P2Y11 Agonism Prevents Hypoxia/Reoxygenation- and Angiotensin II-Induced Vascular Dysfunction and Intimal Hyperplasia Development

Autor: Stéphanie Chadet, Marie Piollet, Claudie Gabillard-Lefort, Fabrice Ivanes, Oana-Maria Aburel, Lauriane Benoist, Denis Angoulvant, Danina-Mirela Muntean, Adrian Sturza
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Intimal hyperplasia
030204 cardiovascular system & hematology
Pharmacology
lcsh:Chemistry
chemistry.chemical_compound
0302 clinical medicine
Naphthalenesulfonates
Enos
Receptor
lcsh:QH301-705.5
Aorta
Spectroscopy
ischemia reperfusion injury
Diphosphonates
Endothelin-1
biology
Angiotensin II
General Medicine
vascular dysfunction
Computer Science Applications
Vasodilation
P2Y purinoreceptor
Reperfusion Injury
cardiovascular system
cardiovascular protection
medicine.symptom
Purinergic P2 Receptor Agonists
Agonist
Nitric Oxide Synthase Type III
medicine.drug_class
Myocytes
Smooth Muscle
Nitric Oxide
Article
Catalysis
Nitric oxide
Inorganic Chemistry
03 medical and health sciences
Human Umbilical Vein Endothelial Cells
medicine
Animals
Humans
Rats
Wistar
Physical and Theoretical Chemistry
Molecular Biology
Hyperplasia
Receptors
Purinergic P2
business.industry
Organic Chemistry
Antagonist
Water
Hypoxia (medical)
biology.organism_classification
medicine.disease
Rats
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
chemistry
Tunica Intima
business
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 855, p 855 (2021)
International Journal of Molecular Sciences
Volume 22
Issue 2
ISSN: 1422-0067
DOI: 10.3390/ijms22020855
Popis: Vascular dysfunction in cardiovascular diseases includes vasomotor response impairments, endothelial cells (ECs) activation, and smooth muscle cells (SMCs) proliferation and migration to the intima. This results in intimal hyperplasia and vessel failure. We previously reported that activation of the P2Y11 receptor (P2Y11R) in human dendritic cells, cardiofibroblasts and cardiomyocytes was protective against hypoxia/reoxygenation (HR) lesions. In this study, we investigated the role of P2Y11R signaling in vascular dysfunction. P2Y11R activity was modulated using its pharmacological agonist NF546 and antagonist NF340. Rat aortic rings were exposed to angiotensin II (AngII) and evaluated for their vasomotor response. The P2Y11R agonist NF546 reduced AngII-induced vascular dysfunction by promoting EC-dependent vasorelaxation, through an increased nitric oxide (NO) bioavailability and reduced AngII-induced H2O2 release
these effects were prevented by the use of the P2Y11R antagonist NF340. Human vascular SMCs and ECs were subjected to AngII or H/R simulation in vitro. P2Y11R agonist modulated vasoactive factors in human ECs, that is, endothelial nitric oxide synthase (eNOS) and endothelin-1, reduced SMC proliferation and prevented the switch towards a synthetic phenotype. H/R and AngII increased ECs secretome-induced SMC proliferation, an effect prevented by P2Y11R activation. Thus, our data suggest that P2Y11R activation may protect blood vessels from HR-/AngII-induced injury and reduce vascular dysfunctions. These results open the way for new vasculoprotective interventions.
Databáze: OpenAIRE
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