Abstract
Sirolimus (rapamycin), a macrolide antibiotic approved for use as an immunosuppressive agent in the prevention of organ rejection, is a cell proliferation inhibitor and regulator of the immune response which acts through inhibition of TOR (target of rapamycin), a kinase essential to cell cycle progression. Recent studies suggest that the TOR pathway is critical to overall cell function, and at a basic mechanistic level, may be a regulator and potential therapeutic target involved in many of the major (and minor) disorders seen in man today. Cardiovascular diseases including restenosis following percutaneous coronary intervention as well as the more widespread condition of atherosclerosis, share this common involvement of TOR. The present report addresses the current state of intervention in cardiovascular disorders with Sirolimus and similar inhibitors of TOR, including the rationale for this approach and the successes observed to date. Success of the first drug-eluting stent to locally treat restenosis in the clinic is discussed, as are preclinical studies addressing a role in overall atherosclerosis in animal models. In addition, due to the known toxicities when given systemically, an approach for targeted delivery to local areas of vascular disease is discussed.
Keywords: Drug-eluting stents, Sirolimus, Rapamycin derivatives, Paclitaxel, Eluting Stent Systems, Coronary artery, neointimal hyperplasia, restenosis, taxol, coronary artery disease, drug-eluting stent, clinical trials, bare metal stent, angioplasty, sirolimus-eluting stents, Chemotherapy, -tubulin, lipophilicity, Palmaz-Schatz stents, intraintimal hemorrhage, Antiplatelet therapy, clopidogrel, angiographic stenosis, myocardial infarction, Academic Research Consortium, thrombosis, Stenting of Saphenous Vein Grafts, vascular brachytherapy, brachytherapy, chronic total occlusions, SYNTAX trial, XIENCE V stent, femoropopliteal disease
Current Pharmaceutical Design
Title: Sirolimus and its Analogs and its Effects on Vascular Diseases
Volume: 16 Issue: 36
Author(s): Steven J. Adelman
Affiliation:
Keywords: Drug-eluting stents, Sirolimus, Rapamycin derivatives, Paclitaxel, Eluting Stent Systems, Coronary artery, neointimal hyperplasia, restenosis, taxol, coronary artery disease, drug-eluting stent, clinical trials, bare metal stent, angioplasty, sirolimus-eluting stents, Chemotherapy, -tubulin, lipophilicity, Palmaz-Schatz stents, intraintimal hemorrhage, Antiplatelet therapy, clopidogrel, angiographic stenosis, myocardial infarction, Academic Research Consortium, thrombosis, Stenting of Saphenous Vein Grafts, vascular brachytherapy, brachytherapy, chronic total occlusions, SYNTAX trial, XIENCE V stent, femoropopliteal disease
Abstract: Sirolimus (rapamycin), a macrolide antibiotic approved for use as an immunosuppressive agent in the prevention of organ rejection, is a cell proliferation inhibitor and regulator of the immune response which acts through inhibition of TOR (target of rapamycin), a kinase essential to cell cycle progression. Recent studies suggest that the TOR pathway is critical to overall cell function, and at a basic mechanistic level, may be a regulator and potential therapeutic target involved in many of the major (and minor) disorders seen in man today. Cardiovascular diseases including restenosis following percutaneous coronary intervention as well as the more widespread condition of atherosclerosis, share this common involvement of TOR. The present report addresses the current state of intervention in cardiovascular disorders with Sirolimus and similar inhibitors of TOR, including the rationale for this approach and the successes observed to date. Success of the first drug-eluting stent to locally treat restenosis in the clinic is discussed, as are preclinical studies addressing a role in overall atherosclerosis in animal models. In addition, due to the known toxicities when given systemically, an approach for targeted delivery to local areas of vascular disease is discussed.
Export Options
About this article
Cite this article as:
J. Adelman Steven, Sirolimus and its Analogs and its Effects on Vascular Diseases, Current Pharmaceutical Design 2010; 16 (36) . https://dx.doi.org/10.2174/138161210794454923
DOI https://dx.doi.org/10.2174/138161210794454923 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
How to Prevent Postpartum Relapse to Smoking
Current Pediatric Reviews Traditional Cardiovascular Risk Factors in Adolescents with Type 1 Diabetes Mellitus
Current Diabetes Reviews Combining Diffusion-Weighted Imaging Patterns with ABCD2 Score Predicts Stroke Risk after Transient Ischemic Attack
Current Neurovascular Research MRI of Central Nervous System (CNS) Vasculitis
Current Medical Imaging Subject Index To Volume 12
Current Pharmaceutical Design Pharmacological Effect of Berberine Chloride in Propyl Thiouracil Induced Thyroidal Dysfunction - A Time Bound Study in Female Rats
Recent Patents on Drug Delivery & Formulation Surface Modification of Poly(Vinylchloride) for Manufacturing Advanced Catheters
Current Medicinal Chemistry Pupil Response Biomarkers Distinguish Amyloid Precursor Protein Mutation Carriers from Non-Carriers
Current Alzheimer Research Mitochondria-Associated Membranes (MAMs): A Novel Therapeutic Target for Treating Metabolic Syndrome
Current Medicinal Chemistry Polymorphism in Endothelin-1 Gene: An Overview
Current Clinical Pharmacology Inflammation, High Density Lipoprotein and Endothelium
Current Medicinal Chemistry Obesity, Diabetes and Atrial Fibrillation; Epidemiology, Mechanisms and Interventions
Current Cardiology Reviews The Prevalence of the Classical and Non-Classical Cardiovascular Risk Factors in Multiple Sclerosis Patients
CNS & Neurological Disorders - Drug Targets Radiopharmaceuticals in Neurological and Psychiatric Disorders
Current Clinical Pharmacology Subject Index to Volume 3
Current Drug Targets - Cardiovascular & Hematological Disorders Why Do Mothers Die? The Silent Tragedy of Maternal Mortality
Current Women`s Health Reviews Tauopathies – Focus on Changes at the Neurovascular Unit
Current Alzheimer Research Metabolism of Flavonoids in Human: A Comprehensive Review
Current Drug Metabolism Amyloid A Amyloidosis Secondary to Rheumatoid Arthritis: An Uncommon Yet Important Complication
Current Rheumatology Reviews Epidemiology of Type 1 Diabetes in Latin America
Current Diabetes Reviews