Vascular intima

Based on postmortem findings in a 32-year-old woman who died with an acute encephalopathy (30) and another report of two patients investigated with tran-scranial Doppler ultrasound and MRI for symptoms of ciclosporin nenrotoxicity (31), vascular changes with vasospasm and dissection of the vascular intima strongly snggest that vascnlopathy is a possible mechanism of ciclosporin-indnced encephalopathy. 

The normal arterial wall consists of the intima, media, and adventitia, as illustrated in Fig. 4—3A. The endothelium is located in the intima and consists of a layer of endothelial cells that line the lumen of the artery and form a selective barrier between the vessel wall and blood contents. The internal elastic lamina separates the intima and media, where vascular smooth muscle cells are found. The vascular adventitia comprises the artery s outer layer. Atherosclerotic lesions form in the subendothelial space between the endothelial cells and internal elastic lamina. 

Geng, Y.J., Henderson, L.E., levesque, E.B., Muszynski, M., and Libby, P., 1997, Fas is expressed in human atherosclerotic intima and promotes apoptosis of cytokine-primed human vascular smooth muscle cells, Arterioscler. Thromb. Vase. Biol. 17 2200-2208. 

Figure 26. Reconstruction of the tunica intima on the inner surface of a clinically used polyethylene terephtalate vascular prosthesis. A non-modified inner surface of the prosthesis, B immobilization of defined assemblies of protein molecules (e.g., collagenfiarninin or collagen+fibrin) on the inner surface of the graft, C immunofluorescence of von Willebrand factor, a marker of the identity a differentiation of vascular endothelial cells, in human saphenous vein endothelial cells in cultures on the inner surface of a prosthesis coated with collagen and larninin, D detail of a layer of endothelial cells growing on a layer of collagen and fibrin. Note well developed talin-containing focal adhesion plaques. A, B conventional optical microscope, C, D confocal microscope Leica DM 2500 [30,31].

Fibrosis resulting in the loss of normal organ structures is the hallmark of chronic rejection. The fibrosis may be due to wound healing, which is then followed by the cellular necrosis of acute rejection. However, it must be pointed out that chronic rejection develops many times in the absence of acute rejection. Fibrosis may be a result of several diverse factors such as equation of chronic rejection with chronic delayed-type hypersensitivity reaction, injury to blood vessels and resulting response to chronic ischemia, the proliferation of smooth muscle cells in the intima of arterial walls producing vascular occlusion, or persistent viral infections that will induce cellular immune response. 

Furthermore, there is a direct correlation between the paclitaxel dose delivered to the artery and the vascular response when examined in the porcine coronary artery model. The slow-release formulation demonstrated patent lumen, struts covered by stable intima and re-endothelializa-tion with minimal fibrin, whereas the fast-release formulation resulted in noticeable fibrin accumulation, an indication of higher level of drug exposure to the arteries (Fig. 10). It should be noted that the 8.8% slow-release formulation is currently marketed as TAXUS SR and has demonstrated efficacy in clinical studies this is discussed in the next section. 

Note. Results are mean SD. No significant differences Abbreviation VEGF, vascular endothelial growth factor. Source From Ref. 24. are seen between the two groups, including the intima/media ratio. ... 

These differences in the prostaglandins synthesised in endothelium and platelets are important. Intact vascular endothelium does not activate platelets because of the high concentration of prostacyclin in the intima. Subintimal tissues contain little prostacyclin and platelets, under the influence of thromboxane-Aj, immediately adhere and aggregate at any breach in the intima. Atheromatous plaques do not generate prostacyclin—which explains platelet adhesion and thrombosis at these sites. 

---