PI3K (Phosphatidylinositol 3-Kinase) Activation and Endothelial Cell Proliferation in Patients with Hemorrhagic Hereditary Telangiectasia Type 1

Adriana Iriarte; Agnes Figueras; Pau Cerdà; José María Mora; Anna Jucglà; Rosa Penín; Francesc Viñals; Antoni Riera-Mestre

doi:10.3390/cells8090971

journal article Open Access Aug 24, 2019

PI3K (Phosphatidylinositol 3-Kinase) Activation and Endothelial Cell Proliferation in Patients with Hemorrhagic Hereditary Telangiectasia Type 1

Adriana Iriarte Agnes Figueras Pau Cerdà

José María Mora Anna Jucglà Rosa Penín Francesc Viñals Antoni Riera-Mestre

Cells Vol. 8 No. 9 pp. 971 · MDPI AG

View at Publisher Save 10.3390/cells8090971

Abstract

Hemorrhagic hereditary telangiectasia (HHT) type 2 patients have increased activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway in telangiectasia. The main objective is to evaluate the activation of the PI3K pathway in cutaneous telangiectasia of HHT1 patients. A cutaneous biopsy of a digital hand telangiectasia was performed in seven HHT1 and eight HHT2 patients and compared with six controls. The study was approved by the Clinical Research Ethics Committee of our center. A histopathological pattern with more dilated and superficial vessels that pushed up the epidermis was identified in HHT patients regardless of the type of mutation and was associated with older age, as opposed to the common telangiectasia pattern. The mean proliferation index (Ki-67) was statistically higher in endothelial cells (EC) from HHT1 than in controls. The percentage of positive EC for pNDRG1, pAKT, and pS6 in HHT1 patients versus controls resulted in higher values, statistically significant for pNDRG1 and pS6. In conclusion, we detected an increase in EC proliferation linked to overactivation of the PI3K pathway in cutaneous telangiectasia biopsies from HHT1 patients. Our results suggest that PI3K inhibitors could be used as novel therapeutic agents for HHT.

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Details

Published: Aug 24, 2019
Vol/Issue: 8(9)
Pages: 971
License: View

Authors

A

Adriana Iriarte

HHT Unit, Hospital Universitari de Bellvitge, 08907 Barcelona, Spain; Internal Medicine Department, Hospital Universitari de Bellvitge, 08907 Barcelona, Spain; Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08907 Barcelona, Spain

A

Agnes Figueras

Program Against Cancer Therapeutic Resistance, Institut Catala d’Oncologia, Hospital Duran i Reynals, L’Hospitalet de Llobregat, 08907 Barcelona, Spain; Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08907 Barcelona, Spain

P

Pau Cerdà

HHT Unit, Hospital Universitari de Bellvitge, 08907 Barcelona, Spain; Internal Medicine Department, Hospital Universitari de Bellvitge, 08907 Barcelona, Spain; Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08907 Barcelona, Spain

J

José María Mora

HHT Unit, Hospital Universitari de Bellvitge, 08907 Barcelona, Spain; Internal Medicine Department, Hospital Universitari de Bellvitge, 08907 Barcelona, Spain; Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08907 Barcelona, Spain

A

Anna Jucglà

HHT Unit, Hospital Universitari de Bellvitge, 08907 Barcelona, Spain; Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08907 Barcelona, Spain; Dermatology Department, Hospital Universitari de Bellvitge, 08907 Barcelona, Spain

R

Rosa Penín

Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08907 Barcelona, Spain; Pathological Anatomy Department, Hospital Universitari de Bellvitge, 08907 Barcelona, Spain

F

Francesc Viñals

Program Against Cancer Therapeutic Resistance, Institut Catala d’Oncologia, Hospital Duran i Reynals, L’Hospitalet de Llobregat, 08907 Barcelona, Spain; Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08907 Barcelona, Spain; Physiological Sciences Department, Faculty of Medicine and Health Sciences, Universitat de Barcelona, L’Hospitalet de Llobregat, 08907 Barcelona, Spain

A

Antoni Riera-Mestre

HHT Unit, Hospital Universitari de Bellvitge, 08907 Barcelona, Spain; Internal Medicine Department, Hospital Universitari de Bellvitge, 08907 Barcelona, Spain; Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08907 Barcelona, Spain; Clinical Sciences Department, Faculty of Medicine and Health Sciences, Universitat de Barcelona, L’Hospitalet de Llobregat, 08907 Barcelona, Spain

Funding

Instituto de Salud Carlos III Award: PI17/00669

Agencia Estatal de Investigación Award: SAF2017-85869-R

Cite This Article

Adriana Iriarte, Agnes Figueras, Pau Cerdà, et al. (2019). PI3K (Phosphatidylinositol 3-Kinase) Activation and Endothelial Cell Proliferation in Patients with Hemorrhagic Hereditary Telangiectasia Type 1. Cells, 8(9), 971. https://doi.org/10.3390/cells8090971

PI3K (Phosphatidylinositol 3-Kinase) Activation and Endothelial Cell Proliferation in Patients with Hemorrhagic Hereditary Telangiectasia Type 1

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