The effect of bioresorbable vascular scaffold implantation on distal coronary endothelial function in dyslipidemic swine with and without diabetes Mieke.

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The effect of bioresorbable vascular scaffold implantation on distal coronary endothelial function in dyslipidemic swine with and without diabetes Mieke van den Heuvel, Oana Sorop, Nienke S. van Ditzhuijzen, René de Vries, Richard W.B. van Duin, Ilona Peters, Janine E. van Loon, Moniek P. de Maat, Heleen M. van Beusekom, Wim J. van der Giessen, A.H. Jan Danser, Dirk J. Duncker International Journal of Cardiology Volume 252, Pages 44-51 (February 2018) DOI: 10.1016/j.ijcard.2017.11.037 Copyright © 2017 Terms and Conditions

Fig. 1 Representative angiogram with depicted vessel segments located >5mm proximal (delineated by the dashed white lines A--A) and distal (delineated by the dashed red lines C--C) to the BVS edges (delineated by the dashed yellow lines B--B), or corresponding segments of the reference (control) artery from which the mean lumen diameters were calculated (panel A). Two representative segments (opened longitudinally), showing macroscopic fatty streaks, as visualized by en face Oil-red-O staining (panel B), and representative cross-sections (resorcin-fuchsin staining) showing plaques with different degrees of complexity from DM+HFD (panels C–J) and HFD (panels K–S) swine. ⁎Indicates plaque. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.) International Journal of Cardiology 2018 252, 44-51DOI: (10.1016/j.ijcard.2017.11.037) Copyright © 2017 Terms and Conditions

Fig. 2 Detailed coronary conduit function located >5mm distal to the BVS and in control arteries, in dyslipidemic swine with or without DM. Figure highlighting the effects of six months of BVS implantation on BK-mediated vasodilation (A, D), SNAP-mediated vasodilation (B, E), and ET-1 mediated vasoconstriction (C, F) of distal conduit segments of DM+HFD (A-C) and HFD swine (D-F). Figure also highlighting the effect of DM+HFD on conduit arterial function of control segments (A–C) vs. HFD control segments (D–F). ⁎p<0.01 DM+HFD BVS vs. DM+HFD Control; †p=0.051 DM+HFD Control vs. HFD Control. BK=bradykinin, BVS=bioresorbable vascular scaffold, DM=diabetes mellitus, ET-1=endothelin-1, HFD=high fat diet, n=number of animals, SNAP=S-nitroso-N-acetylpenicillamine. International Journal of Cardiology 2018 252, 44-51DOI: (10.1016/j.ijcard.2017.11.037) Copyright © 2017 Terms and Conditions

Fig. 3 NO- and non NO-mediated endothelial function located >5mm distal to the BVS and in control arteries, in dyslipidemic swine with or without DM. Figure highlighting the effects of six months of BVS implantation on NO-mediated endothelium dependent vasodilation of distal conduit segments of DM+HFD (A, B) and HFD swine (C, D). The grey area in between the BK and l-NAME curves depicts the specific contribution of the NO-mediated component of the BK-response. ⁎p<0.05 area DM+HFD BVS vs. area DM+HFD Control; †p<0.05 area DM+HFD BVS vs. area HFD BVS; ‡p<0.05 BK vs. BK+l-NAME. Abbreviations as in Fig. 2. In addition: l-NAME=N-nitro-l-arginine methyl ester, NO=nitric oxide. International Journal of Cardiology 2018 252, 44-51DOI: (10.1016/j.ijcard.2017.11.037) Copyright © 2017 Terms and Conditions

Fig. 4 Detailed coronary small arterial function in the distal perfusion area of the BVS and in control segments, in dyslipidemic swine with or without DM. Figure highlighting the effects of BVS on endothelium-dependent BK-induced vasodilation (A, E) after specific blockers (B, C, D, F, G, H), as well as endothelium-independent SNAP-induced vasodilation (I, J) and ET-1-induced vasoconstriction (K, L) of segments from the distal coronary microcirculation of DM+HFD (A, B, C, D, I, K) and HFD swine (E, F, G, H, J, L). Figure also highlighting the effect of DM+HFD on BK-mediated small arterial function distal to BVS (A) vs. BVS-treated vessels of HFD swine (E). l-NAME: blockage of endogenous NO (B, F). TRAM+APA: blockage of specific EDHFs (C, G). l-NAME+TRAM+APA: blockage of both endogenous NO and of specific EDHFs (D, H). ⁎p<0.01 DM+HFD BVS vs. DM+HFD Control; †p<0.05 DM+HFD BVS vs. DM+HFD Control; ‡p<0.01 DM+HFD BVS vs. HFD BVS. Abbreviations as in Fig. 2. In addition: EDHF=endothelium-derived hyperpolarizing factor, TRAM+APA=TRAM34 and apamin. International Journal of Cardiology 2018 252, 44-51DOI: (10.1016/j.ijcard.2017.11.037) Copyright © 2017 Terms and Conditions