Fig. 2

Z-stack images of vessels double-labeled for the endothelial marker Ulex europaeus lectin (UEA-l, brown) and collagen IV (COLL4, blue) in 100 μm thick sections. a-b In healthy vessels (type 1), COLL4-positive membranes are only visible in areas with bubble-shaped expansions (arrows) as seen in a control case without SVD (NoSVD). Small endothelial indentations are also found in healthy vessels (star; type 2a), which have COLL4-positive basement membranes with smooth contours (see Fig. 6b for comparison with type 2b vessel). c-d COLL4- positive basement membranes of small vessels are often barely distinguishable from the staining of the endothelium (labeled with UEA-l) in healthy vessels (inset in c) in thick sections except in vessel segments with vascular bags. Vascular bags (arrows) are formed by external COLL4-positive membranes detached from the vessel wall. In NoSVD controls they are usually limited to short vessel segments (type 3a, see c), whereas in SVD they can cover long distances (type 3b, see d). e-f Severely diseased vessels (type 4) show both endothelial irregularities (open arrow heads) and vascular bagging with thickened basement membranes (small black arrow head). Vascular bagging can extend over considerable distances in type 4 vessels with various diameters (arrows) in SVD. Double arrows indicate multiple layers of collagenous membranes. Images obtained from Case 1 (myocardial infarction, NoSVD) (a-b), Case 2 (ovarian cancer, NoSVD) (c-d), and Case 6 (non-hodgkin lymphoma, pure SVD) (e-f). For viewing vascular bags, also see Additional file 2: Video S1 of Vessels. Scale bars 50 μm