Neointima

Srivatsa SS, Tsao P, Holmes DR et al (1997) Selective av(33 integrin blockade limits neointima hyperplasia and lumen stenosis in stented porcine coronary artery injury in Pig. Cardiovasc Res 36 408-428... 

Finally, it has to be mentioned that LPA also has an intracellular target site, which is the nuclear transcription factor, peroxisome proliferator-activated receptor-y (PPARy). LPA competes for thiazolidinedione binding and activates PPARy-dependent gene transcription. Thereby, LPA induced neointima formation in a rat carotid artery model. 

Restenosis after angioplasty is a situation where these therapies may find an early application. The current animal models evaluate the formation of atherosclerosis or a neointima in the same accelerated and artificially induced... 

Schober A, Manka D, von HP, et al. Deposition of platelet RANTES triggering monocyte recruitment requires P-selectin and is involved in neointima formation after arterial injury. Circulation 2002 106(12) 1523-1529. 

Savolainen-Peltonen H, Luoto NM, Kangas L, Hayry P (2004) Selective estrogen receptor modulators prevent neointima formation after vascular injury. Mol Cell Endocrinol 227 9-20... 

The rat carotid artery injured by a balloon catheter has been widely used as a model of angioplasty. The rat model is a proliferation model without foam cells (93). This form of injury causes immediate coagulation and thrombosis cascade in which platelets adhere, spread, and degranulate on the denuded surface of the artery, and approximately 24 hours later SMC begin to proliferate. Liposomal BPs, clodronate, and alendronate were injected to male sabra rats, 15 and 3mg/kg, respectively (52,69,76). Marked neointimal formation and decreased luminal area were observed in control animals. Neointima/media (N/M) ratio was 1.3 0.2, and luminal stenosis was 44 3%. LC and LA suppressed intimal growth when administered intravenously on day -1 and day 6. N/M ratios were reduced by 60% and 69% for LC and LA, respectively. 

Fukuda D, Shimada K, Tanaka A, Kawarabayashi T, Yoshiyama M, Yoshikawa J. Circulating monocytes and in-stent neointima after coronary stent implantation. J Am Coll Cardiol 2004 43 18-23. 

Strehlow K, Werner N, Berweiler J, Link A, Dimagl U, Priller J, Laufs K, Ghaeni L, Milosevic M, Bohm M, Nickenig G. Estrogen increases bone marrow-derived endothelial progenitor cell production and diminishes neointima formation. Circulation 2003 107 3059-3065. 

Tulis DA, Mnjoyan ZH, Schiesser RL, et al. Adenoviral gene transfer of fortilin attenuates neointima formation through suppression of vascular smooth muscle cell proliferation and migration. Circulation. Jan 7 2003 107(1) 98-105. 

E. Chignier, J. Guidollet, Y. Heynen, M. Serres, G. Clendinnen, P. Louisot, R. Eloy, Macromolecular, histological, ultrastructural and immunocytochemical characteristics of the neointima developed within PTFE vascular grafts. Experimental study in dogs, J. Biomed. Mater. Res. 17(4) (1983) 623-636. 

Carotid artery thickening effect. Policosanol was administered to rabbits with collars around the left carotid at doses of 5 and 25 mg/kg for 7 and 15 days or 20 mg/kg lovastatin for 15 days. There was a significant reduction in neointima in the treated animals compared with controls. The reduction in lovastatin-treated animals was sig-... 

Adenoviruses carrying the gene that expresses TIMP-3 has been shown to be able to overexpress TIMP3 within the extracellular matrix. As a result MMP activity was decreased and apoptosis levels in the neointima and medial layer were significantly elevated by TIMP-3 overexpression. Consequently neointimal formation declined by 84% in human veins at 14 days and by 58% in pig vein grafts. 

George, S.J., C.T. Lloyd, G.D. Angehni,A.C. Newby, and A.H. Baker, Inhibition of late vein graft neointima formation in human and porcine models by adenovirus-mediated overexpression of tissue inhibitor of metalloproteinase-3. Circulation, 2000.101(3) 296-304. 

A biologic surface that develops an endothelial cell surface is referred to as a neointima. If it is covered with blood components such as fibrin, it is called a pseudointima. In both cases, the surfaces are passive with respect to the blood to which they come into contact. A pseudointima, however, is typically unstable and subject to further ihrombic response. If the surface is damaged, as during surgical implantation, a catastrophic failure can result. This coupled with the difficulty of developing a complete endothelial layer caused one researcher to describe a device as physiologically tolerable rather than biocompatible or hemocompatible. 

