Abstract
The causes of increased rates of myocardial infarctions and strokes by application of non-steroidal antiinflammatory agents (NSAIDs) are unclear. Here we present a biochemical model that the long-term vascular effects of NSAIDs can be consequences of their antiproliferative cellular mechanism. The analysis of the model suggests that the intramitochondrial uncoupling of oxidative phosphorylation induced by NSAIDs increases, through a reduced activity of ATP-dependent ionic pumps, the intra-cellular calcium x phosphate product with a consecutively increased formation and export of various calcium phosphate compounds. The latter cause, by chemical replication mechanisms of arterial hydroxyapatite deposits, a metatstatic calcifying vascular process. This sclerogenic vascular mineralization corresponds to an early arteriosclerotic development resembling the Monckebergs media calcification. The mechanism shows direct analogies to the accelerated and metastatic calcification of coronary arteries seen in chronic kidney disease and dialysis. This appears an extra-cellular time-lapse version of the protracted cell model. The induction of this degenerative mechanism may explain the increased number of adverse cardiovascular, renovascular and cerebrovascular effects of NSAIDs as they are observed in long-term therapies.
Keywords: NSAID, metastatic calcification, arteriosclerosis, hypertension, chronic kidney disease, biochemical model
Medicinal Chemistry
Title: A Model on the Induction of Adverse Vascular Long-Term Effects of NSAIDs
Volume: 5 Issue: 1
Author(s): Rainer K. Liedtke
Affiliation:
Keywords: NSAID, metastatic calcification, arteriosclerosis, hypertension, chronic kidney disease, biochemical model
Abstract: The causes of increased rates of myocardial infarctions and strokes by application of non-steroidal antiinflammatory agents (NSAIDs) are unclear. Here we present a biochemical model that the long-term vascular effects of NSAIDs can be consequences of their antiproliferative cellular mechanism. The analysis of the model suggests that the intramitochondrial uncoupling of oxidative phosphorylation induced by NSAIDs increases, through a reduced activity of ATP-dependent ionic pumps, the intra-cellular calcium x phosphate product with a consecutively increased formation and export of various calcium phosphate compounds. The latter cause, by chemical replication mechanisms of arterial hydroxyapatite deposits, a metatstatic calcifying vascular process. This sclerogenic vascular mineralization corresponds to an early arteriosclerotic development resembling the Monckebergs media calcification. The mechanism shows direct analogies to the accelerated and metastatic calcification of coronary arteries seen in chronic kidney disease and dialysis. This appears an extra-cellular time-lapse version of the protracted cell model. The induction of this degenerative mechanism may explain the increased number of adverse cardiovascular, renovascular and cerebrovascular effects of NSAIDs as they are observed in long-term therapies.
Export Options
About this article
Cite this article as:
Liedtke K. Rainer, A Model on the Induction of Adverse Vascular Long-Term Effects of NSAIDs, Medicinal Chemistry 2009; 5 (1) . https://dx.doi.org/10.2174/157340609787049235
DOI https://dx.doi.org/10.2174/157340609787049235 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...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
Related Articles
-
Editorial [Hot Topic Management of Perioperative Systemic Inflammation During Cardiopulmonary Bypass: We Need a Multimodal Approach (Guest Editor: David Faraoni)]
Recent Patents on Cardiovascular Drug Discovery Inflammatory Signaling Networks as Targets for Pharmacological Intervention of Chronic Diseases
Current Signal Transduction Therapy Angiotensin II-Vasopressin Interactions in The Regulation of Cardiovascular Functions. Evidence for an Impaired Hormonal Sympathetic Reflex in Hypertension and Congestive Heart Failure
Endocrine, Metabolic & Immune Disorders - Drug Targets From the Design to the Clinical Application of Thromboxane Modulators
Current Pharmaceutical Design Structure, Function and Biological Relevance of Prolyl Oligopeptidase
Current Protein & Peptide Science Thiopurine Biotransformation and Pharmacological Effects: Contribution of Oxidative Stress
Current Drug Metabolism Editorial (Thematic Issue: Current Research, Knowledge and Controversies on High Density Lipoprotein)
Current Medicinal Chemistry High-risk Pregnancy and Perinatal Outcome: An Observational Study
Current Women`s Health Reviews The Cardiac Antihypertrophic Effects of Cyclic GMP-Generating Agents: An Experimental Framework for Novel Treatments of Left Ventricular Remodeling
Vascular Disease Prevention (Discontinued) Neurotoxicity of Insecticides
Current Medicinal Chemistry Susceptibility Genes in Hypertension
Current Pharmaceutical Design Optimal Sedation for the Ventilation of Critically Ill Patients
Current Respiratory Medicine Reviews Epigenetics in the Cerebrovascular System: Changing the Code without Altering the Sequence
Current Neurovascular Research Monoamine Oxidase Inhibitors: Perspective Design for the Treatment of Depression and Neurological Disorders
Current Enzyme Inhibition A Simplified Approach to Calculating Kinetic Parameters of Thermal Decomposition Processes for Cephalosporin and Penicillin Sodium Salts and to Evaluating their Stabilities
Current Pharmaceutical Analysis Altered Prolylcarboxypeptidase Expression and Function in Response to Different Risk Factors of Diabetes
Cardiovascular & Hematological Agents in Medicinal Chemistry Cardioembolic Stroke: Clinical Features, Specific Cardiac Disorders and Prognosis
Current Cardiology Reviews Many Drugs and Phytochemicals Can Be Activated to Biological Reactive Intermediates
Current Drug Metabolism Antihyperglycemic Effect of the Moroccan Collard Green (<i>Brassica oleracea</i> var. <i>viridis</i>) in Streptozotocin-Induced Diabetic Rats
Endocrine, Metabolic & Immune Disorders - Drug Targets Pro- to Anti-angiogenic Ratio in Preeclampsia
Current Women`s Health Reviews