Deregulation of Drosha in the pathogenesis of hereditary hemorrhagic telangiectasia

Purpose of review The TGFβ (transforming growth factor β) superfamily – a large group of structurally related and evolutionarily conserved proteins – profoundly shapes and organizes the vasculature during normal development and adult homeostasis. Mutations inactivating several of its ligands, receptors, or signal transducers set off hereditary hemorrhagic telangiectasia (HHT), a disorder that causes capillary networks to form incorrectly. Drosha, an essential microRNA-processing enzyme, also interfaces with TGFβ signal transducers, but its involvement in vascular conditions had not been tested until recently. This review summarizes current evidence that links mutations of Drosha to HHT. Recent findings Genetic studies have revealed that rare missense mutations in the Drosha gene occur more commonly among HHT patients than in healthy people. Molecular analyses also indicated that Drosha enzymes with HHT-associated mutations generate microRNAs less efficiently than their wild-type counterpart when stimulated by TGFβ ligands. In zebrafish or mouse, mutant Drosha proteins cause the formation of dilated, leaky blood vessels deprived of capillaries, similar to those typically found in patients with HHT. Summary Recent evidence suggests that Drosha-mediated microRNA biogenesis contributes significantly to the control of vascular development and homeostasis by TGFβ. Loss or reduction of Drosha function may predispose carriers to HHT and po...
Source: Current Opinion in Hematology - Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research

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Source: Orphanet Journal of Rare Diseases - Category: Internal Medicine Authors: Tags: Research Source Type: research
Arch Cardiol Mex. 2021 Sep 7. doi: 10.24875/ACM.21000066. Online ahead of print.ABSTRACTHereditary hemorrhagic telangiectasia (HHT) or Osler Weber Rendu Syndrome (OWRS) is a multiorgan disorder, of autosomal dominant inheritance, resulting in fibrovascular dysplasia with multiple arteriovenous malformations in different organs1. Pulmonary arteriovenous malformations are the most common pulmonary findings found in patients with HHT2,3. They can be asymptomatic or may present various symptoms such as cyanosis, dyspnea, heart failure, hemoptysis, and paradoxical embolism4.PMID:34491248 | DOI:10.24875/ACM.21000066
Source: Archivos de Cardiologia de Mexico - Category: Cardiology Authors: Source Type: research
Hereditary hemorrhagic telangiectasia is an autosomal dominant hereditary hemorrhagic disease. Its main feature is an abnormal structure of the blood vessel wall. Cirrhosis of the liver is a common chronic pro...
Source: BMC Gastroenterology - Category: Gastroenterology Authors: Tags: Case report Source Type: research
To estimate the prevalence and identify characteristics associated with the presence of aneurysms in a cohort of patients with hereditary hemorrhagic telangiectasia (HHT).
Source: Journal of Vascular and Interventional Radiology : JVIR - Category: Radiology Authors: Tags: Clinical Study Source Type: research
This article also reviews the guidelines, outcomes, risks, and challenges of genetic counseling and testing for HHT in various patient populations, and provides an algorithm for the use of genetic counseling in symptomatic and asymptomatic patients.PMID:34415050 | DOI:10.1111/cge.14050
Source: Clinical Genetics - Category: Genetics & Stem Cells Authors: Source Type: research
In this study, we evaluate the safety and efficacy of left atrial appendage occlusion (LAAO) for stroke prevention in HHT.
Source: Heart Rhythm - Category: Cardiology Authors: Source Type: research
Condition:   Telangiectasia, Hereditary Hemorrhagic Interventions:   Drug: Nintedanib;   Drug: Placebo Sponsors:   Dr. Romain Lazor;   Boehringer Ingelheim Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Ann Intern Med. 2021 Jul;174(7):1035-1036. doi: 10.7326/L21-0067.NO ABSTRACTPMID:34280351 | DOI:10.7326/L21-0067
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