Smooth muscle proliferation

Mecfianism of Action A prostaglandin that dilates systemic and pulmonary arterial vascular beds, alters pulmonary vascular resistance, and suppresses vascular smooth muscle proliferation. Therapeutic Effect Improves symptoms and exercise tolerance in patients with pulmonary hypertension delays deterioration of condition. Pharmacokinetics Protein binding 60%. Metabolized in liver. Primarily excreted in urine minimal elimination in feces. Half-life 20-30 min. 

To provide optimal immunosuppressant effects, sirolimus is typically combined with glucocorticoids or other immunosuppressants. Sirolimus exerts a number of other beneficial effects, including the ability to inhibit smooth muscle proliferation in blood vessel walls. For this reason, sirolimus is sometimes incorporated into drug-eluting stents that is, a supportive tubular structure (stent) is placed in the lumen of a partially occluded artery, and the drug is released slowly from the stent to help reduce vessel occlusion.64... 

LAM and Other Diseases Characterized by Smooth Muscle Proliferation, edited by J. Moss... 

Carmody et al. found that the addition of homocysteine to a culture of vascular smooth muscle cells resulted in a dose-dependent increase in DNA synthesis and cell proliferation, but vitamins B6 and B 2 alone did not substantially inhibit the effect of homocysteine. However, the addition of folic acid resulted in significant inhibition of DNA synthesis (64). Rosiglitazone has been shown to reduce serum tHcy levels, smooth muscle proliferation, and intimal hyperplasia in Sprague-Dawley rats fed a diet high in methionine (65). 

Is homocysteine involved in the pathogenesis of restenosis An association between homocysteine and restenosis is not unlikely, given the fact that homocysteine appears to induce inflammation, impair endothelial function, and stimulate smooth muscle proliferation all these mechanisms are potentially implicated in the development of restenosis. However, the data regarding tHcy levels and the risk of restenosis after coronary angioplasty are conflicting. Some investigators found an increased risk of restenosis after PCI in patients with high plasma levels of homocysteine, especially in patients not treated with stents (70-72), whereas others did not find any increased risk either in patients with (73-75) or without stents (76). 

Murthy SN, et al. Rosiglitazone reduces serum homocysteine levels, smooth muscle proliferation, and intimal hyperplasia in Sprague-Dawley rats fed a high methionine diet. Metabolism 2005 54 5) 645-652. 

Cilostazol is a phosphodiesterase inhibitor that reduces platelet aggregation, vascular smooth muscle proliferation and also has vasodilatory effects. Earlier studies comparing cilostazol and aspirin to ticlodipine and aspirin identified no significant increase in the subacute stent thrombosis rate (21-23). Indeed, the latter has been supported by comparison of this combination to clopidogrel and aspirin (24). Two recent trials, however, have demonstrated that a much higher proportion of patients develop subacute stent thrombosis when taking cilostazol as compared with ticlodipine (25,26). The data from these trials are summarized in Table I. 

Smith PG, Janiga KE, Bruce MC. Strain increases airway smooth muscle proliferation. Am J Respir Cell Mol Biol. 1994 10 85-90. 

Although activation of cGMP production inhibits vascular smooth muscle proliferation (Itoh et /., 1990 Winter, 1993), no comparable effect of cGMP has been demonstrated in ASM. 

Panettieri, R.A., Rubinstein, N.A., Feuertein, N. and Kotlikoff, M.I. (1991). Beta-adrenergic inhibition of airway smooth muscle proliferation. Am. Respir. Dis. 143, A608. 

Atherosclerosis. A type of arteriosclerosis that is characterized by atheroma formation. It is a multifactorial process leading to the accumulation of lipids within the vessel wall, associated with mononuclear cell infiltration and smooth muscle proliferation. Autoimmune-mediated inflammation may play an important role in accelerated atherosclerosis in autoimmune rheumatic diseases. 

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