Neointimal hyperplasia

Rogers C, Welt EG, Kamovsky MJ, Edelman ER. Monocyte recruitment and neointimal hyperplasia in rabbits. Coupled inhibitory effects of heparin. Arterioscler Thromb Vase Biol 1996 16 1312-1318. 

Danenberg HD, Golomb G, Groothuis A, et al. Liposomal alendronate inhibits systemic innate immunity and reduces instent neointimal hyperplasia in rabbits. Circulation 2003 108 2798-2804. 

Wang Y, Wang J, Ean Q, Geng J. (2007) Andrographolide inhibits NF-kB activation and attenuates neointimal hyperplasia in arterial restinosis. Cell Res 17 933-941. 

Kornowski R, Hong MK, Tio FO, Bramwell O, Wu H, Leon MB. In-stent restenosis contributions of inflammatory responses and arterial injury to neointimal hyperplasia. J Am Coll Cardiol 1998 31 224-230. 

Morishita, R., Gibbons, G.H., Ellison, K.E., et al. (1993). Single intraluminal delivery of antisense cdc2 kinase and proliferating-cell nuclear antigen oligonucleotides results in chronic inhibition of neointimal hyperplasia. Proc. Natl. Acad. Sci. U.S.A., 90, 8474-8478. 

Recent evidence suggests that atherosclerosis is a chronic inflammatory process. The recruitment of mononuclear leukocytes and formation of intimal macrophage-rich lesions at specific sites of the arterial tree are key events in atherogenesis. Alterations of chemotactic and adhesive properties of the endothelium play an important role in this process [82]. Quercetin has been reported to inhibit the expression in glomerular cells of monocyte chemoattractant protein-1 (MCP-1) [83] a potent chemoattractant for circulating monocytes. Red wine reduced MCP-1 mRNA and protein expression in abdominal aorta of cholesterol fed rabbits after balloon injury and this effect was associated with a reduced neointimal hyperplasia [84]. The antioxidant-mediated inhibition of nuclear factor k B (NFkB) and the subsequent non selective reduction of cytokine transcription have been suggested to be responsible for these effects [83]. Additionally, quercetin downregulated both phorbol 12-myristate 13-acetate (PMA)- and tumour necrosis factor-a (TNFa)-induced intercellular adhesion molecule-1 (ICAM-1) expression in human endothelial cells [86]. 

Perlman, H., Sata, M., Krasinski, K., Dorai, T., Buttyan, R. and Walsh, K. (2000) Adenovirus-encoded hammerhead ribozyme to Bcl-2 inhibits neointimal hyperplasia and induces vascular smooth muscle cell apoptosis. Cardiovasc. Res., 45, 570-578. 

Arterial restenosis occurs in 30-40% of patients after angioplasty. The dilated vessel subsequently narrows again because of neointimal hyperplasia. We introduced HVJ liposome containing ec-NOS expression vector into injured rat carotid artery [20], At 2 weeks after the transfer, histological analysis revealed a 70% reduction in neointimal area. In contrast, no inhibition of neointima formation was observed in the control vector transfection group. 

Pemirolast Inhibition of smooth muscle cell proliferation and migration Ohsawa (55) Low restenosis and neointimal hyperplasia... 

Gallo et al. (26) was the first who reported animal data showing a significant reduction of neointimal hyperplasia with the venous infusion of rapamycin. 

Optimal stent implantation and new antiplatelet therapy have reduced the thrombotic complication after stent implantation, dramatically. However, thrombosis remains a challenge in some lesions and patient subgroups. As an initial and unavoidable event during stent implantation, thrombosis and platelet activation are also involved in the development of neointimal hyperplasia. Stents coated with heparin and other antithrombotic drugs have been demonstrated to decrease thrombotic complications, although their effect on neointimal hyperplasia remains uncertain. As heparin is attached to the stent surface, we divide thromboresistant stents as heparin-coated stents and drug-eluting thromboresistant stents. 

Drug-eluting stents to decrease neointimal hyperplasia... 

Table 3). Mural thrombi may serve as a scaffold for subsequent cell proliferation and undergo organization. However, early thrombus formation alone is not responsible for the development of neointimal hyperplasia. As discussed earlier, controversial results on neointimal hyperplasia with thromboresistant stents have been reported. 

Inflammatory response after stent implantation plays an important role in the cascade of neointimal formation. A positive correlation between inflammatory reaction and restenosis has been observed (16). Perivasculitis caused by stent deployment also participates in the neointimal formation (17). Corticosteroids, as an anti-inflammatory agent, have been evaluated. Methylprednisolone (MP)-loaded stents with different doses showed a positive dose-related effect on neointimal hyperplasia (18). Furthermore, MP-coated stents showed decreased macrophages at the stented sites (19). In clinic, dexamethasone-coated stents showed an inhibitive effect on neointimal hyperplasia in selected patients (20), although no beneficial effect was observed in a randomized trial compared to bare stents (21). For other type of drugs with anti-inflammatory characteristics, such as ibuprofen, colchicine, aton/astatin, and probucol, no favorable effects on neointimal hyperplasia were observed (18,22,23). 

De Scheerder I, Szilard M, Huang Y et al, Evaluation of the effect of oversizing on vascular injury, thrombogenicity and neointimal hyperplasia using the Magic Wallstent in a porcine coronary model [abstr], JACC 2000 35(2) 70A. 

Huang Y Salu K, Wang L, et al. Use of a tacrolimus-eluting stent to inhibit neointimal hyperplasia in a porcine coronary model, J Invasive Cardiol 2005 17(3) 142-148. 

Hong MK, Komowski R, Bramwell O, et al. Paclitaxel-coated gianturco-roubin II (GR II) stents reduce neointimal hyperplasia in a porcine coronary in-stent restenosis model. Coron Artery Dis 2001 12(6)513-515. 

Heldman AW, Cheng L, Jenkins GM, et al. Paclitaxel stent coating inhibits neointimal hyperplasia at 4 weeks in a porcine model of coronary restenosis. Circulation 2001 103( 18) 2289-2295. 

Serruys PW, Sianos G, Abizaid A, et al. The effect of variable dose and release kinetics on neointimal hyperplasia using a novel paclitaxel-eluting stent platform the Paclitaxel In-Stent Controlled Elution Study (PISCES). J Am Coll Cardiol 2005 46(2) 253-260. 

As described earlier, selection of the appropriate CDD mechanism depends on the application and the nature of the drug to be delivered, The development of DES was centered on addressing the issue of restenosis occurring secondary to neointimal hyperplasia, which was the major limiting factor after BMS implantation (16-20). 

Restenosis is caused by an exaggerated healing response involving smooth-muscle migration, neointimal hyperplasia, and a lack of compensatory vessel wall dilation, which result in a reduced vessel luminal diameter at the site of previous endothelial trauma or injury (12-14). Therefore, ICB attempts to attenuate this process and reduce target-vessel restenosis and repeat revascularization. 

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