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- W764897612 abstract "Objective Type 2 diabetes is associated with microvascular dysfunction. We hypothesized that increased Poly-(ADP-ribose) polymerase 1 (PARP-1) activity contributes to coronary arteriolar dysfunction. Methods and Results Type 2 diabetic db−/db− (diabetic) and non-diabetic db−/db+ (control) mice were treated with PARP-1 inhibitors (INO-1001, 5mg/Kg/day and ABT-888, 15mg/Kg/day) for two weeks. Isolated coronary arterioles were mounted in an arteriograph. Pressure-induced myogenic tone (MT) was significantly potentiated, while endothelium-dependent relaxation was significantly attenuated in diabetic mice compared to control. These results are associated with increased PARP-1 activity in coronary arterioles from diabetic mice compared to control. Interestingly, diabetic mice treated by PARP-1 inhibitors significantly reduced the potentiation of myogenic tone and improved the endothelium-dependent relaxation. Down regulation of PARP-1 in coronary arterioles using lentivirus-shRNA-PARP-1 significantly improved coronary arteriole function in diabetic mice compared to control. The inhibition of nitric oxide synthesis by L-NAME significantly reduced the endothelium-dependent relaxation in coronary arterioles from sham and diabetic mice treated with PARP-1 inhibitors and lentivirus-shRNA-PARP-1. Conclusions We provide evidence of a link between the increased PARP-1 activity and coronary arteriole dysfunction in type 2 diabetic mice. Thus, PARP-1 may be a potential target for overcoming diabetic microvessels complications." @default.
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- W764897612 date "2011-04-01" @default.
- W764897612 modified "2023-09-27" @default.
- W764897612 title "PARP‐1 inhibition improves coronary arteriole function in type 2 diabetic mice" @default.
- W764897612 doi "https://doi.org/10.1096/fasebj.25.1_supplement.1025.9" @default.
- W764897612 hasPublicationYear "2011" @default.
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