Restenosis

Hypothesis Systemic Depletion of Macrophages to Prevent Restenosis 

In this chapter, we will review studies on formulation variables affecting monocyte and macrophage targeting (e.g., size and number of vesicles), in vitro characterization in cell cultures, and in vivo immunomodulation and anti-inflammatory responses. 

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Laser ablation systems hold considerable promise if restenosis (reblocking of the arteries) rates are reduced. The rate as of 1995 is 30%, typically within six months. Mechanical or atherectomy devices to cut, shave, or pulverize plaque have been tested extensively in coronary arteries. Some of these have also been approved for peripheral use. The future of angioplasty, beyond the tremendous success of conventional balloon catheters, depends on approaches that can reduce restenosis rates. For example, if appHcation of a dmg to the lesion site turns out to be the solution to restenosis, balloon catheters would be used for both dilating the vessel and deUvering the dmg. An understanding of what happens to the arterial walls, at the cellular level, when these walls are subjected to the various types of angioplasty may need to come first. 

The calcification of atherosclerotic plaques may be induced by osteopontin expression, since osteopontin is a protein with a well-characterized role in bone formation and calcification. Vascular smooth muscle cell migration on osteopontin is dq endent on the integrin av 33 and antagonists of av 33 prevent both smooth muscle cell migration and restenosis in some animal model [8]. 

Due to the pivotal role of platelets in thrombus formation, especially in the arterial system, inhibition of platelet function has become a central pharmacological approach. Antiplatelet drugs are given in order to prevent and treat thromboembolic diseases such as coronary heart disease, peripheral and cerebrovascular disease. They have also revolutionized the procedures of invasive coronary interventions as they reduce the risk of restenosis and thrombosis. 

The PDE3 inhibitor, cilostazol, has been used as an antithrombotic agent and is currently being used in patients being treated for intermittent claudication. Cilostazol is also used for the prevention of restenosis after treatments such as angioplasty. Another PDE3 selective inhibitor, milrinone, has been used in the treatment of congestive heart failure. Milrinone also has been shown to increase the conductance of the CFTR transporter in vitro. 

Restenosis is the phenomenon of vascular reocclusion postangioplasty or stent. 

Orford JL, Selwyn AP, Ganz P, et al (2000) The comparative pathobiology of atherosclerosis and restenosis. Am J Cardiol 86(Suppl) 6H-llH... 

Elevated homocysteine concentrations have been associated with an increased risk for cardiovascular disease in both epidemiologic and clinical studies.43 Several studies have evaluated the benefit of lowering homocysteine levels with folic acid supplementation. One study reported a reduction in major cardiac events with the combination of folic acid, vitamin B12, and vitamin B6 following PCI.44 However, a more recent study found an increased risk of instent restenosis and the need for target-vessel revascularization with folate supplementation following coronary stent placement.45 The role of folate in the management of IHD is currently unclear. 

Percutaneous coronary intervention A minimally invasive procedure whereby access to the coronary arteries is obtained through the femoral artery up the aorta to the coronary os. Contrast media is used to visualize the coronary artery stenosis using a coronary angiogram. A guidewire is used to cross the stenosis and a small balloon is inflated and/or stent is deployed to break up atherosclerotic plaque and restore coronary artery blood flow. The stent is left in place to prevent acute closure and restenosis of the coronary artery. Newer stents are coated with antiproliferative drugs, such as paclitaxel and sirolimus, which further reduce the risk of restenosis of the coronary artery. 

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... 

Cipollone F, Marini M, Fazia M, et al. Elevated circulating levels of monocyte chemoattractant protein-1 in patients with restenosis after coronary angioplasty. Arterioscler Thromb Vase Biol 2001 21(3) 327-334. 

Horvath C, Welt FG, Nedelman M, Rao P, Rogers C. Targeting CCR2 or CD18 inhibits experimental in-stent restenosis in primates inhibitory potential depends on type of injury and leukocytes targeted. Circ Res 2002 90(4) 488 494. 

Initial tests in the rat revealed a high degree of tissue compatibility of Dat-Tyr-Hex derived polymers. More detailed tests are now in progress. In addition, tyrosine derived polymers are currently being evaluated in the formulation of an intracranial controlled release device for the release of dopamine, in the design of an intraarterial stent (to prevent the restenosis of coronary arteries after balloon angioplasty), and in the development of orthopedic implants. The use of tyrosine derived polymers in these applications will provide additional data on the biocompatibility of these polymers. 

A -(4-Chlorobenzyl)-7-substituted-4-oxo-477-pyrimido[l,2- ]pyridazine-3-carboxamides have been claimed as compounds to treat atherosclerosis and restenosis <2004W02004/019933> and as antiviral agents, particularly against herpes viruses <2002W02002/004444>. The 7-substituted-2-phenyl-pyrimido[l,2- ]pyridazin-5-ium-3-olates 99... 

Keywords Tyrphostins, Protein tyrosine, Kinases, JAK-2 EGF, PDGF BCR-ABL, Psoriasis, Papilloma, Restenosis, Leukemia, Lymphoma... 

PDGFR Overexpression and autocrine stimulation. Activation of blood vessel smooth muscle cells in the media Glioblastomas, Restenosis, Atherosclerosis... 

JLompre I would like to present some of our results describing the changes that occur to cells in culture. My concern is primarily with the organization of the SR when vascular smooth muscle cells proliferate in culture. This is of interest because of the importance of smooth muscle cell proliferation in atherosclerosis and restenosis. Freshly dissociated cells or those that have been cultured for just one... 

On the other hand, insufficient NO production also causes serious medical problems. Many diseases such as hypertension, atherosclerosis and restenosis involve a deficiency of NO production. Therefore, a compound that can release NO under specific conditions can be used therapeutically to palliate NO underproduction. In fact, the best known NO donor, glyceryl trinitrate, has been used for over a century to relieve acute attacks of angina pectoris. 

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