Abstract
Hereditary Haemorrhagic Telangiectasia (HHT) or Rendu-Osler-Weber syndrome is an autosomal dominant disease characterized by local angiodysplasia affecting different organism districts. From a clinical viewpoint, HHT patients suffer from epistaxis, mucocutaneous telangiectases and arteriovenous malformations in various organs. Mutations in two known genes (ENG and ALK1) account for the majority of HHT patients. Additional loci are predicted, but the underlying genes are still to be identified. Moreover, SMAD4 mutations have been reported to cause JP-HHT combined syndrome. Both endoglin and ALK-1 bind to various growth factors in the context of the Transforming Growth Factors (TGF)-β superfamily and their expression is restricted to vascular endothelial cells and very few other cell types, such as activated monocytes. Endoglin and ALK1 mutations are thought to affect endothelial cell metabolism, angiogenesis and vascular remodelling, even if the precise mechanism leading to the HHT lesions is still obscure. Endoglin is also overexpressed in smooth muscle cells of atherosclerotic plaques, suggesting a role for this protein in atherogenesis and plaque progression, as well as in other cardiovascular diseases. Recently, we demonstrated that HHT adult patients display several deficits of both innate and adaptive immune system. Here, we investigated the function of immune cells in HHT pediatric patients. Our results clearly show that HHT children have a normal functionally immune system, and suggest that HHT patients become immunocompromised host during their lifetime, likely due to a precocious immunosenescence. Moreover, the relationship between immune responsiveness in HHT and atherosclerosis are discussed.
Keywords: Atherosclerosis, endoglin, endothelial cells, hereditary haemorrhagic telangiectasia, transforming growth factor-beta
Current Pharmaceutical Design
Title: Hereditary Haemorrhagic Telangiectasia: A Rare Disease As A Model for the Study of Human Atherosclerosis
Volume: 13 Issue: 36
Author(s): G. M. Lenato, P. Suppressa, P. Giordano, G. Guanti, E. Guastamacchia, V. Triggiani, L. Amati, F. Resta, V. Covelli, E. Jirillo and C. Sabba
Affiliation:
Keywords: Atherosclerosis, endoglin, endothelial cells, hereditary haemorrhagic telangiectasia, transforming growth factor-beta
Abstract: Hereditary Haemorrhagic Telangiectasia (HHT) or Rendu-Osler-Weber syndrome is an autosomal dominant disease characterized by local angiodysplasia affecting different organism districts. From a clinical viewpoint, HHT patients suffer from epistaxis, mucocutaneous telangiectases and arteriovenous malformations in various organs. Mutations in two known genes (ENG and ALK1) account for the majority of HHT patients. Additional loci are predicted, but the underlying genes are still to be identified. Moreover, SMAD4 mutations have been reported to cause JP-HHT combined syndrome. Both endoglin and ALK-1 bind to various growth factors in the context of the Transforming Growth Factors (TGF)-β superfamily and their expression is restricted to vascular endothelial cells and very few other cell types, such as activated monocytes. Endoglin and ALK1 mutations are thought to affect endothelial cell metabolism, angiogenesis and vascular remodelling, even if the precise mechanism leading to the HHT lesions is still obscure. Endoglin is also overexpressed in smooth muscle cells of atherosclerotic plaques, suggesting a role for this protein in atherogenesis and plaque progression, as well as in other cardiovascular diseases. Recently, we demonstrated that HHT adult patients display several deficits of both innate and adaptive immune system. Here, we investigated the function of immune cells in HHT pediatric patients. Our results clearly show that HHT children have a normal functionally immune system, and suggest that HHT patients become immunocompromised host during their lifetime, likely due to a precocious immunosenescence. Moreover, the relationship between immune responsiveness in HHT and atherosclerosis are discussed.
Export Options
About this article
Cite this article as:
Lenato M. G., Suppressa P., Giordano P., Guanti G., Guastamacchia E., Triggiani V., Amati L., Resta F., Covelli V., Jirillo E. and Sabba C., Hereditary Haemorrhagic Telangiectasia: A Rare Disease As A Model for the Study of Human Atherosclerosis, Current Pharmaceutical Design 2007; 13 (36) . https://dx.doi.org/10.2174/138161207783018572
DOI https://dx.doi.org/10.2174/138161207783018572 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employ in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, prediction, to monitor of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal fluid ...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
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...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
- 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
-
Anomalous Vascular Supply of Bronchial Circulation in Cystic Fibrosis Patients with Massive Hemoptysis
Current Respiratory Medicine Reviews A Recurrent Rare SOX9 Variant (M469V) is Associated with Congenital Vertebral Malformations
Current Gene Therapy Subject Index To Volume 12
Current Pharmaceutical Design Endothelins and Nitric Oxide: Vasoactive Modulators of Carotid Body Chemoreception
Current Neurovascular Research Basis for the Application of Analytical Models of the Bloch NMR Flow Equations for Functional Magnetic Resonance Imaging (fMRI): A Review
Recent Patents on Medical Imaging Hereditary Haemorrhagic Teleangiectasia: Diagnostic Imaging of Visceral Involvement
Current Pharmaceutical Design Ablation of T-Helper 1 Cell Derived Cytokines and of Monocyte-Derived Tumor Necrosis Factor-α in Hereditary Hemorrhagic Telangiectasia: Immunological Consequences and Clinical Considerations
Current Pharmaceutical Design Current Status of Renal Arterial Endovascular Interventions
Current Hypertension Reviews Antiplatelet Therapy And Percutaneous Coronary Interventions
Current Cardiology Reviews Anatomical Approach to Clinical Problems of Popliteal Fossa
Current Rheumatology Reviews Impact of Tracer Retention Levels on Visual Analysis of Cerebral [<sup>18</sup>F]- Florbetaben Pet Images
Current Radiopharmaceuticals Carbon Dioxide As a Standard of Care for Zero Contrast Interventions: When, Why and How?
Current Pharmaceutical Design Hemothorax
Current Respiratory Medicine Reviews Cocaine Dependence and Stroke: Pathogenesis and Management
Current Neurovascular Research The Need for an Interdisciplinary Network of Investigations on HHT
Current Pharmaceutical Design Contribution of Mast Cells to Cerebral Aneurysm Formation
Current Neurovascular Research Single-cell Technology in Stem Cell Research
Current Stem Cell Research & Therapy Protective Effect of Vitamin B Therapy on Bone and Cardiovascular Disease
Recent Patents on Cardiovascular Drug Discovery Cardiac Workup of Ischemic Stroke
Current Cardiology Reviews Selection and Evaluation of the Pediatric Epilepsy Surgical Candidates
Current Pediatric Reviews