Abstract
Advanced glycation end product (AGE) and receptor (RAGE) axis play a central role in the pathogenesis of diabetic vascular complications. Since peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have been reported to reduce RAGE gene expression and subsequently suppress the downstream signalings in human umbilical vein endothelial cells (HUVECs), we examined here whether telmisartan, a unique angiotensin II type 1 receptor blocker with PPAR-γ agonistic activity, could inhibit the AGE-induced up-regulation of plasminogen activator inhibitor-1 (PAI-1) mRNA levels in HUVECs by suppressing RAGE gene expression. Telmisartan completely blocked the AGE-induced RAGE gene up-regulation in HUVECs, which was partly prevented by GW9662, an inhibitor of PPAR-γ. Further, telmisartan was also found to inhibit up-regulation of mRNA levels for PAI-1 in AGE-exposed HUVECs, which was completely prevented by GW9662. These results suggest that telmisartan inhibits the AGE-induced PAI-1 gene induction in HUVECs by down-regulating RAGE expression via PPAR-γ activation. Our present study suggests that telmisartan works as an anti-thrombogenic agent against AGEs, which may play a protective role against vascular complications in diabetes.
Keywords: AGEs, RAGE, Telmisartan, PAI-1, PPAR-γ
Letters in Drug Design & Discovery
Title: Telmisartan Blocks Advanced Glycation End Product (AGE)-Induced Plasminogen Activator Inhibitor-1 (PAI-1) Gene Expression in Endothelial Cells via Activation of Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ )
Volume: 5 Issue: 8
Author(s): Takanori Matsui, Kazuo Nakamura, Masayoshi Takeuchi and Sho-ichi Yamagishi
Affiliation:
Keywords: AGEs, RAGE, Telmisartan, PAI-1, PPAR-γ
Abstract: Advanced glycation end product (AGE) and receptor (RAGE) axis play a central role in the pathogenesis of diabetic vascular complications. Since peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have been reported to reduce RAGE gene expression and subsequently suppress the downstream signalings in human umbilical vein endothelial cells (HUVECs), we examined here whether telmisartan, a unique angiotensin II type 1 receptor blocker with PPAR-γ agonistic activity, could inhibit the AGE-induced up-regulation of plasminogen activator inhibitor-1 (PAI-1) mRNA levels in HUVECs by suppressing RAGE gene expression. Telmisartan completely blocked the AGE-induced RAGE gene up-regulation in HUVECs, which was partly prevented by GW9662, an inhibitor of PPAR-γ. Further, telmisartan was also found to inhibit up-regulation of mRNA levels for PAI-1 in AGE-exposed HUVECs, which was completely prevented by GW9662. These results suggest that telmisartan inhibits the AGE-induced PAI-1 gene induction in HUVECs by down-regulating RAGE expression via PPAR-γ activation. Our present study suggests that telmisartan works as an anti-thrombogenic agent against AGEs, which may play a protective role against vascular complications in diabetes.
Export Options
About this article
Cite this article as:
Matsui Takanori, Nakamura Kazuo, Takeuchi Masayoshi and Yamagishi Sho-ichi, Telmisartan Blocks Advanced Glycation End Product (AGE)-Induced Plasminogen Activator Inhibitor-1 (PAI-1) Gene Expression in Endothelial Cells via Activation of Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ ), Letters in Drug Design & Discovery 2008; 5 (8) . https://dx.doi.org/10.2174/157018008786898590
DOI https://dx.doi.org/10.2174/157018008786898590 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
- 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
Related Articles
-
Advances in Antithrombotic Agents
Cardiovascular & Hematological Agents in Medicinal Chemistry Editorial
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery COVID-19: Are Experimental Drugs a Cure or Cause?
Current Drug Safety Probiotics and Oral Health
Current Pharmaceutical Design Impact of Fenofibrate on Type 2 Diabetes Patients with Features of the Metabolic Syndrome: Subgroup Analysis From FIELD
Current Cardiology Reviews Exacerbations of Asthma and Chronic Obstructive Pulmonary Disease (COPD): Focus on Virus Induced Exacerbations
Current Pharmaceutical Design Ascorbic Acid: Its Role in Immune System and Chronic Inflammation Diseases
Mini-Reviews in Medicinal Chemistry Aerobic Exercise Does Not Predict Brain Derived Neurotrophic Factor And Cortisol Alterations in Depressed Patients
CNS & Neurological Disorders - Drug Targets The Epidemiology of Adiposity and Dementia
Current Alzheimer Research Novel Risk Factors Related to Stable Angina
Current Pharmaceutical Design Psychosocial Factors and Diabetes Mellitus: Evidence-Based Treatment Guidelines
Current Diabetes Reviews Headspace Analyses in Valuable and Functional Foods: Application of SPME in the Quality Control and Characterization of Olive Oils
Current Analytical Chemistry Morbidity and Mortality Associated with Pharmacotherapy. Evolution and Current Concept of Drug-Related Problems
Current Pharmaceutical Design Achieving Better Blood Pressure Control in High-Risk Patients with Type 2 Diabetes Using Combination Antihypertensive Therapy
Vascular Disease Prevention (Discontinued) Editorial: Can Glucagon Like Peptide 1 (GLP1) Agonists or Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitors Ameliorate Non-Alcoholic Steatohepatitis in People with or without Diabetes?
Current Vascular Pharmacology The Discovery and Development of Drug Combinations for the Treatment of Various Diseases from Patent Literature (1980-Present)
Current Topics in Medicinal Chemistry Statins Attenuate Fibrotic Manifestations of Cardiac Tissue Damage
Current Molecular Pharmacology Recents Patents for Isolating, Delivering and Tracking Adult Stem Cells in Regenerative Medicine
Recent Patents on Drug Delivery & Formulation Managing the Liabilities Arising from Structural Alerts: A Safe Philosophy for Medicinal Chemists
Current Medicinal Chemistry Prediction of Cardiovascular Risk Using Extreme Learning Machine-Tree Classifier on Apache Spark Cluster
Recent Advances in Computer Science and Communications