Vascular TSP1-CD47 signaling promotes sickle cell-associated arterial vasculopathy and pulmonary hypertension in mice.


Journal

American journal of physiology. Lung cellular and molecular physiology
ISSN: 1522-1504
Titre abrégé: Am J Physiol Lung Cell Mol Physiol
Pays: United States
ID NLM: 100901229

Informations de publication

Date de publication:
01 06 2019
Historique:
pubmed: 21 3 2019
medline: 25 3 2020
entrez: 21 3 2019
Statut: ppublish

Résumé

Pulmonary hypertension (PH) is a leading cause of death in sickle cell disease (SCD) patients. Hemolysis and oxidative stress contribute to SCD-associated PH. We have reported that the protein thrombospondin-1 (TSP1) is elevated in the plasma of patients with SCD and, by interacting with its receptor CD47, limits vasodilation of distal pulmonary arteries ex vivo. We hypothesized that the TSP1-CD47 interaction may promote PH in SCD. We found that TSP1 and CD47 are upregulated in the lungs of Berkeley (BERK) sickling (Sickle) mice and patients with SCD-associated PH. We then generated chimeric animals by transplanting BERK bone marrow into C57BL/6J (

Identifiants

pubmed: 30892078
doi: 10.1152/ajplung.00302.2018
pmc: PMC6620668
doi:

Substances chimiques

CD47 Antigen 0
Cd47 protein, mouse 0
Reactive Oxygen Species 0
Thrombospondin 1 0
Thbs1 protein, mouse 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

L1150-L1164

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL079207
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142248
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL110849
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL103455
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL112914
Pays : United States

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Auteurs

Enrico M Novelli (EM)

Heart, Lung, Blood, and Vascular Medicine Institute and Division of Hematology/Oncology, UPMC Department of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.

Lynda Little-Ihrig (L)

Heart, Lung, Blood, and Vascular Medicine Institute and Division of Hematology/Oncology, UPMC Department of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.

Heather E Knupp (HE)

UPMC Children's Hospital of Pittsburgh , Pittsburgh, Pennsylvania.

Natasha M Rogers (NM)

Department of Medicine, Westmead Clinical School, University of Sydney , Sydney, New South Wales , Australia.

Mingyi Yao (M)

Department of Pharmaceutical Science, Midwestern University , Glendale, Arizona.

Jeffrey J Baust (JJ)

Heart, Lung, Blood, and Vascular Medicine Institute and Division of Hematology/Oncology, UPMC Department of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.

Daniel Meijles (D)

School of Biological Sciences, University of Reading , Reading , United Kingdom.

Claudette M St Croix (CM)

Center for Biologic Imaging, University of Pittsburgh , Pittsburgh, Pennsylvania.

Mark A Ross (MA)

Center for Biologic Imaging, University of Pittsburgh , Pittsburgh, Pennsylvania.

Patrick J Pagano (PJ)

Heart, Lung, Blood, and Vascular Medicine Institute and Division of Hematology/Oncology, UPMC Department of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.

Evan R DeVallance (ER)

Heart, Lung, Blood, and Vascular Medicine Institute and Division of Hematology/Oncology, UPMC Department of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.

George Miles (G)

Department of Molecular and Human Genetics, Baylor College of Medicine , Houston, Texas.

Karin P Potoka (KP)

Heart, Lung, Blood, and Vascular Medicine Institute and Division of Hematology/Oncology, UPMC Department of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.
UPMC Children's Hospital of Pittsburgh , Pittsburgh, Pennsylvania.

Jeffrey S Isenberg (JS)

Heart, Lung, Blood, and Vascular Medicine Institute and Division of Hematology/Oncology, UPMC Department of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.

Mark T Gladwin (MT)

Heart, Lung, Blood, and Vascular Medicine Institute and Division of Hematology/Oncology, UPMC Department of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.

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Classifications MeSH