P2Y11 Agonism Prevents Hypoxia/Reoxygenation- and Angiotensin II-Induced Vascular Dysfunction and Intimal Hyperplasia Development
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...
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MDPI AG
2021-01-01
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| Series: | International Journal of Molecular Sciences |
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| author | Marie Piollet Adrian Sturza Stéphanie Chadet Claudie Gabillard-Lefort Lauriane Benoist Danina-Mirela Muntean Oana-Maria Aburel Denis Angoulvant Fabrice Ivanes |
| author_facet | Marie Piollet Adrian Sturza Stéphanie Chadet Claudie Gabillard-Lefort Lauriane Benoist Danina-Mirela Muntean Oana-Maria Aburel Denis Angoulvant Fabrice Ivanes |
| author_sort | Marie Piollet |
| collection | DOAJ |
| description | 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 H<sub>2</sub>O<sub>2</sub> 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. |
| first_indexed | 2024-03-09T04:34:45Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T04:34:45Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-45a782d0e7674acea390fb0de23492292023-12-03T13:29:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-0122285510.3390/ijms22020855P2Y11 Agonism Prevents Hypoxia/Reoxygenation- and Angiotensin II-Induced Vascular Dysfunction and Intimal Hyperplasia DevelopmentMarie Piollet0Adrian Sturza1Stéphanie Chadet2Claudie Gabillard-Lefort3Lauriane Benoist4Danina-Mirela Muntean5Oana-Maria Aburel6Denis Angoulvant7Fabrice Ivanes8EA4245 Transplantation, Immunology and Inflammation Laboratory, Loire Valley Cardiovascular Collaboration, University of Tours, 37000 Tours, FranceDepartment of Functional Sciences-Pathophysiology, Center for Translational Research and Systems Medicine, “Victor Babeș” University of Medicine and Pharmacy Timișoara, 300041 Timișoara, RomaniaEA4245 Transplantation, Immunology and Inflammation Laboratory, Loire Valley Cardiovascular Collaboration, University of Tours, 37000 Tours, FranceEA4245 Transplantation, Immunology and Inflammation Laboratory, Loire Valley Cardiovascular Collaboration, University of Tours, 37000 Tours, FranceEA4245 Transplantation, Immunology and Inflammation Laboratory, Loire Valley Cardiovascular Collaboration, University of Tours, 37000 Tours, FranceDepartment of Functional Sciences-Pathophysiology, Center for Translational Research and Systems Medicine, “Victor Babeș” University of Medicine and Pharmacy Timișoara, 300041 Timișoara, RomaniaDepartment of Functional Sciences-Pathophysiology, Center for Translational Research and Systems Medicine, “Victor Babeș” University of Medicine and Pharmacy Timișoara, 300041 Timișoara, RomaniaEA4245 Transplantation, Immunology and Inflammation Laboratory, Loire Valley Cardiovascular Collaboration, University of Tours, 37000 Tours, FranceEA4245 Transplantation, Immunology and Inflammation Laboratory, Loire Valley Cardiovascular Collaboration, University of Tours, 37000 Tours, FranceVascular 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 H<sub>2</sub>O<sub>2</sub> 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.https://www.mdpi.com/1422-0067/22/2/855cardiovascular protectionP2Y purinoreceptorvascular dysfunctionischemia reperfusion injury |
| spellingShingle | Marie Piollet Adrian Sturza Stéphanie Chadet Claudie Gabillard-Lefort Lauriane Benoist Danina-Mirela Muntean Oana-Maria Aburel Denis Angoulvant Fabrice Ivanes P2Y11 Agonism Prevents Hypoxia/Reoxygenation- and Angiotensin II-Induced Vascular Dysfunction and Intimal Hyperplasia Development International Journal of Molecular Sciences cardiovascular protection P2Y purinoreceptor vascular dysfunction ischemia reperfusion injury |
| title | P2Y11 Agonism Prevents Hypoxia/Reoxygenation- and Angiotensin II-Induced Vascular Dysfunction and Intimal Hyperplasia Development |
| title_full | P2Y11 Agonism Prevents Hypoxia/Reoxygenation- and Angiotensin II-Induced Vascular Dysfunction and Intimal Hyperplasia Development |
| title_fullStr | P2Y11 Agonism Prevents Hypoxia/Reoxygenation- and Angiotensin II-Induced Vascular Dysfunction and Intimal Hyperplasia Development |
| title_full_unstemmed | P2Y11 Agonism Prevents Hypoxia/Reoxygenation- and Angiotensin II-Induced Vascular Dysfunction and Intimal Hyperplasia Development |
| title_short | P2Y11 Agonism Prevents Hypoxia/Reoxygenation- and Angiotensin II-Induced Vascular Dysfunction and Intimal Hyperplasia Development |
| title_sort | p2y11 agonism prevents hypoxia reoxygenation and angiotensin ii induced vascular dysfunction and intimal hyperplasia development |
| topic | cardiovascular protection P2Y purinoreceptor vascular dysfunction ischemia reperfusion injury |
| url | https://www.mdpi.com/1422-0067/22/2/855 |
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