The role of endoglin in post-ischemic revascularization

60 p.-5 fig.-1 tab.Following arterial occlusion, blood vessels respond by forming a new network of functional capillaries (angiogenesis), by re-organizing pre-existing capillaries through the recruitment of smooth muscle cells to generate new arteries (arteriogenesis) and by growing and remodeling pre-existing collateral arterioles into physiologically relevant arteries (collateral development). All these processes result in the recovery of organ perfusion. The importance of endoglin in post-occlusion reperfusion is sustained by several observations: i) endoglin expression is increased in vessels showing active angiogenesis/remodeling; ii) genetic endoglin haploinsufficiency in humans causes deficient angiogenesis; and iii) the reduction of endoglin expression by gene disruption or the administration of endoglin-neutralizing antibodies reduces angiogenesis and revascularization. However, the precise role of endoglin in the several processes associated with revascularization has not been completely elucidated and, in some cases, the function ascribed to endoglin by different authors is controversial. The purpose of this review is to organize in a critical way the information available for the role of endoglin in several phenomena (angiogenesis, arteriogenesis, and collateral development) associated with post-ischemic revascularization.Peer reviewe

Endoglin-mediated angiogenic responses are regulated by its cytosolic domain

1 p.This work was supported by grants from Czech Science foundation GACR number 15-24015S, the Grant Agency of Charles University in Prague (1284214/C and 1158413/C), Charles University in Prague (SVV/2014/260064), European Regional Development Fund under the Innovative Economy Program of the European Union (grant coordinated by JCET-UJ, No POIG.01.01.02- 00-069/09), Ministerio de Economia y Competitividad of Spain (SAF2010-19222 and SAF2013-43421-R and SAF2010-1588), Junta de Castilla y Leon (GR100), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) and Red de Investigación Cooperativa en Enfermedades Renales (RD12/0021/0032; REDINREN). CIBERER and REDINREN are initiatives of the Instituto de Salud Carlos III (ISCIII) of Spain supported by FEDER funds. The Cardiovascular Phenotyping Unit of the University of Salamanca, including the telemetry equipment, was acquired with the support of the European Regional Development Funds (FEDER). Ministerio de Economia y Competitividad (BES-2008-005550). The publication is co-financed by the European Social Fund and the state budget of the Czech Republic (Project No.CZ.1.07/2.3.00/30.0061).Peer reviewe

Functional alterations involved in increased bleeding in hereditary hemorrhagic telangiectasia mouse models

16p.-7 fig.Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal-dominant genetic disorder involving defects in two predominant genes known as endoglin (ENG; HHT-1) and activin receptor-like kinase 1 (ACVRL1/ALK1; HHT-2). It is characterized by mucocutaneous telangiectases that, due to their fragility, frequently break causing recurrent epistaxis and gastrointestinal bleeding. Because of the severity of hemorrhages, the study of the hemostasis involved in these vascular ruptures is critical to find therapies for this disease. Our 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. Considering that coagulation is only one of the processes involved in hemostasis, the main objective of this study was to investigate the overall mechanisms of hemostasis in HHT-1 (Eng+/−) and HHT-2 (Alk1+/−) mouse models, which do not show HHT vascular phenotypes in the meaning of spontaneous bleeding. In Eng+/− mice, the results of in vivo and in vitro assays suggest deficient platelet-endothelium interactions that impair a robust and stable thrombus formation. Consequently, the thrombus could be torn off and dragged by the mechanical force exerted by the bloodstream, leading to the reappearance of hemorrhages. In Alk1+/− mice, an overactivation of the fibrinolysis system was observed. These results support the idea that endoglin and Alk1 haploinsufficiency leads to a common phenotype of impaired hemostasis, but through different mechanisms. This contribution opens new therapeutic approaches to HHT patients' epistaxis.This work was supported by the Junta de Castilla y León (BIO/SA70/14, GRS2135/A/2020, and GRS2314/A/2021), Fundación Mutua Madrileña (FMM AP172142019), the Instituto de Salud Carlos III (PI16/00460 and PI19/01630, co-funded by FEDER), and Consejo Superior de Investigaciones Científicas (CSIC; 201920E022 to CB). CO-I was supported by a contract from the Ministerio de Economía y Competitividad of Spain. CE-T was a fellow from the Fundación Miguel Casado San José.Peer reviewe

Soluble endoglin overexpression impairs tumor growth through angiogenesis reduction

1 p.Peer reviewe