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Ecto-5'-nucleotidase (Nt5e/CD73)-mediated adenosine signaling attenuates TGFß-2 induced elastin and cellular contraction.
Cuevas, Rolando A; Wong, Ryan; Joolharzadeh, Pouya; Moorhead, William J; Chu, Claire C; Callahan, Jack; Crane, Alex; Boufford, Camille K; Parise, Angelina M; Parwal, Aneesha; Behzadi, Parya; St Hilaire, Cynthia.
Afiliación
  • Cuevas RA; Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • Wong R; Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • Joolharzadeh P; Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • Moorhead WJ; Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • Chu CC; Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • Callahan J; Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • Crane A; Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • Boufford CK; Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • Parise AM; Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • Parwal A; Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • Behzadi P; Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • St Hilaire C; Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
Am J Physiol Cell Physiol ; 324(2): C327-C338, 2023 02 01.
Article en En | MEDLINE | ID: mdl-36503240
Arterial calcification due to deficiency of CD73 (ACDC) is a rare genetic disease caused by a loss-of-function mutation in the NT5E gene encoding the ecto-5'-nucleotidase (cluster of differentiation 73, CD73) enzyme. Patients with ACDC develop vessel arteriomegaly, tortuosity, and vascular calcification in their lower extremity arteries. Histological analysis shows that patients with ACDC vessels exhibit fragmented elastin fibers similar to that seen in aneurysmal-like pathologies. It is known that alterations in transforming growth factor ß (TGFß) pathway signaling contribute to this elastin phenotype in several connective tissue diseases, as TGFß regulates extracellular matrix (ECM) remodeling. Our study investigates whether CD73-derived adenosine modifies TGFß signaling in vascular smooth muscle cells (SMCs). We show that Nt5e-/- SMCs have elevated contractile markers and elastin gene expression compared with Nt5e+/+ SMCs. Ecto-5'-nucleotidase (Nt5e)-deficient SMCs exhibit increased TGFß-2 and activation of small mothers against decapentaplegic (SMAD) signaling, elevated elastin transcript and protein, and potentiate SMC contraction. These effects were diminished when the A2b adenosine receptor was activated. Our results identify a novel link between adenosine and TGFß signaling, where adenosine signaling via the A2b adenosine receptor attenuates TGFß signaling to regulate SMC homeostasis. We discuss how disruption in adenosine signaling is implicated in ACDC vessel tortuosity and could potentially contribute to other aneurysmal pathogenesis.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: 5'-Nucleotidasa / Adenosina Tipo de estudio: Prognostic_studies Idioma: En Revista: Am J Physiol Cell Physiol Asunto de la revista: FISIOLOGIA Año: 2023 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: 5'-Nucleotidasa / Adenosina Tipo de estudio: Prognostic_studies Idioma: En Revista: Am J Physiol Cell Physiol Asunto de la revista: FISIOLOGIA Año: 2023 Tipo del documento: Article