhibitors can possibly result in antiatherogenic effects. Possible mechanisms for antiatherogenic effects of ACE inhibitors include: (1) reduction of blood pressure; (2) antiproliferative and antimigratory effects on vascular smooth muscle cells, neutrophils, and monocytes; (3) restoration of endothelial function; (4) stabilization of fatty plaque by preventing vasoconstriction; (5) antiplatelet effects; and (6) enhancement of endogenous fibrinolysis. DATA SOURCES: English-language clinical studies, abstracts, and review articles pertaining to the use of ACE inhibitors and atherosclerosis. STUDY SELECTION AND DATA EXTRACTION: Relevant human studies examining the role of ACE inhibitors and atherosclerosis. DATA SYNTHESIS: Studies evaluating the possible beneficial effects of ACE inhibitors in the development of atherosclerosis are reviewed and critiqued. Design of ongoing studies with clinical and surrogate end points are discussed. CONCLUSIONS: Based on current published studies, recommendations are made regarding the use of ACE inhibitors in atherosclerosis. Therapeutic monitoring parameters for efficacy and adverse effects are also reviewed.

scholarly journals The role of renin-angiotensin system and angiotensin-converting enzyme 2 (ACE2) in the development and course of viral infection COVID-19 in patients with diabetes mellitus

2020 ◽  
Vol 23 (3) ◽  
pp. 242-249
Author(s):  
O. K. Vikulova ◽  
Zamira Zuraeva ◽  
L. V. Nikankina ◽  
M. V. Shestakova
Keyword(s):  
Diabetes Mellitus ◽  
Angiotensin Converting Enzyme ◽  
Viral Infection ◽  
Ace Inhibitors ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin

The role of renin-angiotensin system (RAS) in general and angiotensin-converting enzyme 2 (ACE2) in particular in the pathogenesis and course of viral infection caused by SARS-CoV-2 (COVID-19) is of particular interest. This is due not only to the fact that ACE2 is a receptor for the virus the target cells. RAS hyperactivation in patients with arterial hypertension, cardiovascular disease and diabetes mellitus, is considered one of the most important factors for a more severe infection in persons with concomitant pathology. In addition, the effects of PAS blockage with angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin II receptor blockers (ARBs) remains one of the most discussed topics in the literature on COVID-19. Thisreview presents the data on the interaction between the virus and the main components of RAS and the factors influencing their expression level, the impact of ACE inhibitors and ARBs therapy on the disease outcome, and presents theperspectives of the treatment with recombinant ACE 2.

Endocrinologic Warfare: The Role of Angiotensin-Converting Enzyme Inhibitors in Congestive Heart Failure

1990 ◽  
Vol 3 (5) ◽  
pp. 318-331
Author(s):  
Mark A. Munger ◽  
Stephanie F. Gardner ◽  
Robert C. Jarvis
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Angiotensin Converting Enzyme ◽  
Ace Inhibitors ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Vasodilator Therapy ◽  
The Future

The angiotensin-converting enzyme (ACE) inhibitors represent the gold standard of vasodilator therapy for congestive heart failure through blunting of the endocrinologic manifestations of heart failure. The future role of these agents may be in the asymptomatic and mild stages of heart failure. ACE inhibitors have been shown to decrease morbidity and mortality with the natural history of this disease being altered. The future will bring many new ACE inhibitors to market, with the challenge for physicians and pharmacists to understand the important distinctions of each specific agent. © 1990 by W.B. Saunders Company.

scholarly journals The ANG-(1–7)/ACE2/mas axis in the regulation of nephron function

2010 ◽  
Vol 298 (6) ◽  
pp. F1297-F1305 ◽  
Author(s):  
Carlos M. Ferrario ◽  
Jasmina Varagic
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Therapeutic Interventions ◽  
Experimental Hypertension ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
A Site

The study of experimental hypertension and the development of drugs with selective inhibitory effects on the enzymes and receptors constituting the components of the circulating and tissue renin-angiotensin systems have led to newer concepts of how this system participates in both physiology and pathology. Over the last decade, a renewed emphasis on understanding the role of angiotensin-(1–7) and angiotensin-converting enzyme 2 in the regulation of blood pressure and renal function has shed new light on the complexity of the mechanisms by which these components of the renin angiotensin system act in the heart and in the kidneys to exert a negative regulatory influence on angiotensin converting enzyme and angiotensin II. The vasodepressor axis composed of angiotensin-(1–7)/angiotensin-converting enzyme 2/mas receptor emerges as a site for therapeutic interventions within the renin-angiotensin system. This review summarizes the evolving knowledge of the counterregulatory arm of the renin-angiotensin system in the control of nephron function and renal disease.

scholarly journals The Potential Role of 6-gingerol and 6-shogaol as ACE Inhibitors in Silico Study

2020 ◽  
Vol 8 (2) ◽  
pp. 210
Author(s):  
Yohanes Bare ◽  
Maria Helvina ◽  
Gabriella Chandrakirana Krisnamurti ◽  
Mansur S
Keyword(s):  
Amino Acid ◽  
Angiotensin Converting Enzyme ◽  
Binding Site ◽  
Potential Role ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Data Bank ◽  
Amino Acid Residues ◽  
Converting Enzyme

