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 a mitogen-activated protein kinase (MAPK) 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 a MAPK pathway inhibitor.  
   
   
       4 . The method of  claim 3  wherein the contacting step comprises impregnating or coating the synthetic graft with a therapeutically effective amount of a MAPK 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 a MAPK 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 a MAPK 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 a MAPK 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 a mitogen-activated protein kinase (MAPK) 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 a MAPK 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 patient comprising contacting a synthetic graft with a therapeutically effective amount of a MAPK pathway inhibitor.  
   
   
       15 . The method of  claim 14  wherein the contacting step comprises impregnating or coating the synthetic graft with a therapeutically effective amount of a MAPK 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 a MAPK 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 a MAPK pathway inhibitor.  
   
   
       19 . The method according to  claim 18  wherein the MAPK pathway inhibitor is UO126.  
   
   
       20 . A synthetic vascular graft comprising a synthetic graft and a therapeutically effective amount of a MAPK pathway inhibitor.  
   
   
       21 . The synthetic vascular graft of  claim 20  wherein the synthetic graft is impregnated or coated with a therapeutically effective amount of a MAPK pathway inhibitor.  
   
   
       22 . The synthetic vascular graft of  claim 20  further comprising an anti-inflammatory agent.  
   
   
       23 . The synthetic vascular graft according to  claim 20  wherein the MAPK pathway inhibitor is UO126.  
   
   
       24 . An angioplasty balloon catheter comprising a catheter and a therapeutically effective amount of a MAPK pathway inhibitor.  
   
   
       25 . The angioplasty balloon catheter of  claim 24  wherein the angioplasty balloon catheter is impregnated or coated with an effective amount of a MAPK pathway inhibitor.  
   
   
       26 . The angioplasty balloon catheter of  claim 24  further comprising an anti-inflammatory agent.  
   
   
       27 . The angioplasty balloon catheter of  claim 24  wherein the MAPK pathway inhibitor is UO126.  
   
   
       28 . A vascular stent comprising a stent and a therapeutically effective amount of a MAPK pathway inhibitor.  
   
   
       29 . The vascular stent of  claim 28  wherein a vascular stent is impregnated or coated with a therapeutically effective amount of a MAPK pathway inhibitor.  
   
   
       30 . The vascular stent of  claim 28  wherein the MAPK pathway inhibitor is UO126.  
   
   
       31 . The vascular stent of  claim 28  further comprising an anti-inflammatory agent.  
   
   
       32 . (canceled)  
   
   
       33 . The method according to  claim 1 , wherein the MAPK pathway inhibitor is UO126.  
   
   
       34 . The method according to  claim 3 , wherein the MAPK pathway inhibitor is UO126.  
   
   
       35 . The-method according to  claim 6 , wherein the MAPK pathway inhibitor is UO126.  
   
   
       36 . The method according to  claim 7 , wherein the MAPK pathway inhibitor is UO126.  
   
   
       37 . The method according to  claim 8 , wherein the MAPK pathway inhibitor is UO126.  
   
   
       38 . The method according to  claim 10 , wherein the MAPK pathway inhibitor is UO126.  
   
   
       39 . The method according to  claim 12 , wherein the MAPK pathway inhibitor is UO126.  
   
   
       40 . The method according to  claim 14 , wherein the MAPK pathway inhibitor is UO126.  
   
   
       41 . The method according to  claim 17 , wherein the MAPK pathway inhibitor is UO126.