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Mechanical Strain Induces Transcriptomic Reprogramming of Saphenous Vein Progenitors.
Maselli, Davide; Garoffolo, Gloria; Cassanmagnago, Giada Andrea; Vono, Rosa; Ruiter, Matthijs S; Thomas, Anita C; Madeddu, Paolo; Pesce, Maurizio; Spinetti, Gaia.
Afiliação
  • Maselli D; IRCCS MultiMedica, Milan, Italy.
  • Garoffolo G; Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
  • Cassanmagnago GA; Unità di Ingegneria Tissutale Cardiovascolare, Centro Cardiologico Monzino IRCCS, Milan, Italy.
  • Vono R; IRCCS Humanitas Research Hospital, Rozzano, Italy.
  • Ruiter MS; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.
  • Thomas AC; IRCCS MultiMedica, Milan, Italy.
  • Madeddu P; Unità di Ingegneria Tissutale Cardiovascolare, Centro Cardiologico Monzino IRCCS, Milan, Italy.
  • Pesce M; Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
  • Spinetti G; Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Front Cardiovasc Med ; 9: 884031, 2022.
Article em En | MEDLINE | ID: mdl-35711359
Intimal hyperplasia is the leading cause of graft failure in aortocoronary bypass grafts performed using human saphenous vein (SV). The long-term consequences of the altered pulsatile stress on the cells that populate the vein wall remains elusive, particularly the effects on saphenous vein progenitors (SVPs), cells resident in the vein adventitia with a relatively wide differentiation capacity. In the present study, we performed global transcriptomic profiling of SVPs undergoing uniaxial cyclic strain in vitro. This type of mechanical stimulation is indeed involved in the pathology of the SV. Results showed a consistent stretch-dependent gene regulation in cyclically strained SVPs vs. controls, especially at 72 h. We also observed a robust mechanically related overexpression of Adhesion Molecule with Ig Like Domain 2 (AMIGO2), a cell surface type I transmembrane protein involved in cell adhesion. The overexpression of AMIGO2 in stretched SVPs was associated with the activation of the transforming growth factor ß pathway and modulation of intercellular signaling, cell-cell, and cell-matrix interactions. Moreover, the increased number of cells expressing AMIGO2 detected in porcine SV adventitia using an in vivo arterialization model confirms the upregulation of AMIGO2 protein by the arterial-like environment. These results show that mechanical stress promotes SVPs' molecular phenotypic switching and increases their responsiveness to extracellular environment alterations, thus prompting the targeting of new molecular effectors to improve the outcome of bypass graft procedure.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2022 Tipo de documento: Article