Claims
- 1-48. (canceled).
- 49. A method for inducing new blood vessel growth in myocardial tissue of a mammal in need of such treatment comprising:
a) injecting an effective amount of a solution comprising a nucleic acid encoding at least one angiogenic protein or an effective fragment thereof into the myocardial tissue; and b) administering to the mammal an effective amount of at least one angiogenic factor or an effective fragment thereof, thereby inducing the new blood vessel growth in the myocardial tissue of the mammal.
- 50. The method of claim 49, wherein the angiogenic factor is a vascular endothelial growth factor (VEGF) or an effective fragment thereof.
- 51. The method of claim 50, wherein the VEGF is VEGF-1 or VEGF165.
- 52. The method of claim 49, further comprising expressing the angiogenic protein or fragment in the myocardium.
- 53. The method of claim 52, wherein the method further comprises increasing frequency of endothelial progenitor cells (EPC) in the mammal.
- 54. The method of claim 53, wherein the increase in frequency of the EPC is at least about 20% as determined by a standard EPC isolation assay.
- 55. The method of claim 49, wherein the method further comprises increasing EPC differentiation in the mammal.
- 56. The method of claim 55, wherein the increase in EPC differentiation is at least about 20% as determined by a standard EPC culture assay or a standard hindlimb ischemia assay.
- 57. The method of claim 50, wherein the level of VEGF or VEGF fragment expression is sufficient to increase neovascularization by at least about 5% as determined by a standard cornea micropocket assay.
- 58. The method of claim 49, wherein the amount of administered angiogenic factor such as SCF, CSF or fragment is sufficient to increase EPC bone marrow derived EPC incorporation into foci.
- 59. The method of claim 58, wherein the increase in EPC bone marrow derived EPC incorporation into foci is at least about 20% as determined by a standard rodent bone marrow (BM) transplantation model.
- 60. The method of claim 49, wherein the method further comprises administering at least one angiogenic protein or effective fragment thereof before or after administration of the nucleic acid to the mammal.
- 61. The method of claim 49, wherein the method further comprises administering to the mammal an anti-coagulant before, during, or after administration of the nucleic acid to the mammal.
- 62. The method of claim 61, wherein the anti-coagulant is one or more of urokinase, plasminogen activator, and heparin.
- 63. The method of claim 49, wherein the nucleic acid is directly injected with a catheter or stent.
- 64. The method of claim 49, wherein the nucleic acid is inserted into a cassette operably linked to a promoter.
- 65. The method of claim 49, wherein the myocardial tissue is ischemic or is associated with infarction or dysfunction.
- 66. The method of claims 49, wherein the method further comprises monitoring at least one cardiac function.
- 67. The method of claim 66, wherein the monitored cardiac function is at least one of echocardiography, ventricular end-diastolic dimension (LVEDD), end-systolic dimension (LVESD), fractional shortening (FS), wall motion score index (WMSI), NOGA, cardiac angiography and LV systolic pressure (LVSP).
- 68. The method of claim 49, wherein the angiogenic protein or factor is one of acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF-1), VEGF165, epidermal growth factor (EGF), transforming growth factor α and β (TGF-α and TFG-β), platelet-derived endothelial growth factor (PD-ECGF), platelet-derived growth factor (PDGF), tumor necrosis factor α (TNF-α), hepatocyte growth factor (HGF), insulin like growth factor (IGF), erythropoietin, colony stimulating factor (CSF), macrophage-CSF (M-CSF), granulocyte/macrophage CSF (GM-CSF), stem cell factor (SCF), angiopoetin-1 (Ang1), nitric oxidesynthase (NOS); or a mutein or fragment thereof.
CROSS REFERENCE TO RELATED APPLICATION
[0001] The present application is a continuation-in-part of U.S. Ser. No. 09/265,041 as filed on Mar. 9, 1999 which application claims priority to U.S. Provisional Application No. 60/077,262 as filed on Mar. 9, 1998. The disclosures of the U.S. Ser. No. 09/265,041 and 60/077,262 applications are hereby incorporated by reference.
STATEMENT OF GOVERNMENT INTEREST
[0002] Funding for the present invention was provided in part by the Government of the United States by virtue of grants HL 40518, HL02824 and HL57516 by the National Institutes of Health. Accordingly, the Government of the United States has certain rights in and to the invention claimed herein.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60077262 |
Mar 1998 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
09265041 |
Mar 1999 |
US |
Child |
10696391 |
Oct 2003 |
US |