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...
Coronavirus Disease 2019 (COVID-19) continues to have a devastating impact across the world. A number of pre-existing common clinical conditions were reported to represent risk factors for more severe COVID-19...
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
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...
To estimate the prevalence and identify characteristics associated with the presence of aneurysms in a cohort of patients with hereditary hemorrhagic telangiectasia (HHT).
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
In this study, we evaluate the safety and efficacy of left atrial appendage occlusion (LAAO) for stroke prevention in HHT.
Condition: Telangiectasia, Hereditary Hemorrhagic Interventions: Drug: Nintedanib; Drug: Placebo Sponsors: Dr. Romain Lazor; Boehringer Ingelheim Not yet recruiting
Ann Intern Med. 2021 Jul;174(7):1035-1036. doi: 10.7326/L21-0067.NO ABSTRACTPMID:34280351 | DOI:10.7326/L21-0067