Myeloid PHD2 Conditional Knockout Improves Intraplaque Angiogenesis and Vascular Remodeling in a Murine Model of Venous Bypass Grafting.

atherosclerosis hypoxia intraplaque angiogenesis intraplaque hemorrhage macrophage vein graft disease

Journal

Journal of the American Heart Association
ISSN: 2047-9980
Titre abrégé: J Am Heart Assoc
Pays: England
ID NLM: 101580524

Informations de publication

Date de publication:
23 Jan 2024
Historique:
medline: 23 1 2024
pubmed: 23 1 2024
entrez: 23 1 2024
Statut: aheadofprint

Résumé

Intraplaque angiogenesis occurs in response to atherosclerotic plaque hypoxia, which is driven mainly by highly metabolically active macrophages. Improving plaque oxygenation by increasing macrophage hypoxic signaling, thus stimulating intraplaque angiogenesis, could restore cellular function and neovessel maturation, and decrease plaque formation. Prolyl hydroxylases (PHDs) regulate cellular responses to hypoxia. We therefore aimed to elucidate the role of myeloid PHD2, the dominant PHD isoform, on intraplaque angiogenesis in a murine model for venous bypass grafting. Myeloid PHD2 conditional knockout (PHD2cko) and PHD2 wild type mice on an Ldlr Myeloid PHD2cko reduces vein graft disease and ameliorates vein graft lesion stability by improving intraplaque angiogenesis.

Sections du résumé

BACKGROUND BACKGROUND
Intraplaque angiogenesis occurs in response to atherosclerotic plaque hypoxia, which is driven mainly by highly metabolically active macrophages. Improving plaque oxygenation by increasing macrophage hypoxic signaling, thus stimulating intraplaque angiogenesis, could restore cellular function and neovessel maturation, and decrease plaque formation. Prolyl hydroxylases (PHDs) regulate cellular responses to hypoxia. We therefore aimed to elucidate the role of myeloid PHD2, the dominant PHD isoform, on intraplaque angiogenesis in a murine model for venous bypass grafting.
METHODS AND RESULTS RESULTS
Myeloid PHD2 conditional knockout (PHD2cko) and PHD2 wild type mice on an Ldlr
CONCLUSIONS CONCLUSIONS
Myeloid PHD2cko reduces vein graft disease and ameliorates vein graft lesion stability by improving intraplaque angiogenesis.

Identifiants

pubmed: 38258662
doi: 10.1161/JAHA.123.033109
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e033109

Auteurs

Thijs J Sluiter (TJ)

Department of Surgery Leiden University Medical Centre Leiden The Netherlands.
Einthoven Laboratory for Experimental Vascular Medicine Leiden University Medical Centre Leiden The Netherlands.

Renée J H A Tillie (RJHA)

Department of Pathology, CARIM School for Cardiovascular Sciences Maastricht University Medical Centre Maastricht The Netherlands.

Alwin de Jong (A)

Department of Surgery Leiden University Medical Centre Leiden The Netherlands.
Einthoven Laboratory for Experimental Vascular Medicine Leiden University Medical Centre Leiden The Netherlands.

Jenny B G de Bruijn (JBG)

Department of Pathology, CARIM School for Cardiovascular Sciences Maastricht University Medical Centre Maastricht The Netherlands.

Hendrika A B Peters (HAB)

Department of Surgery Leiden University Medical Centre Leiden The Netherlands.
Einthoven Laboratory for Experimental Vascular Medicine Leiden University Medical Centre Leiden The Netherlands.

Remco van de Leijgraaf (R)

Department of Surgery Leiden University Medical Centre Leiden The Netherlands.

Raghed Halawani (R)

Department of Surgery Leiden University Medical Centre Leiden The Netherlands.

Michelle Westmaas (M)

Department of Surgery Leiden University Medical Centre Leiden The Netherlands.

Lineke I W Starink (LIW)

Department of Surgery Leiden University Medical Centre Leiden The Netherlands.

Paul H A Quax (PHA)

Department of Surgery Leiden University Medical Centre Leiden The Netherlands.
Einthoven Laboratory for Experimental Vascular Medicine Leiden University Medical Centre Leiden The Netherlands.

Judith C Sluimer (JC)

Department of Pathology, CARIM School for Cardiovascular Sciences Maastricht University Medical Centre Maastricht The Netherlands.
Centre for Cardiovascular Sciences University of Edinburgh Edinburgh United Kingdom.

Margreet R de Vries (MR)

Department of Surgery Leiden University Medical Centre Leiden The Netherlands.
Einthoven Laboratory for Experimental Vascular Medicine Leiden University Medical Centre Leiden The Netherlands.
Department of Surgery Brigham and Women's Hospital, Harvard Medical School Boston MA.

Classifications MeSH