NTPDase1/CD39 Ectonucleotidase Is Necessary for Normal Arterial Diameter Adaptation to Flow.
Julie FavreCharlotte RoyAnne-Laure GuihotAnnick DrouinManon LapriseMarc-Antoine GillisSimon C RobsonEric ThorinJean SévignyHenrion DanielGilles KauffensteinPublished in: International journal of molecular sciences (2023)
NTPDase1/CD39, the major vascular ectonucleotidase, exerts thrombo-immunoregulatory function by controlling endothelial P2 receptor activation. Despite the well-described release of ATP from endothelial cells, few data are available regarding the potential role of CD39 as a regulator of arterial diameter. We thus investigated the contribution of CD39 in short-term diameter adaptation and long-term arterial remodeling in response to flow using Entpd1 -/- male mice. Compared to wild-type littermates, endothelial-dependent relaxation was modified in Entpd1 -/- mice. Specifically, the vasorelaxation in response to ATP was potentiated in both conductance (aorta) and small resistance (mesenteric and coronary) arteries. By contrast, the relaxing responses to acetylcholine were supra-normalized in thoracic aortas while decreased in resistance arteries from Entpd1 -/- mice. Acute flow-mediated dilation, measured via pressure myography, was dramatically diminished and outward remodeling induced by in vivo chronic increased shear stress was altered in the mesenteric resistance arteries isolated from Entpd1 -/- mice compared to wild-types. Finally, changes in vascular reactivity in Entpd1 -/- mice were also evidenced by a decrease in the coronary output measured in isolated perfused hearts compared to the wild-type mice. Our results highlight a key regulatory role for purinergic signaling and CD39 in endothelium-dependent short- and long-term arterial diameter adaptation to increased flow.
Keyphrases
- wild type
- endothelial cells
- high fat diet induced
- coronary artery disease
- nk cells
- optic nerve
- magnetic resonance
- coronary artery
- risk assessment
- insulin resistance
- type diabetes
- intensive care unit
- adipose tissue
- machine learning
- single molecule
- computed tomography
- human health
- acute respiratory distress syndrome
- pulmonary arterial hypertension
- blood flow
- binding protein
- mass spectrometry
- mechanical ventilation