Methods of inhibition of stenosis and/or sclerosis of the aortic valve

• US 20040057955A1
• Filed: 11/24/2003
• Published: 03/25/2004
• Est. Priority Date: 10/05/2001
• Status: Abandoned Application

• Current Assignee: Washington University In St Louis
• Original Assignee: Washington University In St Louis
• Inventors: Probstfield, Jeffrey L., OʼBrien, Kevin D., Otto, Catherine M.
• Application Number:
  US10/398,492
• Publication Number:
  US 20040057955A1
• Time in Patent Office: Days
• US Class Current: 424/146.1
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/366 having six-membered rings, e.g. delta-lactones
• CPC Class Codes: A61K 31/401 Proline; Derivatives thereof, e.g. captopril

Abstract

The present invention provides methods for decreasing the amount and/or biological activity of angiotensin II in an aortic valve in an animal. The methods of the invention include administering to the animal an amount of an angiotensin converting enzyme antagonist and/or an angiotensin II type 1 receptor antagonist, effective to decrease the amount and/or biological activity of angiotensin II in the aortic valve in the animal.

Claims

1. A method of decreasing the amount and/or biological activity of angiotensin II in an aortic valve in an animal, comprising administering to the animal an amount of an angiotensin II inhibiting agent, selected from the group consisting of angiotensin converting enzyme antagonists and angiotensin II type 1 receptor antagonists, effective to decrease the amount and/or biological activity of angiotensin II in the aortic valve in the animal.

2. The method of claim 1 wherein the angiotensin II inhibiting agent is an antagonist of angiotensin converting enzyme.

3. The method of claim 2 wherein the angiotensin converting enzyme antagonist is a pharmacological agent selected from the group consisting of a pharmaceutical compound that inhibits angiotensin converting enzyme, an antisense angiotensin converting enzyme nucleic acid molecule, an anti-angiotensin converting enzyme antibody, an angiotensin converting enzyme blocking peptide and an angiotensin converting enzyme ribozyme.

4. The method of claim 3 wherein said angiotensin converting enzyme antagonist is selected from the group consisting of ramipril, quinapril, captopril, lisinopril, benazepril, enalapril and fosinopril.

5. The method of claim 2 wherein said angiotensin converting enzyme antagonist is effective to decrease the amount and/or biological activity of angiotensin converting enzyme carried into the aortic valve by low density lipoproteins.

6. The method of claim 5 wherein said angiotensin converting enzyme antagonist is a pharmaceutical compound that decreases plasma low density lipoprotein levels in the animal.

7. The method of claim 6 wherein said pharmaceutical compound is selected from the group consisting of statin, lovastatin, pravastatin, simvastatin, atorvastatin, rosuvastatin;

nicotinic acid, bile acid binding resins, fibric acid derivatives and cholesterol adsorption inhibitors.

8. The method of claim 5 wherein said angiotensin converting enzyme antagonist is a molecule that inhibits binding and/or retention of angiotensin converting enzyme-containing low density lipoprotein particles in an aortic valve lesion.

9. The method of claim 1 wherein a angiotensin II type 1 receptor antagonist is introduced into the animal.

10. The method of claim 9 wherein said angiotensin II type 1 receptor antagonist is a pharmacological agent selected from the group consisting of a pharmaceutical compound, an antisense angiotensin II type 1 receptor nucleic acid molecule, an anti-angiotensin II type 1 receptor antibody, an angiotensin II type 1 receptor blocking peptide and an angiotensin II type 1 receptor ribozyme.

11. The method of claim 10 wherein said pharmaceutical compound is selected from the group consisting of losartan, valsartan, irbesatan, telmesartan and candesartan.

12. The method of claim 1 wherein the animal is exhibiting aortic valve disease, and the amount of the introduced agent is effective to prevent progression and/or complications of aortic valve disease.

13. The method of claim 12 wherein the aortic valve disease is aortic sclerosis.

14. The method of claim 12 wherein the aortic valve disease is aortic stenosis.

15. The method of claim 1 wherein the agent is introduced into the animal by a method selected from the group consisting of injection, transdermal application and as a component of a lipid complex.

16. The method of claim 15 further comprising a plurality of angiotensin II antagonist molecules, specific for the inhibition of angiotensin converting enzyme and/or angiotensin II type 1 receptor that are introduced into the animal.