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0229 : Aerobic exercise training modulates microparticles miRNAs: link to improved endothelial function and regulation of inflammation?
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Archives of Cardiovascular Diseases Supplements (2016) 8, 250-251
Here, we sought to establish : i) respective contributions of PDE3 and PDE4 families in regulating tone of rat coronary arteries (CA) under various cAMP stimuli; ii) the particular role of BK Ca channels under these stimuli. Methods CA were isolated from adult male Wistar rats. Responses to vasodilators were studied on CA rings mounted on a small vessel myograph and contracted with thromboxane analogue U46619. cAMP-PDE activity was measured in CA lysate using a radioenzymatic assay. Contributions of PDE3 and PDE4 were studied using selective inhibitors, namely Ro 20-1724 (Ro, 10 μM) and cilostamide (Cil, 1 μM). Role of BKCa channels was studied using the specific blocker iberiotoxin (IBTX, 100 nM). Results Contributions of PDE3 and PDE4 to the total cAMP hydrolysing activity in rat CA were 55±5% and 31±2%, respectively. Addition of Ro or Cil on contracted CA induced relaxations that were strongly blunted in the presence of IBTX. Ro and Cil potentiated relaxant responses to increasing concentrations of cAMP-elevating agents, namely β-adrenergic receptor agonist isoproterenol (ISO) or the forskolin analogue L858051 (L85), a direct activator of cAMP production. IBTX shifted to the right the relaxant response to L85 whereas it reduced maximal response to ISO. Interestingly, IBTX blocked the potentiating effect of Ro on ISO response, but not on L85 response. By contrast, BKCa inhibition neither prevented potentiation of ISO nor L85 responses by Cil. Conclusion Our data suggest that, in rat CA, the contribution of BKCa channels to the relaxant effects of PDE3 and PDE4 inhibition varies depending on the mode of cAMP stimulation. The author hereby declares no conflict of interest
0229 Aerobic exercise training modulates microparticles miRNAs: link to improved endothelial function and regulation of inflammation? Saloua Dimassi (1), Esma Karkeni (2), Karim Chahed (3), Soumaya Boumiza (3), Zouhair Tabka (3), Pascal Laurant (1), Jean-François Landrier (2), Catherine Riva * (1) (1) Université d'Avignon, Avignon, France – (2) Université d’Aix-Marseille, Marseille, France – (3) Faculté de Médecine de Sousse, Sousse, Tunisie * Corresponding author: [email protected] (Catherine Riva) Exercise training is known to stimulate vascular function and remodeling in a shear stress and inflammation dependent manner. Microparticles (MPs) released from vascular cells in response to shear stress, play a role in cell-cell crosstalk through carrying bioactive molecules such as miRNAs. Thus, the aim of our study was to explore whether exercise training impacts vascular wall cells and contributes to vascular function improvement through the modulation of inflammation molecules release. Therefore, we investigated the presence in MPs of 9 inflammation-regulatory miRNAs. A group of sedentary women (n=6, BMI<25Kg/m²) recruited at F. Hached Hospital (Sousse, Tunisia) was enrolled in an 8-weeks training program. Vascular function was assessed by Laser Doppler Flowmetry, oxidant stress and systemic inflammatory marker (CRPus) and selected circulating cytokines were measured. Furthermore, before and after exercise training, circulating MPs quantification by flow cytometry and miRNAs content by real-time PCR, were realized. While exercise training improved significantly the endothelial-dependent vasorelaxation, decreased systemic inflammation and modified the profile of circulating cytokines, circulating MPs level and oxidant stress remained unchanged. The miRNAs profile revealed that 1/ miR155 and miR302a were not detected in MPs neither before nor after training program; 2/ miR21, miR150, miR320a, miR146a, miR124a, miR126 and miR223 were expressed in circulating MPs of sedentary women; and 3/ after training program, a significant increase of miR21, miR146a, miR124a, miR150 and miR223 content was observed while miR126 and miR223 remained unchanged. Our results highlight the role of MPs as vehicle for miRNAs and the importance of inflammation-regulatory miRNAs as effectors in the vascular wall in order to generate an optimal vascular function and to control inflammation. The author hereby declares no conflict of interest
© Elsevier Masson SAS. All rights reserved.
