Abstract
Micro- and macrovascular complications are major causes of disability and death in patients with diabetes mellitus. Functional impairment of endothelial activity precedes the development of morphological alterations during the progression of diabetes. This endothelial dysfunction results from reduced bioavailability of the vasodilator nitric oxide (NO), mainly due to accelerated NO degradation by reactive oxygen species (ROS). Although hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia independently contribute to endothelial dysfunction via several distinct mechanisms, increased oxidative stress seems to be the first alteration triggering several others. Mechanisms proposed to explain glucose- and lipid-induced vascular alterations in diabetes include accelerated formation of advanced glycation end-products (AGEs), protein kinase C activation, inflammatory signaling and oxidative stress. Insulin resistance with impaired PI 3-kinase effects decreases insulin mediated production of NO and reduces vasodilation, capillary recruitment and antioxidant properties of endothelium. Compensatory hyperinsulinemia enhances activation of intact MAP-kinase pathways and contributes to pro-atherogenic events by increasing secretion of endothelin-1 (ET-1), stimulating expression of adhesion molecules such as VCAM-1 and E-selectin, and inducing production of ROS. Conventional therapies to reduce hyperglycemia, dyslipidemia and insulin resistance may effectively improve endothelial function and delay the onset of vascular complications. Novel therapeutic approaches designed to inhibit AGEs formation, reduce PKC activation, decrease inflammatory signals and restore the ox/redox balance of endothelium may be predicted to ameliorate vascular function in diabetic state. This review summarizes the current knowledge on the most important mechanisms involved in endothelial dysfunction during diabetes. In addition, novel therapeutic strategies that may result from recently identified targets are also described.
Keywords: Endothelial dysfunction, diabetes, nitric oxide, reactive oxygen species, therapeutic strategies
Current Medicinal Chemistry
Title: Endothelial Dysfunction in Diabetes: From Mechanisms to Therapeutic Targets
Volume: 16 Issue: 1
Author(s): Maria Assunta Potenza, Sara Gagliardi, Carmela Nacci, Maria Rosaria Carratu and Monica Montagnani
Affiliation:
Keywords: Endothelial dysfunction, diabetes, nitric oxide, reactive oxygen species, therapeutic strategies
Abstract: Micro- and macrovascular complications are major causes of disability and death in patients with diabetes mellitus. Functional impairment of endothelial activity precedes the development of morphological alterations during the progression of diabetes. This endothelial dysfunction results from reduced bioavailability of the vasodilator nitric oxide (NO), mainly due to accelerated NO degradation by reactive oxygen species (ROS). Although hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia independently contribute to endothelial dysfunction via several distinct mechanisms, increased oxidative stress seems to be the first alteration triggering several others. Mechanisms proposed to explain glucose- and lipid-induced vascular alterations in diabetes include accelerated formation of advanced glycation end-products (AGEs), protein kinase C activation, inflammatory signaling and oxidative stress. Insulin resistance with impaired PI 3-kinase effects decreases insulin mediated production of NO and reduces vasodilation, capillary recruitment and antioxidant properties of endothelium. Compensatory hyperinsulinemia enhances activation of intact MAP-kinase pathways and contributes to pro-atherogenic events by increasing secretion of endothelin-1 (ET-1), stimulating expression of adhesion molecules such as VCAM-1 and E-selectin, and inducing production of ROS. Conventional therapies to reduce hyperglycemia, dyslipidemia and insulin resistance may effectively improve endothelial function and delay the onset of vascular complications. Novel therapeutic approaches designed to inhibit AGEs formation, reduce PKC activation, decrease inflammatory signals and restore the ox/redox balance of endothelium may be predicted to ameliorate vascular function in diabetic state. This review summarizes the current knowledge on the most important mechanisms involved in endothelial dysfunction during diabetes. In addition, novel therapeutic strategies that may result from recently identified targets are also described.
Export Options
About this article
Cite this article as:
Potenza Assunta Maria, Gagliardi Sara, Nacci Carmela, Carratu Rosaria Maria and Montagnani Monica, Endothelial Dysfunction in Diabetes: From Mechanisms to Therapeutic Targets, Current Medicinal Chemistry 2009; 16 (1) . https://dx.doi.org/10.2174/092986709787002853
DOI https://dx.doi.org/10.2174/092986709787002853 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Acute Coronary Syndromes in Patients with Atrial Fibrillation and Heart Failure. Could Novel Oral Anticoagulants be the Solution of the Optimal Antithrombotic Therapy Puzzle?
Cardiovascular & Hematological Agents in Medicinal Chemistry The Chemical Defensive System in the Pathobiology of Idiopathic Environment- Associated Diseases
Current Drug Metabolism Further Perspectives on Diabetes: NeuroRegulation of Blood Glucose
Neuroscience and Biomedical Engineering (Discontinued) The NPC1L1 Inhibitor Ezetimibe in the Treatment of the Dyslipidemia in Patients Affected by the Metabolic Syndrome: Evidences and Perspectives
Current Enzyme Inhibition A Molecular Bridge: Connecting Type 2 Diabetes and Alzheimer’s Disease
CNS & Neurological Disorders - Drug Targets Polyphenols in Disease: from Diet to Supplements
Current Pharmaceutical Biotechnology Low Osteopontin N-Terminal Fragment and Carotid Plaque Stability Associated with Statin or Antiplatelet Therapy
Current Vascular Pharmacology Prevention and treatment of atherosclerosis with flaxseed -derived compound secoisolariciresinol diglucoside
Current Pharmaceutical Design Patents in Oxidative Stress in Preeclampsia
Recent Patents on Biomarkers Topical Capsaicin for the Treatment of Neuropathic Pain
Current Drug Metabolism Levetiracetam might act as an efficacious drug to attenuate cognitive deficits of Alzheimer’s disease
Current Topics in Medicinal Chemistry New Developments in Therapeutic Agents for Legionnaires Disease
Anti-Infective Agents in Medicinal Chemistry Beta Cell Regeneration in Adult Mice: Controversy Over the Involvement of Stem Cells
Current Stem Cell Research & Therapy ROS Acts as a Double-Edged Sword in the Pathogenesis of Type 2 Diabetes Mellitus: Is Nrf2 a Potential Target for the Treatment?
Mini-Reviews in Medicinal Chemistry Novel Glycomimetics: Anomeric and N-Glycosyl Sulfonamides
Current Organic Chemistry Editorial [Hot Topic: Management of Diabetes Mellitus: The Five Pillars of Wisdom (Guest Editors: C.D.A. Stehouwer, N.C. Schaper and M. Huijberts)]
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Maturity-Onset Diabetes of the Young: An Overview with Focus on the Middle East
Current Molecular Medicine Recent Advances on the Roles of NO in Cancer and Chronic Inflammatory Disorders
Current Medicinal Chemistry Pharmacologic Vitreolysis in Diabetic Retinopathy
Current Pharmaceutical Biotechnology Recreational Drug Misuse and Stroke
Current Drug Abuse Reviews