Inhibition of Mitogen-activated Protein Kinases in Cardiovascular Disease

Abstract

The present invention relates to methods for inhibiting subacute thrombosis and/or intimal hyperplasia following an interventional vascular procedure by contacting a blood vessel or a synthetic material with a mitogen-activated protein kinase (MAPK) pathway inhibitor. The present invention further relates to vascular devices comprising a MAPK pathway inhibitor.

1 . A method for decreasing the incidence of subacute thrombosis in a patient, which method comprises contacting an exposed vein to be used for grafting with a therapeutically effective amount of an ERK1/2 pathway inhibitor prior to vein excision. 
     
     
         2 . The method of  claim 1 , wherein the contacting step further comprises contacting the exposed vein with an anti-inflammatory agent. 
     
     
         3 . A method for decreasing the incidence of subacute thrombosis in a patient, which method comprises contacting a synthetic graft with a therapeutically effective amount of an ERK1/2 pathway inhibitor. 
     
     
         4 . The method of  claim 3 , wherein the contacting step comprises impregnating or coating the synthetic graft with the ERK1/2 pathway inhibitor. 
     
     
         5 . The method of  claim 3 , wherein the contacting step further comprises contacting the synthetic graft with an anti-inflammatory agent. 
     
     
         6 . A method for decreasing the incidence of subacute thrombosis in a patient, which method comprises contacting an angioplasty balloon catheter with a therapeutically effective amount of an ERK1/2 pathway inhibitor. 
     
     
         7 . A method for decreasing the incidence of subacute thrombosis in a patient, which method comprises contacting a stent with a therapeutically effective amount of an ERK1/2 pathway inhibitor. 
     
     
         8 . A method for decreasing the incidence of subacute thrombosis in a patient, which method comprises contacting an excised vein to be used for grafting with an ERK1/2 pathway inhibitor. 
     
     
         9 . The method of  claim 8 , which further comprises contacting the excised vein with an anti-inflammatory agent. 
     
     
         10 . A method for decreasing the incidence of intimal hyperplasia in a patient, which method comprises contacting an exposed vein to be used for grafting with a therapeutically effective amount of an ERK1/2 pathway inhibitor prior to vein excision. 
     
     
         11 . The method of  claim 10  further comprising contacting the exposed vein with an anti-inflammatory agent. 
     
     
         12 . A method for decreasing the incidence of intimal hyperplasia in a patient, which method comprises contacting an excised vein to be used for grafting with a therapeutically effective amount of an ERK1/2 pathway inhibitor. 
     
     
         13 . The method of  claim 12 , which further comprises contacting the excised vein with an anti-inflammatory agent. 
     
     
         14 . A method for decreasing the incidence of intimal hyperplasia in a patient, which method comprises contacting a synthetic graft with a therapeutically effective amount of an ERK1/2 pathway inhibitor. 
     
     
         15 . The method of  claim 14 , wherein the contacting step comprises impregnating or coating the synthetic graft with the ERK1/2 pathway inhibitor. 
     
     
         16 . The method of  claim 14 , which further comprises contacting the synthetic graft with an anti-inflammatory agent. 
     
     
         17 . A method for decreasing the incidence of intimal hyperplasia in a patient, which method comprises contacting an angioplasty balloon catheter with an effective amount of an ERK1/2 pathway inhibitor. 
     
     
         18 . A method for decreasing the incidence of intimal hyperplasia in a patient, which method comprises contacting a stent with an effective amount of an ERK1/2 pathway inhibitor. 
     
     
         19 . The method according to  claim 18 , wherein the ERK1/2 pathway inhibitor is UO126. 
     
     
         20 - 31 . (canceled) 
     
     
         32 . A method for preventing subacute thrombosis or intimal hyperplasia in a patient, which method comprises contacting a suture with an ERK1/2 pathway inhibitor. 
     
     
         33 . A method for reducing intimal hyperplasia in an artery of a patient, which method comprises: (a) contacting a vascular stent with an ERK1/2 pathway inhibitor prior to stent implantation into the artery, and (b) implanting the stent into the artery of the patient so that the artery is transiently exposed to a therapeutically effective amount of the ERK1/2 pathway inhibitor, wherein said transient exposure provides long-term inhibition of intimal hyperplasia in the artery.