Abstract
Angiogenesis plays a pivotal role in many pathological processes including chronic liver diseases. Various factors, such as renin-angiotensin-aldosterone system (RAAS), insulin resistance (IR), and reactive oxygen species (ROS) contribute reciprocally to promote angiogenesis. Blockade of RAAS by angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II (AngII) receptor blocker (ARB) markedly attenuates liver fibrosis and hepatocellular carcinoma (HCC) along with suppression of angiogenesis, IR, and ROS. Aldosterone (Ald), a downstream component of AngII, is also involved in these processes, and a selective Ald blocker (SAB) significantly suppressed the progression of chronic liver diseases. The IR status itself has shown to directly accelerate the progression of chronic liver diseases whereas inhibition of ROS by iron chelator suppressed it through augmentation and inhibition of neovascularization. The combination therapy of ACE-I/ARB/SAB with other clinically used agents, such as interferon, imatinib mesylate, vitamin K, iron chelator, and branched-chain amino acids (BCAA) exerted more potent inhibitory effects on the development of liver fibrosis and HCC than the treatment using a single agent alone. Collectively, the anti-angiogenic treatment targeting RAAS, IR, ROS with clinically available agents may become a new therapeutic strategy against the progression of chronic liver diseases.
Keywords: Aldosterone, Angiogenesis, Angiotensin-II, Hepatic stellate cell, Hepatocellular carcinoma, Insulin resistance, Iron chelator, Liver fibrosis, Nonalcoholic steatohepatitis, Reactive oxygen species, Vascular endothelial growth factor
Current Medicinal Chemistry
Title:Possible Involvement of Angiogenesis in Chronic Liver Diseases: Interaction Among Renin-Angiotensin-Aldosterone System, Insulin Resistance and Oxidative Stress
Volume: 19 Issue: 12
Author(s): K. Kaji, H. Yoshiji, Y. Ikenaka, R. Noguchi, Y. Aihara, Y. Shirai, A. Douhara and H. Fukui
Affiliation:
Keywords: Aldosterone, Angiogenesis, Angiotensin-II, Hepatic stellate cell, Hepatocellular carcinoma, Insulin resistance, Iron chelator, Liver fibrosis, Nonalcoholic steatohepatitis, Reactive oxygen species, Vascular endothelial growth factor
Abstract: Angiogenesis plays a pivotal role in many pathological processes including chronic liver diseases. Various factors, such as renin-angiotensin-aldosterone system (RAAS), insulin resistance (IR), and reactive oxygen species (ROS) contribute reciprocally to promote angiogenesis. Blockade of RAAS by angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II (AngII) receptor blocker (ARB) markedly attenuates liver fibrosis and hepatocellular carcinoma (HCC) along with suppression of angiogenesis, IR, and ROS. Aldosterone (Ald), a downstream component of AngII, is also involved in these processes, and a selective Ald blocker (SAB) significantly suppressed the progression of chronic liver diseases. The IR status itself has shown to directly accelerate the progression of chronic liver diseases whereas inhibition of ROS by iron chelator suppressed it through augmentation and inhibition of neovascularization. The combination therapy of ACE-I/ARB/SAB with other clinically used agents, such as interferon, imatinib mesylate, vitamin K, iron chelator, and branched-chain amino acids (BCAA) exerted more potent inhibitory effects on the development of liver fibrosis and HCC than the treatment using a single agent alone. Collectively, the anti-angiogenic treatment targeting RAAS, IR, ROS with clinically available agents may become a new therapeutic strategy against the progression of chronic liver diseases.
Export Options
About this article
Cite this article as:
Kaji K., Yoshiji H., Ikenaka Y., Noguchi R., Aihara Y., Shirai Y., Douhara A. and Fukui H., Possible Involvement of Angiogenesis in Chronic Liver Diseases: Interaction Among Renin-Angiotensin-Aldosterone System, Insulin Resistance and Oxidative Stress, Current Medicinal Chemistry 2012; 19 (12) . https://dx.doi.org/10.2174/092986712800099848
DOI https://dx.doi.org/10.2174/092986712800099848 |
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
-
Integrin Function and Signaling as Pharmacological Targets in Cardiovascular Diseases and in Cancer
Current Pharmaceutical Design A Palliative Care Approach to the Advanced Heart Failure Patient
Current Cardiology Reviews Synergy of microRNA and Stem Cell: A Novel Therapeutic Approach for Diabetes Mellitus and Cardiovascular Diseases
Current Diabetes Reviews NO Chimeras as Therapeutic Agents in Alzheimers Disease
Current Alzheimer Research Long-Term Exposure to Ambient Hydrocarbons Increases Dementia Risk in People Aged 50 Years and above in Taiwan
Current Alzheimer Research Should Percutaneous Coronary Intervention be the Standard Treatment Strategy for Significant Coronary Artery Disease in all Octogenarians?
Current Cardiology Reviews Therapeutic Potential of Erythropoietin in Retinal and Optic Nerve Diseases
CNS & Neurological Disorders - Drug Targets Application of Current Diagnostic Criteria for Arrhythmogenic Right Ventricular Cardiomyopathy in Every Day Clinical Practice
Current Pharmaceutical Design Soybean Seed Development: Fatty Acid and Phytohormone Metabolism and Their Interactions
Current Genomics Monocyte Cyclooxygenase-2 Activity: A New Therapeutic Target for Atherosclerosis?
Current Drug Targets - Cardiovascular & Hematological Disorders Current Trends in the Surgical Armamentarium for Minimally Invasive Heart Valve Therapies
Recent Patents on Biomedical Engineering (Discontinued) Sustained ELABELA Gene Therapy in High-salt Diet-induced Hypertensive Rats
Current Gene Therapy Hypothalamic mTOR: The Rookie Energy Sensor
Current Molecular Medicine Vasoproliferation and Antiproliferative Treatment Options in Pulmonary Arterial Hypertension
Recent Patents on Cardiovascular Drug Discovery Editorial: The Interplay between TSH and Lipids. What Should Clinicians Know?
Current Vascular Pharmacology Pivotal Role of the Interaction Between Herbal Medicines and Gut Microbiota on Disease Treatment
Current Drug Targets Paracrine Mechanisms Involved in Mesenchymal Stem Cell Differentiation into Cardiomyocytes
Current Stem Cell Research & Therapy Pharmacological and Non Pharmacological Strategies in the Management of Coronary Artery Disease and Chronic Kidney Disease
Current Cardiology Reviews Clinical Trials Using Vasodilators in Pulmonary Arterial Hypertension:Where Do We Go from Here?
Reviews on Recent Clinical Trials Use of Chronic Disease Registries to Optimize Cardiovascular Health
Current Vascular Pharmacology