Abstract
Nitric oxide (NO) produced by endothelial NO synthase (eNOS) represents an anti-atherosclerotic principle. NO bioavailability is decreased in atherosclerosis due to increased NO inactivation by reactive oxygen species and reduced NO synthesis. Various types of vascular pathophysiology are associated with oxidative stress, with NADPH oxidases as the major source of reactive oxygen species. These inactivate NO. Also, oxidative stress is likely to be the main cause for oxidation of the essential NOS cofactor, tetrahydrobiopterin (BH4). A lack of BH4 leads to eNOS uncoupling (i.e., uncoupling of oxygen reduction from NO synthesis in eNOS). Based on these pathomechanisms, the therapeutic potential of a number of compounds is discussed in this review: (1) NO donors; (2) L-arginine; (3) folic acid; (4) BH4 and its precursor sepiapterin; (5) compounds that upregulate eNOS and concomitantly maintain eNOS activity (e.g. midostaurin, betulinic acid, ursolic acid, AVE9488 and AVE3085); (6) compounds that enhance the de novo synthesis of BH4 by stimulating expression or activity of GTP cyclohydrolase I; and (7) 3-hydroxy-3-methylglutarylcoenzyme A inhibitors (statins) and drugs interrupting the renin-angiotensin-aldosterone system. Statins, angiotensin II type 1 receptor blockers, angiotensin-converting enzyme (ACE) inhibitors, the aldosterone antagonist eplerenone and the renin inhibitor aliskiren enhance NO bioactivity and reduce atherosclerosis progression through multiple mechanisms.
Keywords: Nitric oxide, atherosclerosis, endothelial dysfunction, eNOS uncoupling, tetrahydrobiopterin
Current Pharmaceutical Design
Title: Prevention of Atherosclerosis by Interference with the Vascular Nitric Oxide System
Volume: 15 Issue: 27
Author(s): Huige Li and Ulrich Forstermann
Affiliation:
Keywords: Nitric oxide, atherosclerosis, endothelial dysfunction, eNOS uncoupling, tetrahydrobiopterin
Abstract: Nitric oxide (NO) produced by endothelial NO synthase (eNOS) represents an anti-atherosclerotic principle. NO bioavailability is decreased in atherosclerosis due to increased NO inactivation by reactive oxygen species and reduced NO synthesis. Various types of vascular pathophysiology are associated with oxidative stress, with NADPH oxidases as the major source of reactive oxygen species. These inactivate NO. Also, oxidative stress is likely to be the main cause for oxidation of the essential NOS cofactor, tetrahydrobiopterin (BH4). A lack of BH4 leads to eNOS uncoupling (i.e., uncoupling of oxygen reduction from NO synthesis in eNOS). Based on these pathomechanisms, the therapeutic potential of a number of compounds is discussed in this review: (1) NO donors; (2) L-arginine; (3) folic acid; (4) BH4 and its precursor sepiapterin; (5) compounds that upregulate eNOS and concomitantly maintain eNOS activity (e.g. midostaurin, betulinic acid, ursolic acid, AVE9488 and AVE3085); (6) compounds that enhance the de novo synthesis of BH4 by stimulating expression or activity of GTP cyclohydrolase I; and (7) 3-hydroxy-3-methylglutarylcoenzyme A inhibitors (statins) and drugs interrupting the renin-angiotensin-aldosterone system. Statins, angiotensin II type 1 receptor blockers, angiotensin-converting enzyme (ACE) inhibitors, the aldosterone antagonist eplerenone and the renin inhibitor aliskiren enhance NO bioactivity and reduce atherosclerosis progression through multiple mechanisms.
Export Options
About this article
Cite this article as:
Li Huige and Forstermann Ulrich, Prevention of Atherosclerosis by Interference with the Vascular Nitric Oxide System, Current Pharmaceutical Design 2009; 15 (27) . https://dx.doi.org/10.2174/138161209789058002
DOI https://dx.doi.org/10.2174/138161209789058002 |
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
-
Hydroximic Acid Derivatives: Pleiotropic Hsp Co-Inducers Restoring Homeostasis and Robustness
Current Pharmaceutical Design Myocardial Perfusion and Coronary Vasomotor Function: Emerging Role of PET Imaging
Vascular Disease Prevention (Discontinued) Sudden Infant Death Syndrome from Epidemiology to Pathophysiology
Current Pediatric Reviews MicroRNA Therapeutics: the Next Magic Bullet?
Mini-Reviews in Medicinal Chemistry microRNA-133: Expression, Function and Therapeutic Potential in Muscle Diseases and Cancer
Current Drug Targets General Aspects of Metal Toxicity
Current Medicinal Chemistry Potential Therapeutic Advantages of Doxorubicin when Activated by Formaldehyde to Function as a DNA Adduct-Forming Agent
Current Topics in Medicinal Chemistry Flavonoids and Chagas' Disease: The Story So Far!
Current Topics in Medicinal Chemistry Heart Failure Pharmacotherapy: Differences Between Adult and Paediatric Patients
Current Medicinal Chemistry Role of Antioxidants in Redox Regulation of Diabetic Cardiovascular Complications
Current Pharmaceutical Biotechnology Pharmacology of Ivabradine and the Effect on Chronic Heart Failure
Current Topics in Medicinal Chemistry Risk Profiles in Type 2 Diabetes (Metabolic Syndrome): Integration of IL-10 Polymorphisms and Laboratory Parameters to Identify Vascular Damages Related Complications
Current Pharmaceutical Design Hemodynamic Assessment and In vivo Catabolism of Adenosine 5’-triphosphate in Doxorubicin or Isoproterenol-induced Cardiovascular Toxicity
Drug Metabolism Letters Functions of Fukutin, a Gene Responsible for Fukuyama Type Congenital Muscular Dystrophy, in Neuromuscular System and Other Somatic Organs
Central Nervous System Agents in Medicinal Chemistry Neglected Tropical Protozoan Diseases: Drug Repositioning as a Rational Option
Current Topics in Medicinal Chemistry Coated with Nanomaterials Intraocular Lenses, Ophthalmic and Human Body Implantable Devices with High Catalytic Antioxidant Activities: A New Nanotechnology Strategy of Peroxidase Cellular Enzyme Mimics Increasing the Biocompatibility and Therapeutic Deployment of the Medical Prosthetic Device
Recent Patents on Drug Delivery & Formulation Heat Shock Paradox and a New Role of Heat Shock Proteins and their Receptors as Anti-Inflammation Targets
Inflammation & Allergy - Drug Targets (Discontinued) Dynamics of T Cells Repertoire During Trypanosoma cruzi Infection and its Post-Treatment Modulation
Current Medicinal Chemistry Measurement of Physical Changes in the Myocardium for Development of Novel Methods for Diagnosing Ischemia
Current Cardiology Reviews Voltammetric Stripping Methods for Direct Determination of Disopyramide
Current Pharmaceutical Analysis