Abstract
Prostacyclin (PGI2) is a major product of COX-2 catalyzed metabolism of arachidonic acid in the endothelium. Recent studies have demonstrated that PGI2 protects against atherothrombosis. The prostacyclin receptor knockout mice exhibit increased atherosclerosis, enhanced thrombosis, and enhanced proliferative response to carotid vascular injury with increased intima to media ratios [1-3]. Moreover, the recent withdrawal of rofecoxib (Vioxx™) due to increased cardiovascular events further supports the critical role of prostacyclin in inhibiting atherothrombosis in humans. Such studies have paralleled intense chemical biology studies to develop more stable prostacyclin analogues. Indeed a number of these analogues are currently being successfully used for the treatment of pulmonary hypertension. In this review we will summarize the current literature on some principles of prostacyclin analogue development, our current understanding of the receptor, and recent developments which implicate prostacyclin in atherothrombotic protection. More than 68 million Americans suffer from cardiovascular disease, which causes more deaths, disability and economic loss than any other group of diseases. Further clinical investigations of orally stable prostacyclin analogues for treatment of cardiovascular diseases other than pulmonary hypertension may now be warranted.
Keywords: Prostacyclin, prostacyclin receptor, G-protein coupled receptor, cyclo-oxygenase, COX-2, thrombosis, atherosclerosis
Current Medicinal Chemistry
Title: Prostacyclin, Atherothrombosis, and Cardiovascular Disease
Volume: 14 Issue: 20
Author(s): E. Arehart, S. Gleim, Z. Kasza, K.M. Fetalvero, K.A. Martin and J. Hwa
Affiliation:
Keywords: Prostacyclin, prostacyclin receptor, G-protein coupled receptor, cyclo-oxygenase, COX-2, thrombosis, atherosclerosis
Abstract: Prostacyclin (PGI2) is a major product of COX-2 catalyzed metabolism of arachidonic acid in the endothelium. Recent studies have demonstrated that PGI2 protects against atherothrombosis. The prostacyclin receptor knockout mice exhibit increased atherosclerosis, enhanced thrombosis, and enhanced proliferative response to carotid vascular injury with increased intima to media ratios [1-3]. Moreover, the recent withdrawal of rofecoxib (Vioxx™) due to increased cardiovascular events further supports the critical role of prostacyclin in inhibiting atherothrombosis in humans. Such studies have paralleled intense chemical biology studies to develop more stable prostacyclin analogues. Indeed a number of these analogues are currently being successfully used for the treatment of pulmonary hypertension. In this review we will summarize the current literature on some principles of prostacyclin analogue development, our current understanding of the receptor, and recent developments which implicate prostacyclin in atherothrombotic protection. More than 68 million Americans suffer from cardiovascular disease, which causes more deaths, disability and economic loss than any other group of diseases. Further clinical investigations of orally stable prostacyclin analogues for treatment of cardiovascular diseases other than pulmonary hypertension may now be warranted.
Export Options
About this article
Cite this article as:
E. Arehart , S. Gleim , Z. Kasza , K.M. Fetalvero , K.A. Martin and J. Hwa , Prostacyclin, Atherothrombosis, and Cardiovascular Disease, Current Medicinal Chemistry 2007; 14 (20) . https://dx.doi.org/10.2174/092986707781389637
DOI https://dx.doi.org/10.2174/092986707781389637 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Editorial (Thematic Issue: New Technological and Clinical Trends in Blood Pressure Theranostics: Is it Time to Consider a Spatio-Temporal Approach?)
Current Pharmaceutical Design Development of Nanocomponent Ointment Composition for the Treatment of Various Etiologies Wounds
Current Nanomedicine The Roles of Vitamin D and Its Analogs in Inflammatory Diseases
Current Topics in Medicinal Chemistry Combination of Therapeutic Hypothermia and Other Neuroprotective Strategies after An Ischemic Cerebral Insult
Current Neuropharmacology Renal Endothelial Dysfunction in Diabetic Nephropathy
Cardiovascular & Hematological Disorders-Drug Targets Preoperative Plasma Aldosterone Levels and Postoperative Atrial Fibrillation Occurrence Following Cardiac Surgery: A Review of Literature and Design of the ALDO-POAF Study (ALDOsterone for Prediction of Post-Operative Atrial Fibrillation)
Current Clinical Pharmacology Targeting microRNAs in Pathological Hypertrophy and Cardiac Failure
Mini-Reviews in Medicinal Chemistry Effects of Aging and Diet on Cardioprotection and Cardiometabolic Risk Markers
Current Pharmaceutical Design Effect of Flaxseed on Blood Lipid Level in Hyperlipidemic Patients
Reviews on Recent Clinical Trials Medicinal Agents in the Metabolic Syndrome
Cardiovascular & Hematological Agents in Medicinal Chemistry Inhibition of the Calcineurin-NFAT Signalling Cascade in the Treatment of Heart Failure
Recent Patents on Cardiovascular Drug Discovery The Heme-Heme Oxygenase System in Wound Healing; Implications for Scar Formation
Current Drug Targets Morbidity and Mortality Associated with Pharmacotherapy. Evolution and Current Concept of Drug-Related Problems
Current Pharmaceutical Design Pharmacological Treatment of Hypertension in Pregnancy
Current Pharmaceutical Design Editors Perspective (Throwing Caution to the Wnts)
Current Neurovascular Research Chemopreventive Properties and Molecular Mechanisms of the Bioactive Compounds in Hibiscus Sabdariffa Linne
Current Medicinal Chemistry An Integrated In Silico Method to Discover Novel Rock1 Inhibitors: Multi- Complex-Based Pharmacophore, Molecular Dynamics Simulation and Hybrid Protocol Virtual Screening
Combinatorial Chemistry & High Throughput Screening Cardiac and Renal Nitric Oxide in the Adaptation to Hypovolemic Shock
Current Enzyme Inhibition Fetal Arterial Changes in Response to Maternal Cigarette Smoking: Revisiting the Natural History of the Earliest Stage of Atherosclerosis
Current Cardiology Reviews Functional, Genetic and Biochemical Biomarkers of Peripheral Arterial Disease
Current Medicinal Chemistry