Cayatte AJ, Palacino JJ, Horten K, Cohen RA. 1994. Chronic inhibition of nitric oxide production accelerates neointima formation and impairs endothelial function in hypercholesterolemic rabbits. Arterioscler Thromb Vase Biol 14 753-759. 

The effects of VEGFs are at least partially mediated by the enhanced production of NO and prostacyclin (Laitinen et al., 1997b Zachary, 1998). Furthermore, in addition to endothelial cell proliferation and inhibition of neointima formation, VEGF-A may also lead to neoangiogenesis in ischemic tissues... 

Lipskaia, L., del Monte, F., Capiod, T., Yacoubi, S., Hadri, L., Hours, M., Hajjar, R. J. and Lompre, A. M., 2005, Sarco/endoplasmic reticulum Ca2+-ATPase gene transfer reduces vascular smooth muscle cell proliferation and neointima formation in die rat. Circ Res 97, 488—95. 

Several decades ago, two studies showed that, as compared to dense vascular grafts, porous grafts enhanced the formation of a stable neointima as well as the growth of... 

Kusaba A, Fischer 3rd CR, Matulewski TJ, Matsumoto T. Experimental study of the influence of porosity on development of neointima in Gore-Tex grafts a method to increase long-term patency rate. American Surgeon 1981, 47, 347-354. 

Watanabe T. Experimental study on the influence of porosity on the development of the neointima in E-PTFE grafts. Nippon Geka Gakkai Zasshi 1984, 85, 580-591. 

Dacron, however, continues to he the most popular material used in the production of artificial blood vessels. When first used with experimental animals, treated Dacron appeared to induce the regeneration of interior walls of blood vessels (called neointima) in essentially the same way as the natural process. When implanted into humans, however, the same treated Dacron has a somewhat different effect, resulting instead in the formation of a thin (about 1 mm thick) layer of fibrin (or a pseudointima) on the inner lining of the blood vessel. While this thin layer of fibrin is of relatively modest concern in larger blood vessels, it can be a serious problem in vessels less than 5 mm in diameter. In such cases, fibroblasts from the blood stream attach themselves to the fibrin, and the blood vessel gradually becomes blocked. 

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. 

The results of the one-year experimental investigations confirm the results of the four-week studies. The integration processes are in progress. The homogeneity and the neointima anchorage capability correspond with the recipient blood vessel, the carotid artery of the rat. The detected collagen confirms vital fibroblasts and these induce an increased integration of BASYC . 

The endothelial cells assume their entire function in the neointima. In all one-year animals (N = 5) no thrombosis was recognized. 

The simplest answer is ease of administration. More importantly, there are several limitations to local delivery of drugs in the form of DES. The efficacy of these new devices depends on several variables, including the selection of an effective drug, its solubility, diffusion characteristics, release kinetics, arterial tissue concentration, retention, and whether the platform is polymer based or nonpolymeric. Local delivery of the drug in this manner may delay rather than prevent neointima. This is supported by preclinical studies that show impaired healing and neointimal catch-up (4). There is concern that neointimal growth will accelerate in response to the... 

Phillips JW, Barringhaus KG, Sanders JM, et al. Rosiglitazone Reduces the Accelerated Neointima Formation After Arterial Injury in a Mouse Injury Model of Type 2 Diabetes Circulation 2003 108 1994-1999. 

Marx N, Wohrle J, Nusser T et al. Pioglitazone reduces neointima volume after coronary stent implantation a randomized, placebo-controlled, double-blind trial in nondiabetic patients. Circulation 2005 I 12 2792-2798. 

First author (reference) Year Type of stent Polymer Model Control Thrombosis reduction Neointima reduction... 

Abbreviations CEL, cellulose CHC, chlorohydrocarbon GP, glycoprotein GR. gianturco-roubin NA, not available Neo-R, neointima reduction PGI2. prostaglandin I2 PLLA(PLA), poly-L-lactic acid P-S, Palmaz-Schatz PUR. polyurethane Thr-R, thrombosis reduction. PEG. polyethyleneglycol ... 

Banai S, Gertz SD, Gavish L, et al. Tyrphostin AGL-2043 eluting stent reduces neointima formation in porcine coronary arteries, Cardiovasc Res 2004 64( I) I 65-171,... 

Jaschke B, Michaelis C, Milz S, et al. Local statin therapy differentially interferes with smooth muscle and endothelial cell proliferation and reduces neointima on a drug-eluting stent platform, Cardiovasc Res 2005 68(3) 483-492. 

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