Archives of Cardiovascular Diseases Supplements (2016) 8, 250-251
Here, we sought to establish : i) respective contributions of PDE3 and PDE4 families in regulating tone of rat coronary arteries (CA) under various cAMP stimuli; ii) the particular role of BK Ca channels under these stimuli. Methods CA were isolated from adult male Wistar rats. Responses to vasodilators were studied on CA rings mounted on a small vessel myograph and contracted with thromboxane analogue U46619. cAMP-PDE activity was measured in CA lysate using a radioenzymatic assay. Contributions of PDE3 and PDE4 were studied using selective inhibitors, namely Ro 20-1724 (Ro, 10 μM) and cilostamide (Cil, 1 μM). Role of BKCa channels was studied using the specific blocker iberiotoxin (IBTX, 100 nM). Results Contributions of PDE3 and PDE4 to the total cAMP hydrolysing activity in rat CA were 55±5% and 31±2%, respectively. Addition of Ro or Cil on contracted CA induced relaxations that were strongly blunted in the presence of IBTX. Ro and Cil potentiated relaxant responses to increasing concentrations of cAMP-elevating agents, namely β-adrenergic receptor agonist isoproterenol (ISO) or the forskolin analogue L858051 (L85), a direct activator of cAMP production. IBTX shifted to the right the relaxant response to L85 whereas it reduced maximal response to ISO. Interestingly, IBTX blocked the potentiating effect of Ro on ISO response, but not on L85 response. By contrast, BKCa inhibition neither prevented potentiation of ISO nor L85 responses by Cil. Conclusion Our data suggest that, in rat CA, the contribution of BKCa channels to the relaxant effects of PDE3 and PDE4 inhibition varies depending on the mode of cAMP stimulation. The author hereby declares no conflict of interest
0229 Aerobic exercise training modulates microparticles miRNAs: link to improved endothelial function and regulation of inflammation? Saloua Dimassi (1), Esma Karkeni (2), Karim Chahed (3), Soumaya Boumiza (3), Zouhair Tabka (3), Pascal Laurant (1), Jean-François Landrier (2), Catherine Riva * (1) (1) Université d'Avignon, Avignon, France – (2) Université d’Aix-Marseille, Marseille, France – (3) Faculté de Médecine de Sousse, Sousse, Tunisie * Corresponding author: [email protected] (Catherine Riva) Exercise training is known to stimulate vascular function and remodeling in a shear stress and inflammation dependent manner. Microparticles (MPs) released from vascular cells in response to shear stress, play a role in cell-cell crosstalk through carrying bioactive molecules such as miRNAs. Thus, the aim of our study was to explore whether exercise training impacts vascular wall cells and contributes to vascular function improvement through the modulation of inflammation molecules release. Therefore, we investigated the presence in MPs of 9 inflammation-regulatory miRNAs. A group of sedentary women (n=6, BMI<25Kg/m²) recruited at F. Hached Hospital (Sousse, Tunisia) was enrolled in an 8-weeks training program. Vascular function was assessed by Laser Doppler Flowmetry, oxidant stress and systemic inflammatory marker (CRPus) and selected circulating cytokines were measured. Furthermore, before and after exercise training, circulating MPs quantification by flow cytometry and miRNAs content by real-time PCR, were realized. While exercise training improved significantly the endothelial-dependent vasorelaxation, decreased systemic inflammation and modified the profile of circulating cytokines, circulating MPs level and oxidant stress remained unchanged. The miRNAs profile revealed that 1/ miR155 and miR302a were not detected in MPs neither before nor after training program; 2/ miR21, miR150, miR320a, miR146a, miR124a, miR126 and miR223 were expressed in circulating MPs of sedentary women; and 3/ after training program, a significant increase of miR21, miR146a, miR124a, miR150 and miR223 content was observed while miR126 and miR223 remained unchanged. Our results highlight the role of MPs as vehicle for miRNAs and the importance of inflammation-regulatory miRNAs as effectors in the vascular wall in order to generate an optimal vascular function and to control inflammation. The author hereby declares no conflict of interest
© Elsevier Masson SAS. All rights reserved.