Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder affecting 1 in 5,000 individuals worldwide. HHT is characterized by epistaxis, mucocutaneous and visceral telangiectasia and potentially life-threatening arteriovenous malformations (AVMs) in the brain, lungs and liver. More than 80% of mutations are found in ENG (HHT1) and ACVRL1 (HHT2) genes. Mutations in SMAD4 have also been identified in a subset of patients with a combined syndrome of HHT and juvenile polyposis. Mutations in bone morphogenetic protein 9 (BMP-9) have recently been associated with an HHT-like vascular syndrome. These 4 genes belong to the transforming growth factor-beta (TGF-ß) superfamily and play a critical role in the proper development and maintenance of blood vessels. Understanding the cross-talk between TGF-ß superfamily signaling components and their function in the maintenance of blood vessel integrity is fundamental in elucidating the pathologic mechanisms underlying HHT. Animal models of disease have been generated and applied to the study of disease pathogenesis and the generation of AVMS. Such models are currently used to test potential therapeutic interventions, including anti-angiogenic agents, which are also being evaluated in clinical trials. We encourage submissions of articles of all types (Original Research, Reviews, Methods, Hypothesis and Theory, Clinical Studies and Perspectives ) on genetics of HHT, mechanisms of disease, use of novel therapies in animal models and results of clinical trials.
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder affecting 1 in 5,000 individuals worldwide. HHT is characterized by epistaxis, mucocutaneous and visceral telangiectasia and potentially life-threatening arteriovenous malformations (AVMs) in the brain, lungs and liver. More than 80% of mutations are found in ENG (HHT1) and ACVRL1 (HHT2) genes. Mutations in SMAD4 have also been identified in a subset of patients with a combined syndrome of HHT and juvenile polyposis. Mutations in bone morphogenetic protein 9 (BMP-9) have recently been associated with an HHT-like vascular syndrome. These 4 genes belong to the transforming growth factor-beta (TGF-ß) superfamily and play a critical role in the proper development and maintenance of blood vessels. Understanding the cross-talk between TGF-ß superfamily signaling components and their function in the maintenance of blood vessel integrity is fundamental in elucidating the pathologic mechanisms underlying HHT. Animal models of disease have been generated and applied to the study of disease pathogenesis and the generation of AVMS. Such models are currently used to test potential therapeutic interventions, including anti-angiogenic agents, which are also being evaluated in clinical trials. We encourage submissions of articles of all types (Original Research, Reviews, Methods, Hypothesis and Theory, Clinical Studies and Perspectives ) on genetics of HHT, mechanisms of disease, use of novel therapies in animal models and results of clinical trials.
