Abstract
Thrombotic complications of vascular disease constitute the leading cause of morbidity and mortality in much of the developed world. Current drug therapies available to treat the thrombotic component of arterial and venous vascular complications remain limited. Novel safe and effective treatment strategies to reduce formation of occlusive thrombosis will likely have a major impact on reducing the economic burden of vascular disease on the healthcare system. Enhancing endogenous fibrinolysis by targeting plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor of circulating plasminogen activators, has been shown to be effective in markedly attenuating the formation of arterial and venous occlusive thrombosis in animal models. In addition, animal and human studies of PAI-1 deficiency indicate that spontaneous bleeding complications associated with even complete PAI-1 deficiency would be rare. Patients most likely to benefit from PAI-1 inhibition would be those at high risk for vascular events where PAI-1 is elevated, such as is observed in obesity, diabetes and the metabolic syndrome. Since obesity and metabolic syndrome are now epidemic, and will likely have a major adverse impact on vascular thrombotic events, it may be time to test the clinical effectiveness of PAI-1 inhibition in a patient population at high risk for vascular thrombosis.
Keywords: urokinase-type plasminogen activator, atherothrombosis, protease activity, thrombolysis, vitronectin deficient mice
Current Drug Targets
Title: Plasminogen Activator Inhibitor-1 in Vascular Thrombosis
Volume: 8 Issue: 9
Author(s): Randal J. Westrick and Daniel T. Eitzman
Affiliation:
Keywords: urokinase-type plasminogen activator, atherothrombosis, protease activity, thrombolysis, vitronectin deficient mice
Abstract: Thrombotic complications of vascular disease constitute the leading cause of morbidity and mortality in much of the developed world. Current drug therapies available to treat the thrombotic component of arterial and venous vascular complications remain limited. Novel safe and effective treatment strategies to reduce formation of occlusive thrombosis will likely have a major impact on reducing the economic burden of vascular disease on the healthcare system. Enhancing endogenous fibrinolysis by targeting plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor of circulating plasminogen activators, has been shown to be effective in markedly attenuating the formation of arterial and venous occlusive thrombosis in animal models. In addition, animal and human studies of PAI-1 deficiency indicate that spontaneous bleeding complications associated with even complete PAI-1 deficiency would be rare. Patients most likely to benefit from PAI-1 inhibition would be those at high risk for vascular events where PAI-1 is elevated, such as is observed in obesity, diabetes and the metabolic syndrome. Since obesity and metabolic syndrome are now epidemic, and will likely have a major adverse impact on vascular thrombotic events, it may be time to test the clinical effectiveness of PAI-1 inhibition in a patient population at high risk for vascular thrombosis.
Export Options
About this article
Cite this article as:
Westrick J. Randal and Eitzman T. Daniel, Plasminogen Activator Inhibitor-1 in Vascular Thrombosis, Current Drug Targets 2007; 8 (9) . https://dx.doi.org/10.2174/138945007781662328
DOI https://dx.doi.org/10.2174/138945007781662328 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...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
-
Subject Index To Volume 6
Endocrine, Metabolic & Immune Disorders - Drug Targets 6-Chloro-7-methyl-3', 4'-dimethoxyflavone – a Potent Selective COX-2 Inhibitor
Medicinal Chemistry Biomarkers of Immunity and Inflammation for use in Nutrition Interventions: International Life Sciences Institute European Branch Work on Selection Criteria and Interpretation
Endocrine, Metabolic & Immune Disorders - Drug Targets Relevance of Dyslipidaemia and its Consequences in Periodontal Patients with Co-Existing Cardiovascular Disease and Diabetes Mellitus: Therapeutic Targets
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Anti-Inflammatory Agents in Mouth-Rinses For Periodontal Treatment
Clinical Anti-Inflammatory & Anti-Allergy Drugs (Discontinued) The Role of Transcription Factors in the Formation of an Arrhythmogenic Substrate in Congestive Human Heart Failure
Current Medicinal Chemistry Pharmacogenetics Strategies: From Candidate Genes to Whole-Genome Association Analysis. Exploratory or Confirmatory Studies?
Current Pharmacogenomics and Personalized Medicine A Journey into the World of Targeted Therapy: A Review of Gene Therapy, Stem Cell Therapy, and Cell Reprogramming in Cardiovascular Medicine
Recent Patents on Regenerative Medicine The Importance of Early Diagnosis and Treatment in Peripheral Arterial Disease: Insights from the PARTNERS and REACH Registries
Current Vascular Pharmacology Autosomal Dominant Hypercholesterolemia: Needs for Early Diagnosis and Cascade Screening in the Tunisian Population
Current Genomics Structure of Atherosclerotic Plaques in Different Vascular Territories: Clinical Relevance
Current Vascular Pharmacology Tissue Protective and Anti-Fibrotic Actions of Suramin: New Uses of an Old Drug
Current Clinical Pharmacology Endothelial Dysfunction: Methods of Assessment & Implications for Cardiovascular Diseases
Current Pharmaceutical Design Update on the Therapy of Behçets Disease
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Clopidogrel in Secondary Ischemic Stroke Prevention
Recent Patents on Cardiovascular Drug Discovery Potential Replication of Induced Pluripotent Stem Cells for Craniofacial Reconstruction
Current Stem Cell Research & Therapy Cardiovascular Diseases in Pregnancy - A Brief Overview
Current Cardiology Reviews Prevalence of HTN in Iran: Meta-analysis of Published Studies in 2004-2018
Current Hypertension Reviews Is the Use of Cholesterol-Lowering Drugs for the Prevention of Cardiovascular Complications in Type 2 Diabetics Evidence-Based? A Systematic Review
Reviews on Recent Clinical Trials Toll-Like Receptors and Human Disease: Lessons from Single Nucleotide Polymorphisms
Current Genomics