Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia

  title={Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia},
  author={Franck Lebrin and Samly Srun and Karine Raymond and Sabrina Martin and Stieneke van den Brink and Catarina Freitas and Ch. Br{\'e}ant and Thomas Mathivet and Bruno Larriv{\'e}e and Jean-L{\'e}on Thomas and Helen M. Arthur and Cornelis J. J. Westermann and F. J. M. Disch and Johannes Jurgen Mager and Repke J. Snijder and Anne Eichmann and Christine L. Mummery},
  journal={Nature Medicine},
Hereditary hemorrhagic telangiectasia (HHT) is an inherited disorder characterized by vascular malformations. Many affected individuals develop recurrent nosebleeds, which can severely affect their quality of life and are clinically difficult to treat. We report here that treatment with thalidomide reduced the severity and frequency of nosebleeds (epistaxis) in the majority of a small group of subjects with HHT tested. The blood hemoglobin levels of the treated individuals rose as a result of… 

Pericytes in Hereditary Hemorrhagic Telangiectasia.

How disturbed TGF-β and VEGF signaling relates to blood vessel destabilization and HHT development is reviewed and therapeutic opportunities based on the concept of vessel normalization to treat HHT are discussed.

Anti-angiogenic therapeutic strategies in hereditary hemorrhagic telangiectasia

The experimental evidence for dysregulated angiogenesis in HHT, the anti-angiogenic therapeutic strategies used in animal models and some patients with HHT and the potential benefit of theAnti-Angiogenic treatment for ameliorating this severe, progressive vascular disease are reviewed.

Thalidomide Effects in Patients with Hereditary Hemorrhagic Telangiectasia During Therapeutic Treatment and in Fli-EGFP Transgenic Zebrafish Model

Thalidomide reverses telangiectasia and controls nosebleeds by down-regulating the expression of TGF-&bgr;3 and VEGF in HHT patients and it also leads to vascular remodeling in the zebrafish model.

Functional Alterations Involved in Increased Bleeding in Hereditary Hemorrhagic Telangiectasia Mouse Models

The results demonstrate that HHT patients with high bleeding, as determined by a high Epistaxis Severity Score (ESS), do not have prolonged clotting times or alterations in clotting factors, and support the idea that endoglin and Alk1 haploinsufficiency leads to a common phenotype of impaired hemostasis, but through different mechanisms.

Propanolol and angiogenesis inhibition in hereditary haemorrhagic telangiectasia.

  • G. Breier
  • Medicine, Biology
    Thrombosis and haemostasis
  • 2012
The development of the vascular lesions in HHT has not only been attributed to decreased TGF-β signalling but also to increased activity of the pro-angiogenic VEGF pathway, which suggests that raloxifene counteracts the haploinsufficiency of ENG and ALK1 and may be beneficial for epistaxis treatment in H HT menopausal women.

Increase of circulating endothelial cells in patients with Hereditary Hemorrhagic Telangiectasia

Hereditary Hemorrhagic Telangiectasia patients show an increase of circulating endothelial cells and a decrease of HPCs, suggesting that their active turnover characterizes the initial phase of the disease.

Thalidomide for Hereditary Hemorrhagic Telangiectasia With Pulmonary Arterial Hypertension.

Thalidomide was beneficial against mucocutaneous bleeding,1–7 but careful consideration is required with regard to its initiation in HHT patients with PAH, as reflected by serial changes in B-type natriuretic peptide and tricuspid regurgitation pressure gradient.

Thresholds of Endoglin Expression in Endothelial Cells Explains Vascular Etiology in Hereditary Hemorrhagic Telangiectasia Type 1

A positive correlation between low basal levels of endoglin and the general prevalence of clinical manifestations in selected organs is found and the development of drugs promotingendoglin expression as potentially protective is supported.

Mononuclear cells and vascular repair in HHT

A review summarizes recent studies regarding the role of MNCs in the etiology of HHT and vascular repair, and evaluates the efficacy of DPP4 inhibition in tissue integrity and repair.



Mouse Model for Hereditary Hemorrhagic Telangiectasia Has a Generalized Vascular Abnormality

A variable hemorrhagic phenotype was observed in which local bleeding is associated not only with fragile vessels but also with regions of inflammation, which has relevance to the molecular basis of vascular integrity in a wide range of diseases.

A murine model of hereditary hemorrhagic telangiectasia.

It is suggested that endoglin is critical for both angiogenesis and heart valve formation and epigenetic factors and modifier genes, some of which are present in 129/Ola, contribute to disease heterogeneity.

Bevacizumab in hereditary hemorrhagic telangiectasia.

A patient with HHT1 who had an impressive response to an anti-VEGF antibody, bevacizumab, is reported on.

Hereditary haemorrhagic telangiectasia: a clinical and scientific review

The underlying molecular, cellular and circulatory pathobiology of HHT is reviewed; clinical and genetic diagnostic strategies are explored; detailed considerations regarding screening for asymptomatic visceral involvement are presented; and overviews of management strategies are provided.

Vascular Endothelial Growth Factor Serum Levels Are Elevated in Patients with Hereditary Hemorrhagic Telangiectasia

This work is the first to suggest an increased expression of VEGF in the serum of subjects with HHT in agreement with the stimulation of V EGF synthesis proposed in the murine model.

Defective paracrine signalling by TGFβ in yolk sac vasculature of endoglin mutant mice: a paradigm for hereditary haemorrhagic telangiectasia

Analysis of TGFβ signalling in yolk sacs from endoglin knockout mice and from mice with endothelial-specific deletion of the TGF β type II receptor (TβRII) or ALK5 shows that disruption of TFT signalling in vascular endothelial cells results in reduced availability of T GFβ1 protein to promote recruitment and differentiation of smooth muscle cells, and provide a possible explanation for weak vessel walls associated with HHT.

Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation

It is demonstrated that loss of immature blood vessels is the primary cause of thalidomide-induced teratogenesis and an explanation for its action at the cell biological level is provided.

Endoglin-mediated vascular remodeling: mechanisms underlying hereditary hemorrhagic telangiectasia.

Thalidomide is an inhibitor of angiogenesis.

Electron microscopic examination of the corneal neovascularization of thalidomide-treated rabbits revealed specific ultrastructural changes similar to those seen in the deformed limb bud vasculature ofThalidomid-treated embryos, which shed light on the mechanism of the teratogenicity of the drug.

Angiogenesis and vascular malformations: antiangiogenic drugs for treatment of gastrointestinal bleeding.

Experimental and clinical data suggest that antiangiogenic substances, which were originally developed for treatment of malignant diseases, may also represent long-awaited specific drugs for the treatment of vascular malformations.