Abstract
Knowledge about the function of endothelial nitric oxide synthase (eNOS), and its regulation in pathophysiological states has tremendously increased. It is now clear that diminished activity of nitric oxide (NO) contributes to endothelial dysfunction, which is a characteristic of impeding atherosclerosis. This review aims to summarize the available knowledge about the impact of important cardiovascular risk factors on NO production by eNOS. There are 4 principle causes of diminished NO bio-activity: decreased expression and/or activity of the eNOS enzyme, eNOS uncoupling, enhanced breakdown or scavenging of NO and impaired transmission of NOmediated signaling events (failure of the effector mechanisms). From the analysis, it becomes clear, that several aspects of eNOS functionality have only scarcely been tested under conditions of increased (experimental) cardiovascular risk. These aspects include palmitoylation, myristoylation and phosphorylation of the eNOS enzyme. Clear is that enhanced production of reactive oxygen species (ROS) and eNOS uncoupling are relatively important causes of reduced NO-bioactivity in cardiovascular disease states . Ideally, eNOS is sufficiently expressed, produces NO sufficiently and not abundantly, does not produce superoxide and is not scavenged by ROS; the produced NO then reaches its signaling target, mainly soluble guanylyl cyclase (sGC) and elicits a cellular response. Considering which aspects of eNOS are now assessable in a clinical setting and which therapeutic measures are available, there is a great challenge ahead.
Keywords: Nitric oxide, eNOS uncoupling, chronic renal failure, diabetes mellitus, hypercholesterolemia, atherosclerosis
Current Pharmaceutical Design
Title: Understanding eNOS for Pharmacological Modulation of Endothelial Function: A Translational View
Volume: 13 Issue: 17
Author(s): Branko Braam and Marianne C. Verhaar
Affiliation:
Keywords: Nitric oxide, eNOS uncoupling, chronic renal failure, diabetes mellitus, hypercholesterolemia, atherosclerosis
Abstract: Knowledge about the function of endothelial nitric oxide synthase (eNOS), and its regulation in pathophysiological states has tremendously increased. It is now clear that diminished activity of nitric oxide (NO) contributes to endothelial dysfunction, which is a characteristic of impeding atherosclerosis. This review aims to summarize the available knowledge about the impact of important cardiovascular risk factors on NO production by eNOS. There are 4 principle causes of diminished NO bio-activity: decreased expression and/or activity of the eNOS enzyme, eNOS uncoupling, enhanced breakdown or scavenging of NO and impaired transmission of NOmediated signaling events (failure of the effector mechanisms). From the analysis, it becomes clear, that several aspects of eNOS functionality have only scarcely been tested under conditions of increased (experimental) cardiovascular risk. These aspects include palmitoylation, myristoylation and phosphorylation of the eNOS enzyme. Clear is that enhanced production of reactive oxygen species (ROS) and eNOS uncoupling are relatively important causes of reduced NO-bioactivity in cardiovascular disease states . Ideally, eNOS is sufficiently expressed, produces NO sufficiently and not abundantly, does not produce superoxide and is not scavenged by ROS; the produced NO then reaches its signaling target, mainly soluble guanylyl cyclase (sGC) and elicits a cellular response. Considering which aspects of eNOS are now assessable in a clinical setting and which therapeutic measures are available, there is a great challenge ahead.
Export Options
About this article
Cite this article as:
Braam Branko and Verhaar C. Marianne, Understanding eNOS for Pharmacological Modulation of Endothelial Function: A Translational View, Current Pharmaceutical Design 2007; 13 (17) . https://dx.doi.org/10.2174/138161207780831275
DOI https://dx.doi.org/10.2174/138161207780831275 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Vulnerable Atherosclerotic Plaque: Clinical Implications
Current Vascular Pharmacology Cytokine Polymorphisms in Chronic Inflammatory Diseases with Reference to Occupational Diseases
Current Molecular Medicine Pyrazolines: A Biological Review
Mini-Reviews in Medicinal Chemistry Platelets in Atherothrombosis: New and Evolving Roles
Current Pharmaceutical Design Potential Therapeutic Effects of Na+/Ca2+ Exchanger Inhibition in Cardiac Diseases
Current Medicinal Chemistry From Early Origins. When and Why does Asthma Develop?
Current Pediatric Reviews Severe Coagulation Disorder and Thrombocytopenia Associated with Tigecycline – Case Report and Review of Literature
Current Drug Safety Gender Differences in Atrial Fibrillation: A Review of Epidemiology, Management, and Outcomes
Current Cardiology Reviews Adherence to Secondary Prophylaxis for Acute Rheumatic Fever and Rheumatic Heart Disease: A Systematic Review
Current Cardiology Reviews Gender Differences in the Effects of Angiotensin Receptor Blockers on Cardiovascular Disease
Current Pharmaceutical Design Assessing The Treatment Effect in Metabolic Syndrome Without Perceptible Diabetes (ATTEMPT): A Prospective-Randomized Study in Middle Aged Men and Women
Current Vascular Pharmacology Endocrinology and Immunology of Obesity, Obesity Vaccines
Current Clinical Pharmacology A Review of the Characteristics, Properties and Methods for Quantification of Roxithromycin
Current Pharmaceutical Analysis Sympathetic and Baroreflex Function in Hypertension: Implications for Current and New Drugs
Current Pharmaceutical Design Blood-Brain Barrier Integrity and Glial Support: Mechanisms that can be Targeted for Novel Therapeutic Approaches in Stroke
Current Pharmaceutical Design Microbial Biotransformation: Recent Developments on Steroid Drugs
Recent Patents on Biotechnology A Review on Phytochemistry and Pharmacology of Medicinal as well as Poisonous Mushrooms
Mini-Reviews in Medicinal Chemistry Psoriasis and Atherosclerosis: Is There a Need For Novel Biomarkers Assessing Cardiovascular Risk?
Current Pharmaceutical Design In the Search of the Vulnerable Plaque: Current Diagnostic Techniques and Future Directions
Vascular Disease Prevention (Discontinued) Untargeted Metabolomics in the Discovery of Novel Biomarkers and Therapeutic Targets for Atherosclerotic Cardiovascular Diseases
Cardiovascular & Hematological Disorders-Drug Targets