transforming-growth-factor-beta and Epistaxis

Hereditary hemorrhagic telangiectasia (HHT) can be clinically diagnosed, but children often lack characteristic features. We report a family with homozygous growth differentiation factor 2 (

Topics: Asian People; Child; Child, Preschool; Consanguinity; Endoglin; Epistaxis; Exome Sequencing; Female; Growth Differentiation Factor 2; Homozygote; Humans; Hypoxia; INDEL Mutation; Loss of Function Mutation; Male; Pedigree; Signal Transduction; Telangiectasia, Hereditary Hemorrhagic; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A

Hereditary haemorrhagic telangiectasia is a rare systemic autosomal dominantly inherited disorder of the fibrovascular tissue with a wide variety of clinical manifestations. Diagnosis is based on the clinical Curaçao criteria or molecular genetic testing. Dilated vessels can develop into telangiectases or larger vascular malformations in various organs, calling for an interdisciplinary approach. Epistaxis and gastrointestinal bleeding can result from these vascular defects. Various conservative and interventional treatments have been described for these conditions. However, no optimal therapy exists. Treatment can become especially difficult due to progressive anaemia or when anticoagulant or anti-thrombotic therapy becomes necessary. Screening for pulmonary arteriovenous malformations (PAVM) should be performed in all confirmed and suspected patients. Treatment by percutaneous transcatheter embolotherapy and antibiotic prophylaxis is normally effective for PAVM. Cerebral or hepatic vascular malformations and rare manifestations need to be evaluated on a case-by-case basis to determine the best course of action for treatment.

Topics: Anemia, Iron-Deficiency; Antibiotic Prophylaxis; Anticoagulants; Arteriovenous Malformations; Disease Management; Embolization, Therapeutic; Epistaxis; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Hemostatics; Humans; Hypertension, Pulmonary; Intracranial Arteriovenous Malformations; Liver; Lung; Neovascularization, Pathologic; Signal Transduction; Telangiectasia, Hereditary Hemorrhagic; Thrombophilia; Transforming Growth Factor beta

Recurrent epistaxis is the most frequent clinical manifestation of hereditary haemorrhagic telangiectasia (HHT). Its treatment is difficult. Our objective was to assess the use of tranexamic acid (TA), an antifibrinolytic drug, for the treatment of epistaxis in HHT patients and to investigate in vitro the effects of TA over endoglin and ALK-1 expression and activity in endothelial cells. A prospective study was carried out on patients with epistaxis treated with oral TA in the HHT Unit of Sierrallana Hospital (Cantabria, Spain). Primary cultures of endothelial cells were treated with TA to measure the levels of endoglin and ALK-1 at the cell surface by flow cytometry. RNA levels were also measured by real-time PCR, and the transcriptional effects of TA on reporters for endoglin, ALK-1 and the endoglin/ALK-1 TGF-beta pathway were assessed. The results showed that the fourteen HHT patients treated orally with TA improved, and the frequency and severity of their epistaxis were decreased. No complications derived from the treatment were observed. Cultured endothelial cells incubated with TA exhibited increased levels of endoglin and ALK-1 at the protein and mRNA levels, enhanced TGF-beta signaling, and improved endothelial cell functions like tubulogenesis and migration. In summary, oral administration of TA proved beneficial for epistaxis treatment in selected patients with HHT. In addition to its already reported antifibrinolytic effects, TA stimulates the expression ofALK-1 and endoglin, as well as the activity of the ALK-1/endoglin pathway.

Topics: Activin Receptors, Type I; Activin Receptors, Type II; Administration, Oral; Adult; Aged; Aged, 80 and over; Antifibrinolytic Agents; Antigens, CD; Cell Movement; Cells, Cultured; Dose-Response Relationship, Drug; Endoglin; Endothelial Cells; Epistaxis; Female; Humans; Male; Middle Aged; Neovascularization, Physiologic; Plasminogen; Prospective Studies; Protein Serine-Threonine Kinases; Receptor, Transforming Growth Factor-beta Type I; Receptors, Cell Surface; Receptors, Transforming Growth Factor beta; Recurrence; RNA, Messenger; Signal Transduction; Spain; Telangiectasia, Hereditary Hemorrhagic; Time Factors; Tranexamic Acid; Transcription, Genetic; Transforming Growth Factor beta; Treatment Outcome

Topics: Activin Receptors, Type I; Activin Receptors, Type II; Antigens, CD; Arteriovenous Malformations; Blood Coagulation; Endoglin; Epistaxis; Head; Humans; Membrane Proteins; Mutation; Receptors, Cell Surface; Telangiectasia, Hereditary Hemorrhagic; Transforming Growth Factor beta; Vascular Cell Adhesion Molecule-1