Model characteristics at 15 months of follow up.

<p>Model characteristics at 15 months of follow up.</p

Early stages of atherogenic DM leads to renal damage.

<p>A: Representative illustration of PAS stained glomeruli from a DM+ATH pig, showing mesangial proliferation and matrix expansion with capillary loops lying around the mesangium as a corona, reminiscent of a beginning Kimmelstiel-Wilson nodule (left panel; thin black arrow). Dilated capillary loops with red cell fragments show intense PAI-1 staining on consecutive slides (right panel; thick black arrow). B: Mesangial expansion index in Controls (n = 7), ATH (n = 5) and DM+ATH (n = 5) pigs. C. Electron microscopy images illustrating a normal GBM architecture (left panel; thick arrow) of the Controls pig. In ATH, there is slight effacement of the podocyte pedicles (middle panel; thick arrow). In DM+ATH, marked lipid deposits were found (right panel). Data are shown as mean ± SEM. *P<0.05 compared to Controls or ATH pigs. Original magnification of A: x400 and C: x8000.</p

No difference in renal vWf and VEGF-A expression.

<p>A. Representative illustrations of kidney sections stained with endothelial marker vWF (arrow: glomerulus; arrowhead: peritubular area) in Controls, ATH, and DM+ATH pigs. B. Representative images of kidney sections stained with VEGF in Controls, ATH, and DM+ATH pigs showing expression in podocytes (arrow head), parietal epithelial cells (thin arrow) and tubuli (asterix). Original magnification of A: x 200 and B: x400.</p

Correlation between capillary tortuosity and Angpt2/Angpt1balance and creatinine levels.

<p>Scatter plot showing the correlation of renal protein expression of Angpt1(A), Angpt2 (B), Angpt2/Angpt1ratio (C).</p

QCA and OCT analysis results.

<p><b>A+B</b>) Mean lumen diameter (LD) slightly increased from pre-to post-implantation, decreased from post-implantation to 3M and remained stable from 3M to 6M. Grey: FF-DM, black: FF-NDM. <b>C-E</b>) Mean lumen area (LA), lumen diameter (LD) and minimal lumen diameter (MLD) increased slightly from pre- to post-implantation. Mean LA, LD and MLD and mean scaffold area (SA) and scaffold diameter (SD) decreased from post-implantation to 3M and mean LA, LD, MLD, SA, SD and coverage area (CA) remained stable from 3M to 6M. <b>F</b>) Proximal and distal reference LA slightly decrease from pre- to post-implantation and stabilized from post-implantation to 3M and 6M.</p

Study design.

<p>BVS = bioresorbable vascular scaffold, FUP = follow-up, QCA = quantitative coronary angiography, PS = Polarization Sensitive, OCT = optical coherence tomography, NIRS = near-infrared spectroscopy, GPC = gel permeation chromatography.</p

(PS)-OCT and corresponding histology at 6M.

<p>OCT demonstrated the development of a highly heterogeneous neointima with lipid and calcium accumulation in FF-DM and FF-NDM swine at 6 months (<b>A, L</b>), which was confirmed by histology (<b>D, I, O, S</b>; Oil-red-O). Phase retardation corresponding to tissue birefringence (<b>B, M</b>) and depolarization (<b>G, Q</b>) imaged by PS-OCT, demonstrated enhanced birefringence and depolarization (<b>C</b>) in an SMC-poor area (<b>E</b>; aSMA) with inflammation (<b>F</b>; CD45). Furthermore, PS-OCT demonstrated focal depolarization (<b>H</b>) in a collagen-poor area with loss of structure and evidence of early necrosis (<b>J, K</b>; HE, PSR). <b>N</b> shows coarse-grained high birefringence in an area with strongly circumferentially organized intimal SMCs (<b>P</b>; RF); lipid-rich, SMC-poor tissue (<b>T</b>; SMA) exhibits a more finely speckled heterogeneity, associated with a rapid loss of polarization degree (<b>R</b>). Asterisk (*) indicates guidewire artefact, arrowheads lipid, white lines calcium.</p

Corresponding QCA, OCT, NIRS and histology at 6M.

<p>QCA (<b>A</b>) demonstrates the scaffolded region (white block), with the yellow line indicating the region corresponding to the NIRS, (PS)-OCT and histology images (<b>B-G</b>). The NIRS chemogram demonstrates presence of lipid (<b>B</b>), also observed by OCT (<b>D</b>; arrowheads) that additionally demonstrates the presence of calcium (white circles). The PS-OCT phase retardation image demonstrates a finely grained pattern (<b>E</b>) consistent with lipid-rich neointima (<b>F</b>; Oil-Red-O) and active inflammation (<b>G</b>; CD45).</p

Irregular collagen distribution in the neointima.

<p>Collagen poor areas in peri-strut regions and neointima (<b>A, D</b>; Picrosirius Red) often demonstrated lipid accumulation (<b>B, E</b>; Oil-red-O), and leucocytes (<b>C, F</b>; CD45). Additionally, <b>G</b> (Picrosirius Red) demonstrates a patchy collagen poor lesion with lipid accumulation (<b>H</b>; Oil-red-O) and smooth muscle cells (<b>I</b>; aSMA). *: strut void, <b>L</b>: lumen.</p

GPC and histology results.

<p>GPC and histology results.</p