Treatment of vascular injury using vascular endothelial growth factor

• US 5,830,879 A
• Filed: 10/02/1995
• Issued: 11/03/1998
• Est. Priority Date: 10/02/1995
• Status: Expired due to Fees

• Current Assignee: Steward Research And Specialty Projects Corporation
• Original Assignee: St. Elizabeth'S Medical Center Of Boston, Inc.
• Inventors: Isner, Jeffrey M.
• Primary Examiner(s): Stanton, Brian R.
• Assistant Examiner(s): MARTIN, JILL D
• Application Number:
  US08/538,301
• Time in Patent Office: 1,128 Days
• Field of Search: 514/44, 435/320.1, 435/69.4, 435/69.6, 435/69.8, 435/91.2, 435/172.3, 536/23.5, 536/23.51
• US Class Current: 514/44.00R
• CPC Class Codes: A61K 38/1866 Vascular endothelial growth factor [VEGF]
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C07K 14/52 Cytokines; Lymphokines; Interferons

Abstract

The present invention provides a method for inducing reendothelialization of the lining of an injured blood vessel comprising contacting the injured portion of the vessel with nucleic acid encoding an endothelial cell mitogen such as vascular endothelial growth factor (VEGF) operably linked to a promoter to result in expression of the mitogen when delivered to the cells at the site of vascular injury. The resulting reendothelialization of the injured blood vessel inhibits smooth muscle cell proliferation and consequently reduces restenosis. The methods of the present invention may be used to treat any blood vessel injury that results in denuding of the endothelial lining of the vessel wall, including, for example, those injuries resulting from balloon angioplasty and deployment of endovascular stents.

Claims

1. A method for inducing reendothelialization in an injured blood vessel in a human host, wherein said injured blood vessel comprises a denuded portion of its endothelial lining, comprising:

(a) selecting a human host having an injured blood vessel comprising a denuded portion of its endothelial lining;

(b) administering to cells of said injured blood vessel in the human host an effective amount of DNA that encodes vascular endothelial growth factor (VEGF) admixed with an hydrogel polymer; and

(c) expressing the VEGF encoded by said DNA in said cells such that reendothelialization occurs in said denuded portion of said injured blood vessel.

2. The method of claim 1, wherein said blood vessel injury is the result of balloon angioplasty.

3. The method of claim 1, wherein said blood vessel injury is the result of deployment of an endovascular stent.

4. The method of claim 1, further comprising performing balloon angioplasty and wherein said DNA encoding VEGF is administered to said injured blood vessel at the same time as said angioplasty.

5. A method of reducing restenosis in a human host, comprising:

(a) selecting a human host at risk for restenosis resulting from deployment of an endovascular stent in a blood vessel, wherein said deployment results in denuding of a portion of the endothelial lining of said blood vessel;

(b) administering to cells of said blood vessel in the human host an effective amount of DNA that encodes vascular endothelial growth factor (VEGF) admixed with an hydrogel polymer; and

(c) expressing the VEGF encoded by said DNA in said cells such that restenosis in said denuded portion of said blood vessel is reduced.