Plasminogen treatment of conditions associated with PAI-1 overexpression

1. A method for preventing, slowing progression of, or treating, a disease or a condition in a non-plasminogen-deficient subject, wherein said disease or condition is associated with an overexpression of PAI-1, wherein the method comprises:

a) detecting the PAI-1 level in a blood sample or an injured tissue sample of the subject to determine the overexpression of PAI-1 in the subject, and

b) administering an effective amount of plasminogen, a variant thereof or an analog thereof to the subject to down-regulate their expression of PAI-1 and prevent, slow the progression of, or treat the disease or condition.

2. The method of claim 1 , wherein said disease or a condition associated with an overexpression of PAI-1 is a disease associated with an impaired vascular or tissue remodeling capacity, or a metabolic or hormonal disorder.

3. The method of claim 2 , wherein the disease associated with an impaired vascular or tissue remodeling capacity is chronic renal disease, glomerulosclerosis, fibrosis, tubulointerstitial fibrosis, glomerulonephritis, atherosclerosis, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, chronic kidney disease (CKD), membranous nephropathy, or chronic allograft nephropathy.

4. The method of claim 3 , wherein the disease is a pulmonary fibrosis.

5. The method of claim 4 , wherein plasminogen, a variant thereof or an analog thereof, is used in combination with an antifibrotic agent.

6. The method of claim 5 , wherein the antifibrotic agent is pirfenidone.

7. The method of claim 2 , wherein the metabolic or hormonal disorder is obesity, polycystic ovarian disease, amyloidosis, alopecia, or aging.

8. The method of claim 4 , wherein the pulmonary fibrosis is idiopathic pulmonary fibrosis.

9. The method of claim 1 , wherein the subject has a plasmatic plasminogen activity that is greater than 70% of a normal plasminogen activity level.

10. The method of claim 1 , which is used for slowing progression of, or treating, a disease or a condition associated with an overexpression of PAI-1 in a non-plasminogen-deficient subject.

11. The method of claim 1 , comprising administering plasminogen to the subject.

12. A method for down-regulating PAI-1 expression in an injured tissue of a subject, wherein said method comprises:

a) detecting the PAI-1 level in the injured tissue of the subject to determine the overexpression of PAI-1, and

b) administering an effective amount of plasminogen, a variant thereof or an analog thereof to the subject to down-regulate their expression of PAI-1.

13. The method of claim 12 , wherein the subject has a plasmatic plasminogen activity that is greater than 70% of a normal plasminogen activity level.

14. The method of claim 12 , comprising administering plasminogen to the subject.

15. A method for slowing progression of or treating pulmonary fibrosis in a subject having pulmonary fibrosis, wherein the method comprises:

a) detecting a PAI-1 level in a blood sample or injured lung tissue of the subject to determine the overexpression of PAI-1 in the subject, and

b) administering an effective amount of plasminogen, a variant thereof or an analog thereof to the subject to down-regulate their expression of PAI-1 and prevent, slow the progression of, or treat their pulmonary fibrosis.

16. The method of claim 15 , wherein plasminogen, a variant thereof or an analog thereof, is used in combination with an antifibrotic agent.

17. The method of claim 16 , wherein the antifibrotic agent is pirfenidone.

18. The method of claim 15 , wherein the subject has a plasmatic plasminogen activity that is greater than 70% of a normal plasminogen activity level.

19. The method of claim 15 , wherein the pulmonary fibrosis is idiopathic pulmonary fibrosis.

20. The method of claim 15 , comprising administering plasminogen to the subject.