Hypertension has become the third highest cause of death in Indonesia. The condition is correlated with angiotensin-converting enzyme (ACE), and possibly managed with the use of drugs. In addition, some natural compounds, including 6-shogaol and 6-gingerol from ginger, are used to decrease blood pressure. However, the mechanism and binding site of these compounds to ACE protein is currently unclear. This study, therefore, aims to investigate the potential role of these compounds as an angiotensin-converting enzyme inhibitor. The ACE protein was downloaded from Protein Data Bank (PDB) database with the ID: 3bkk, while the 6-shogaol (CID: 5281794) and 6-gingerol (CID: 44559528) ligands were obtained from the PubChem database. Meanwhile, molecular docking was established using HEX 8.0.0 software. The analysis examined the amino acid residues and the bonds formed from these interactions. According to the results, fourteen amino acid residues were formed by the interaction between 6-shogaol and ACE, while the interaction between 6-gingerol and ACE formed eight amino acids. Also, thirteen amino acid residues in the novelty binding site of ACE were discovered to be blocked by the ligands from ginger. Therefore, the compounds have potential roles as inhibitors, and this possibly helps to prevent regulation of the renin-angiotensin system. These interactions also formed hydrogen bonds, as well as electrostatic, unfavorable, and hydrophobic sites, making the binding stronger than others. 

scholarly journals Gastrointestinal and kidney manifestations in SARS-CoV and SARS-CoV-2 infections: role of angiotensin-converting enzyme 2

2020 ◽  
Vol 25 (1) ◽  
pp. 7-20
Author(s):  
Fatemeh Maghool ◽  
◽  
Mohammad Hassan Emami ◽  
Samaneh Mohammadzadeh ◽  
Aida Heidari ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Gastrointestinal Symptoms ◽  
Renin Angiotensin System ◽  
Structural Similarity ◽  
Clinical Feature ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Kidney Impairment

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 2020, which has a substantial structural similarity to severe acute respiratory syndrome coronavirus (SARS-CoV) that caused the outbreak in 2003, is currently a threat to global health. Lung involvement is the principal clinical feature in infected patients but extra-pulmonary clinical presentations are also common. The reasons for the extensive involvement of other organs are not yet clear. Angiotensin-converting enzyme 2 (ACE2), the key peptide of renin–angiotensin system (RAS), has recently identified as a major receptor for the both SARS-CoV and SARS-CoV-2 that might be a main target of coronavirus infection. ACE2 is mainly expressed in the pulmonary pneumocytes, the small intestine enterocytes as well as the proximal tubule epithelial cells of the kidneys. In addition to the respiratory tract infection symptoms, the noticeable prevalence of gastrointestinal symptoms as well as kidney impairment in hospitalized infected patients highlights other routes of infection/transmission. In present review, we discussed the role of RAS with emphasis on ACE2 in the pathogenesis of SARS-CoV and SARS-CoV-2, particularly in gastrointestinal and kidney manifestations of the diseases.

scholarly journals SARS-CoV-2-IgG Response and the Role of ACE2 G8790A and ACE I/D Polymorphic Variants as Determinants of Covid-19 Severity-A Genetic Association Study in north Indian Population

2021 ◽  
Author(s):  
Gawharul Haq Malik ◽  
Imtiyaz A Bhat ◽  
Sadaf Rasool ◽  
Insha Bashir ◽  
Arooja Bashir ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Predictive Biomarkers ◽  
Renin Angiotensin System ◽  
Preliminary Evidence ◽  
Protective Role ◽  
Serological Response ◽  
Converting Enzyme ◽  
Polymorphic Variants ◽  
Asymptomatic Subjects

Abstract Background: Angiotensin-converting enzyme-II and Angiotensin-converting enzyme are an integral part of Renin-Angiotensin system and mediate SARS-CoV-2 infection and outcome. Here we studied the role of host antibody response to SARS-CoV-2, ACE2 G8790A single nucleotide polymorphism, and ACE insertion/deletion (ACE I/D) as key determinants of Covid-19 severity and outcome. Methods: We evaluated anti-SARS-CoV-2 IgG titers by chemiluminescence. ACE2 G8790A and ACE I/D were analyzed by polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) and PCR respectively. Results: The overall positivity rate for SARS-CoV-2-IgG was 83.72%, but a significantly lower positivity was observed in asymptomatic subjects (66.67%, p < 0.05). Anti-SARS-CoV-2 IgG levels were comparatively higher in subjects who required hospitalization (13.06 ± 14.42 vs 7.37 ± 10.79, p < 0.05). ACE2 G8790A ‘AA’ genotype was significantly higher in subjects who did not require hospitalization (OR=0.40, CI 0.14-0.71, P= 0.007). In addition, the frequency of ACE I/D ‘ID’ genotype was significantly lower in symptomatic as compared to asymptomatic subjects (OR=0.235, CI 0.09-0.56, P=0.001). Conclusion: In summary, the current study shows that serological response to SARS-CoV-2 is more pronounced in symptomatic and severe covid-19 cases. Both ACE2 G8790A ‘AA’ and ACE I/D ‘ID’ genotype were observed to show protective role as far as the severity of covid-19 infection was considered. The study provides preliminary evidence of a genetic link between the analyzed polymorphic variants and covid-19 severity suggesting a subtle way of covid-19 risk stratification and utilization of respective variants as predictive biomarkers.

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