Abstract
Human urotensin II (U-II), the most potent vasoconstrictor undecapeptide identified to date, and its receptor (UT) are involved in the pathogenesis of systemic and pulmonary hypertension. Here, we review recent advances in our understanding of the pathophysiology of U-II with particular reference to its role in atherosclerotic cardiovascular diseases. Single-nucleotide polymorphisms of U-II gene (S89N) are associated with onset of essential hypertension, type II diabetes mellitus, and insulin resistance in the Asian population. Plasma U-II levels are elevated in patients with vascular endothelial dysfunction-related diseases such as essential hypertension, diabetes mellitus, atherosclerosis, ischemic heart disease, and heart failure. Chronic infusion of U-II enhances atherosclerotic lesions in the aorta in apolipoprotein Eknockout mice. In human atherosclerotic plaques from the aorta and coronary and carotid arteries, U-II is expressed at high levels in endothelial cells (ECs) and lymphocytes, whereas UT is expressed at high levels in vascular smooth muscle cells (VSMCs), ECs, monocytes, and macrophages. U-II stimulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in human ECs as chemoattractant for monocytes, and accelerates foam cell formation by up-regulation of acyl-coenzyme A:cholesterol acyltransferase-1 in human monocyte-derived macrophages. U-II produces reactive oxygen species (ROS) via nicotinamide adenine dinucleotide phosphate oxidase activation in human VSMCs, and stimulates VSMC proliferation with synergistic effects when combined with ROS, oxidized LDL, and serotonin. Clinical studies demonstrated increased plasma U-II levels in accordance with the severity of carotid atherosclerosis in patients with essential hypertension and that of coronary artery lesions in patients with ischemic heart disease. Here, we summarize the key roles of U-II in progression of hypertension and atherosclerotic cardiovascular diseases.
Keywords: Urotensin II, hypertension, atherosclerosis, coronary artery disease, cardiovascular medicine
Current Medicinal Chemistry
Title: Human Urotensin II Promotes Hypertension and Atherosclerotic Cardiovascular Diseases
Volume: 16 Issue: 5
Author(s): Takuya Watanabe, Shigeko Arita, Yuji Shiraishi, Toshiaki Suguro, Tetsuo Sakai, Shigeki Hongo and Akira Miyazaki
Affiliation:
Keywords: Urotensin II, hypertension, atherosclerosis, coronary artery disease, cardiovascular medicine
Abstract: Human urotensin II (U-II), the most potent vasoconstrictor undecapeptide identified to date, and its receptor (UT) are involved in the pathogenesis of systemic and pulmonary hypertension. Here, we review recent advances in our understanding of the pathophysiology of U-II with particular reference to its role in atherosclerotic cardiovascular diseases. Single-nucleotide polymorphisms of U-II gene (S89N) are associated with onset of essential hypertension, type II diabetes mellitus, and insulin resistance in the Asian population. Plasma U-II levels are elevated in patients with vascular endothelial dysfunction-related diseases such as essential hypertension, diabetes mellitus, atherosclerosis, ischemic heart disease, and heart failure. Chronic infusion of U-II enhances atherosclerotic lesions in the aorta in apolipoprotein Eknockout mice. In human atherosclerotic plaques from the aorta and coronary and carotid arteries, U-II is expressed at high levels in endothelial cells (ECs) and lymphocytes, whereas UT is expressed at high levels in vascular smooth muscle cells (VSMCs), ECs, monocytes, and macrophages. U-II stimulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in human ECs as chemoattractant for monocytes, and accelerates foam cell formation by up-regulation of acyl-coenzyme A:cholesterol acyltransferase-1 in human monocyte-derived macrophages. U-II produces reactive oxygen species (ROS) via nicotinamide adenine dinucleotide phosphate oxidase activation in human VSMCs, and stimulates VSMC proliferation with synergistic effects when combined with ROS, oxidized LDL, and serotonin. Clinical studies demonstrated increased plasma U-II levels in accordance with the severity of carotid atherosclerosis in patients with essential hypertension and that of coronary artery lesions in patients with ischemic heart disease. Here, we summarize the key roles of U-II in progression of hypertension and atherosclerotic cardiovascular diseases.
Export Options
About this article
Cite this article as:
Watanabe Takuya, Arita Shigeko, Shiraishi Yuji, Suguro Toshiaki, Sakai Tetsuo, Hongo Shigeki and Miyazaki Akira, Human Urotensin II Promotes Hypertension and Atherosclerotic Cardiovascular Diseases, Current Medicinal Chemistry 2009; 16 (5) . https://dx.doi.org/10.2174/092986709787458515
DOI https://dx.doi.org/10.2174/092986709787458515 |
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
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...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
- 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 (Hot Topic: Cardiovascular Disease Biomarkers: from Tradition to Modernity)
Current Topics in Medicinal Chemistry Hydroximic Acid Derivatives: Pleiotropic Hsp Co-Inducers Restoring Homeostasis and Robustness
Current Pharmaceutical Design Cardiac Protection via Metabolic Modulation: An Emerging Role for Incretin-Based Therapies?
Cardiovascular & Hematological Agents in Medicinal Chemistry Supplements, Diets and Other Complementary and Alternative Interventions in Adolescent Mental Health
Adolescent Psychiatry Targeting Mitochondrial Oxidative Stress Through Lipoic Acid Synthase: A Novel Strategy to Manage Diabetic Cardiovascular Disease
Cardiovascular & Hematological Agents in Medicinal Chemistry Clinical Proteomics in Application to Predictive Diagnostics and Personalized Treatment of Diabetic Patients
Current Proteomics Functional and Structural Benefits Induced by Omega-3 Polyunsaturated Fatty Acids During Aging
Current Neuropharmacology Mental Health Problems Experienced by Patients with Rheumatic Diseases During COVID-19 Pandemic
Current Rheumatology Reviews Role of Open Source Tools and Resources in Virtual Screening for Drug Discovery
Combinatorial Chemistry & High Throughput Screening An Insight into the Recent Diabetes Trials: What is the Best Approach to Prevent Macrovascular and Microvascular Complications?
Current Diabetes Reviews Curcumin Nanomicelle Improves Lipid Profile, Stress Oxidative Factors and Inflammatory Markers in Patients Undergoing Coronary Elective Angioplasty; A Randomized Clinical Trial
Endocrine, Metabolic & Immune Disorders - Drug Targets The Critical Role of Vascular Endothelial Growth Factor in Tumor Angiogenesis
Current Cancer Drug Targets Long-term Reproductive and Metabolic Consequences of PCOS
Current Diabetes Reviews Fragment Pharmacophore-Based Screening: An Efficient Approach for Discovery of New Inhibitors of Toll-Like Receptor 5
Combinatorial Chemistry & High Throughput Screening The Influence of Microneedles on the Percutaneous Penetration of Selected Antihypertensive Agents: Diltiazem Hydrochloride and Perindopril Erbumine
Current Drug Delivery HIV-Infected Patients and Liver Transplantation: Who, When and Why
Current HIV Research Nutrigenomics: Advances, Opportunities and Challenges in Understanding the Nutrient-Gene Interactions
Current Nutrition & Food Science Natalizumab Modifies Catecholamines Levels Present in Patients with Relapsing- Remitting Multiple Sclerosis
Current Pharmaceutical Design Cardiovascular-Related
Current Bioactive Compounds Nursing Assessment, Education, and Care of Extremely Premature Neonates with Patent Ductus Arteriosus
Current Pediatric Reviews